Search results for: constitutional democracy

Authors: Nourah Almulhim

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This paper takes a critical discourse analysis (CDA) approach to investigate discourse and ideology in political blogs, focusing in particular on the Conservative Home blog from the UK’s current governing party. The Conservative party member’s discourse strategies as the blogger, alongside the discourse used by members of the public who reply to the blog in the below-the-lines comments, will be examined. The blog discourse reflects the writer's political identity and authorial voice. The analysis of the below-the-lines comments enables members of the public to engage in creating adversative positions, introducing different language users who bring their own individual and collective identities. These language users can play the role of news reporters, political analysts, protesters or supporters of a specific agenda and current socio-political topics or events. This study takes a qualitative approach to analyze the discriminatory context towards Islam/Muslims in ' The Conservative Home' blog. A cognitive approach is adopted and an analysis of dominant discourses in the blog text and the below-the-line comments is used. The focus of the study is, firstly, on the construction of self/ collective national identity in comparison to Muslim identity, highlighting the in-group and out-group construction. Second, the type of attitudes, whether feelings or judgments, related to these social actors as they are explicated to draw on the social values. Third, the role of discursive strategies in justifying and legitimizing those Islamophobic discriminatory practices. Therefore, the analysis is based on the systematic analysis of social actors drawing on actors, actions, and arguments to explicate identity construction and its development in the different discourses. A socio-semantic categorization of social actors is implemented to draw on the discursive strategies in addition to using literature to understand these strategies. An appraisal analysis is further used to classify attitudes and elaborate on core values in both genres. Finally, the grammar of othering is applied to explain how discriminatory dichotomies of 'Us' Vs. ''Them' actions are carried in discourse. Some of the key findings of the analysis can be summarized in two main points. First, the discursive practice used to represent Muslims/Islam as different from ‘Us’ are different in both genres as the blogger uses a covert voice while the commenters generally use an overt voice. This is to say that the blogger uses a mitigated strategy to represent the Muslim identity, for example, using the noun phrase ‘British Muslim’ but then representing them as ‘radical’ and ‘terrorists'. Contrary to this is in below the lines comments, where a direct strategy with an active declarative voice is used to negatively represent the Muslim identity as ‘oppressors’ and ‘terrorists’ with no inclusion of the noun phrase ‘British Muslims’. Second, the negotiation of the ‘British’ identity and values, such as culture and democracy, are prominent in the comment section as being unique and under threat by Muslims, while in the article, these standpoints are not represented.

Keywords: xenophobia, blogs, identity, critical discourse analysis

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Authors: Shelley Zion

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This study examines the longitudinal impact (10 years) of a course for education leaders designed to encourage the development of critical consciousness surrounding issues of equity, oppression, power, and privilege. The ability to resist and challenge oppression across social and cultural contexts can be acquired through the use of transformative pedagogies that create spaces that use the practice of exploration to make connections between pervasive structural and institutional practices and race and ethnicity. This study seeks to extend this understanding by exploring the longitudinal influence of participating in a course that utilizes transformative pedagogies, course materials, exercises, and activities to encourage the practice of exploration of student experiences with racial and ethnic discrimination with the end goal of providing them with the necessary knowledge and skills that foster their ability to resist and challenge oppression and discrimination -critical action- in their lives. To this end, we use the explanatory power of the theories of critical consciousness development, sociopolitical development, and social identity construction that view exploration as a crucial practice in understanding the role ethnic and racial differences play in creating opportunities or barriers in the lives of individuals. When educators use transformative pedagogies, they create a space where students collectively explore their experiences with racial and ethnic discrimination through course readings, in-class activities, and discussions. The end goal of this exploration is twofold: first, to encourage the student’s ability to understand how differences are identified, given meaning to, and used to position them in specific places and spaces in their world; second, to scaffold students’ ability to make connections between their individual and collective differences and particular institutional and structural practices that create opportunities or barriers in their lives. Studies have found the formal exploration of students’ individual and collective differences in relation to their experiences with racial and ethnic discrimination results in developing an understanding of the roles race and ethnicity play in their lives. To trace the role played by exploration in identity construction, we utilize an integrative approach to identity construction informed by multiple theoretical frameworks grounded in cultural studies, social psychology, and sociology that understand social-cultural, racial, and ethnic -identities as dynamic and ever-changing based on context-specific environments. Stuart Hall refers to this practice as taking “symbolic detours through the past” while reflecting on the different ways individuals have been positioned based on their roots (group membership) and also how they, in turn, chose to position themselves through collective sense-making of the various meanings their differences carried through the routes they have taken. The practice of exploration in the construction of ethnic-racial identities has been found to be beneficial to sociopolitical development.

Keywords: political polarization, civic participation, democracy, education

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Authors: Claudio Loconsole, Daniele Leonardis, Antonio Brunetti, Gianpaolo Francesco Trotta, Nicholas Caporusso, Vitoantonio Bevilacqua

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Unfortunately, many people still do not have access to communication, with specific regard to reading and writing. Among them, people who are blind or visually impaired, have several difficulties in getting access to the world, compared to the sighted. Indeed, despite technology advancement and cost reduction, nowadays assistive devices are still expensive such as Braille-based input/output systems which enable reading and writing texts (e.g., personal notes, documents). As a consequence, assistive technology affordability is fundamental in supporting the visually impaired in communication, learning, and social inclusion. This, in turn, has serious consequences in terms of equal access to opportunities, freedom of expression, and actual and independent participation to a society designed for the sighted. Moreover, the visually impaired experience difficulties in recognizing objects and interacting with devices in any activities of daily living. It is not a case that Braille indications are commonly reported only on medicine boxes and elevator keypads. Several software applications for the automatic translation of written text into speech (e.g., Text-To-Speech - TTS) enable reading pieces of documents. However, apart from simple tasks, in many circumstances TTS software is not suitable for understanding very complicated pieces of text requiring to dwell more on specific portions (e.g., mathematical formulas or Greek text). In addition, the experience of reading\writing text is completely different both in terms of engagement, and from an educational perspective. Statistics on the employment rate of blind people show that learning to read and write provides the visually impaired with up to 80% more opportunities of finding a job. Especially in higher educational levels, where the ability to digest very complex text is key, accessibility and availability of Braille plays a fundamental role in reducing drop-out rate of the visually impaired, thus affecting the effectiveness of the constitutional right to get access to education. In this context, the Braille Lab project aims at overcoming these social needs by including affordability in designing and developing assistive tools for visually impaired people. In detail, our awarded project focuses on a technology innovation of the operation principle of existing assistive tools for the visually impaired leaving the Human-Machine Interface unchanged. This can result in a significant reduction of the production costs and consequently of tool selling prices, thus representing an important opportunity for social entrepreneurship. The first two assistive tools designed within the Braille Lab project following the proposed approach aims to provide the possibility to personally print documents and handouts and to read texts written in Braille using refreshable Braille display, respectively. The former, named ‘Braille Cartridge’, represents an alternative solution for printing in Braille and consists in the realization of an electronic-controlled dispenser printing (cartridge) which can be integrated within traditional ink-jet printers, in order to leverage the efficiency and cost of the device mechanical structure which are already being used. The latter, named ‘Braille Cursor’, is an innovative Braille display featuring a substantial technology innovation by means of a unique cursor virtualizing Braille cells, thus limiting the number of active pins needed for Braille characters.

Keywords: Human rights, social challenges and technology innovations, visually impaired, affordability, assistive tools

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Authors: Yobo Opare-Addo

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Ghana came under a military and democratic rule of the same leadership from 1981-2000. These were the Provisional National Defense Council (PNDC), a military government and a democratic government, the National Democratic Congress (NDC) both under the leadership of Flt. Lt. J.J. Rawlings. Meanwhile the year 1985 marked a turning point in the development of the tourism industry in Ghana. Interest in tourism among African governments and for that matter the ‘PNDC cum NDC Government’ (PNDC/NDC) arose because of adverse developments in intangible exports and a corresponding decline in commodity export earnings. The ‘PNDC/NDC Government’ undertook measures and policies to improve the tourism industry and at the same time embarked on export diversification to reap the foreign exchange that the industry could generate in Ghana. The objective of this paper is to examine the measures and policies of the PNDC/NDC to improve the tourism industry in order to reap the foreign exchange. It specifically interrogates the role of the government as an agent of tourism development, through its deliberate creation of a conducive environment for tourism to flourish, the involvement of the private sector both foreign and local and the provision of tourism facilities and infrastructure and how these factors impacted on the tourism industry in Ghana. In the final analysis it evaluates the degree of success of the PNDC/NDC Government in this arena of Ghana’s socio-cultural and economic development. Introduction The Provisional National Defense Council (PNDC), a military government under the leadership of Flt. Lt J.J. Rawlings overthrew a constitutionally elected government of People’s National Party in 1981. In 1992, the National Democratic Congress (NDC) won the general election conducted in December. Flt. Lt. J.J. Rawlings, the party’s leader became the President of the Fourth Republic from January 1993 to December 2000. It was refreshing to see Ghanaians embrace democracy with renewed energy, zeal, and enthusiasm. This paper takes a critical look at the efforts of the PNDC cum NDC Government (PNDC/NDC) to develop tourism in Ghana during the period from 1981-2000 Methodology: Qualitative method of research was adopted for the study. Data was collected from both primary and secondary sources, and analysis was done using descriptive analysis because descriptive analysis made it possible to describe or summarize the statistical data in the research. To gather data from primary sources, questionnaires, oral interviews, and semi-structured discussions were conducted. Respondents included public officials from Ghana Tourist Board, Ministry of Tourism, Hoteliers, restaurant operators and travel and tour operators in Accra. Secondary data sources included articles in journals, reports, magazines, bulletins, and books. The major findings included statistical data for tourism arrivals and receipts during the period and the status of the industry by the year 2000. Conclusion: The paper contributes to knowledge on political and historical aspects of tourism development in Ghana, which is almost non-existent, attitudes of the PNDC cum NDC government towards tourism development and the debates on the generation of foreign exchange to Ghana and third world countries.

Keywords: ghana, infrastructure, policies, privatization, tourism facilities

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Authors: Shierwin Agagen Cabunilas

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The unitary form of Philippine government has built a tradition of bureaucracy that strengthened oligarch and clientele politics. Consequently, the Philippines is lagged behind development. There is so much poverty, unemployment, and inadequate social services. In addition, it seems that the rights of national ethnic minority groups like the Igorots to develop their political and economic interests, linguistic and cultural heritage are neglected. Given these circumstances, a paradigm shift is inevitable. The author advocates a transition from a unitary to a federal system of government. Contrary to the notion that a unitary system facilitates better governance, it actually stifles it. As a unitary government, the Philippines seems (a) to exhibit incompetence in delivering efficient, necessary services to the people and (b) to exclude the minority from political participation and policy making. This shows that Philippine unitary system is highly centralized and operates from a top-bottom scheme. However, a federal system encourages decentralization, plurality and political participation. In my view, federalism is beneficial to the Philippine society and congenial to the Igorot indigenous peoples insofar as participative decision-making and development goals are concerned. This research employs critical and constructive analyses. The former interprets some complex practices of Philippine politics while the latter investigates how theories of federalism can be appropriated to deal with political deficits, ethnic diversity, and indigenous peoples’ rights to self-determination. The topic is developed accordingly: First, the author briefly examines the unitary structure of the Philippines and its impact on inter-governmental affairs and processes, asserting that bureaucracy and corruption, for example, are counterproductive to a participative political life, to economic development and to the recognition of national ethnic minorities. Second, he scrutinizes why federalism might transform this. Here, he assesses various opposing philosophical contentions on federal system in managing ethnically diverse society, like the Philippines, and argue that decentralization of political power, economic and cultural developments are reasons to exit from unitary government. Third, he suggests that federalism can be instrumental to Igorots self-determination. Self-determination is neither opposed to national development nor to the ideals of democracy – liberty, justice, solidarity. For example, as others have already noted, a politics in the vernacular facilitates greater participation among the people. Hence, there is a greater chance to arrive at policies that serve the interest of the people. Some may wary that decentralization disintegrates a nation. According to the author, however, the recognition of minority rights which includes self-determination may promote filial devotion to the state. If Igorot indigenous peoples have access to suitable institutions to determine their political life, economic goals, social needs, i.e., education, culture, language, chances are it moves the country forward to development fostering national unity. Remarkably, federal system thus best responds to the Philippines’s democratic and development deficits. Federalism can also significantly rectify the practices that oppress and dislocate national ethnic minorities as it ensures the creation of localized institutions for optimum political, economic, cultural determination and maximizes representation in the public sphere.

Keywords: federalism, Igorot, indigenous peoples, self-determination

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Authors: Martin Bloomfield

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This paper examines frictions that lie at the heart of any pragmatist conception of religion and moral progress. I take moral progress to require the ability to correctly analyse social problems, provide workable solutions to these problems, and then rationally justify the analyses and solutions used. I take religion here to involve, as a minimal requirement, belief in the existence of God, a god, or gods, such that they are recognisable to most informed observers within the Western tradition. I take pragmatism to belong to, and borrow from, the philosophical traditions of non-absolutism, anti-realism, historicism, and voluntarism. For clarity, the relevant brands of each of these traditions will be examined during the paper. The friction identified in the title may be summed up as follows: those who, like Cornel West (and, when he was alive, Hilary Putnam), are theistic pragmatists with an interest in realising moral progress, have all been aware of a problem inherent in their positions. Assuming it can be argued that religion and moral progress are compatible, a non-absolutist, anti-realist, historicist position nevertheless raises problems that, as Leon Wieseltier pointed out, the pragmatist still believes in a God who isn’t real, and that the truth of any religious statement (including “God exists”) is relative not to any objective reality but to communities of engaged interlocutors; and that, where there are no absolute standards of right and wrong, any analysis of (and solution to) social problems can only be rationally justified relative to one or another community or moral and epistemic framework. Attempts made to universalise these frameworks, notably by Dewey, Gadamer, and Bernstein, through democracy and hermeneutics, fall into either a vicious and infinite regress, or (taking inspiration from Habermas) the problem of moral truths being decided through structures of power. The paper removes this friction by highlighting the work of Christian pragmatist Cornel West through the lens of the philosopher of religion Eleanore Stump. While West recognises that for the pragmatist, the correctness of any propositions about God or moral progress is impossible to rationally justify to any outside the religious, moral or epistemic framework of the speakers themselves without, as he calls it, a ‘locus of truth’ (which is itself free from the difficulties Dewey, Gadamer and Bernstein fall victim to), Stump identifies routes to knowledge which provide such a locus while avoiding the problems of relativism, power dynamics, and regress. She describes “Dominican” and “Franciscan” knowledge (roughly characterised as “propositional” and “non-propositional”), and uses this distinction to identify something Bernstein saw as missing from Gadamer: culture-independent norms, upon which universal agreement can be built. The “Franciscan knowledge” Stump identifies as key is second-personal knowledge of Christ. For West, this allows the knower to access vital culture-independent norms. If correct, instead of the classical view (religion is incompatible with pragmatism), Christianity becomes key to pragmatist knowledge and moral-knowledge claims. Rather than being undermined by pragmatism, Christianity enables pragmatists to make moral and epistemic claims, free from troubling power dynamics and cultural relativism.

Keywords: Cornel West, Cultural Relativism, Gadamer, Philosophy of Religion, Pragmatism

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Authors: Toufic Sarieddine

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The current debate on the hegemonic impact of China’s Belt and Road Initiative (BRI) is of two opposing strands: Resilient and absolute US hegemony on the one hand and various models of multipolar hegemony such as bifurcation on the other. Bifurcation theories illustrate an unprecedented division of hegemonic functions between China and the US, whereby Beijing becomes the world’s economic hegemon, leaving Washington the world’s military hegemon and security guarantor. While consensus points to China being the main driver of unipolarity’s rupturing, the debate among bifurcationists is on the location of the first rupture. In this regard, the Middle East and North Africa (MENA) region has seen increasing Chinese foreign direct investment in recent years while that to other regions has declined, ranking it second in 2018 as part of the financing for the Maritime Silk Road Initiative (MSRI). China has also become the top trade partner of 11 states in the MENA region, as well as its top source of machine imports, surpassing the US and achieving an overall trade surplus almost double that of Washington’s. These are among other features outlined in world-systems analysis (WSA) literature which correspond with the emergence of a new hegemon. WSA is further utilized to gauge other facets of China’s increasing involvement in MENA and assess whether bifurcation is unfolding therein. These features of hegemony include the adoption of China’s modi operandi, economic dominance in production, trade, and finance, military capacity, cultural hegemony in ideology, education, and language, and the promotion of a general interest around which to rally potential peripheries (MENA states in this case). China’s modi operandi has seen some adoption with regards to support against the United Nations Convention on the Law of the Sea, oil bonds denominated in the yuan, and financial institutions such as the Shanghai Gold Exchange enjoying increasing Arab patronage. However, recent elections in Qatar, as well as liberal reforms in Saudi Arabia, demonstrate Washington’s stronger normative influence. Meanwhile, Washington’s economic dominance is challenged by China’s sizable machine exports, increasing overall imports, and widening trade surplus, but retains some clout via dominant arms and transport exports, as well as free-trade deals across the region. Militarily, Washington bests Beijing’s arms exports, has a dominant and well-established presence in the region, and successfully blocked Beijing’s attempt to penetrate through the UAE. Culturally, Beijing enjoys higher favorability in Arab public opinion, and its broadcast networks have found some resonance with Arab audiences. In education, the West remains MENA students’ preferred destination. Further, while Mandarin has become increasingly available in schools across MENA, its usage and availability still lag far behind English. Finally, Beijing’s general interest in infrastructure provision and prioritizing economic development over social justice and democracy provides an avenue for increased incorporation between Beijing and the MENA region. The overall analysis shows solid progress towards bifurcation in MENA.

Keywords: belt and road initiative, hegemony, Middle East and North Africa, world-systems analysis

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Authors: Muhammad Alhada Fuadilah Habib, Ayla Karina Budita, Cut Rizka Al Usrah, Mukhammad Fatkhullah, Kanita Khoirun Nisa, Siti Muslihatul Mukaromah

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In this contemporary era, the term of development often emphasised merely on the economic growth aspect. Development of a program often considered as superior by the government, in fact, it often raises various problems. The problems occur because the development policies determined by the government tend to favor private entrepreneurs and impose on the oppression toward the community. The development promised to prosper the community's life, turn out in fact of harming the community, threatening the survival of the community and damaging the ecosystem of nature where the community hangs their life to it. Nowadays many natural resources should be used for the community’s life prosperity. However, the prosperity is conquered by the private entrepreneurs that are regulated through the free market mechanism and wrapped in democratization. This condition actually is a form of neoliberalism that builds new administration order system which is far from the meaning of the word democracy. The government should play more role in protecting community's life and prosperity, but in fact, the government sides with the private entrepreneurs for the sake of the economic benefits regardless of other aspects of the community’s life. This unjustified condition presents a wide range of social movements from the community in response to the neoliberalis policy that actually eliminates the doctrine of community sovereignty. Social movements performed by Yogyakarta south coastal area community, as the focus of the discussion in this paper, is one of the community’s response toward the government policies related to the construction of the ferruginous sand quarry which is tend to favor on private entrepreneurs and highly prejudicing or even threatening the survival of Yogyakarta south coastal area community. The data collection in this study uses qualitative research methods with in-depth interview data collection techniques and purposive informant determination techniques. This method was chosen in order to obtain the insightful data and detailed information to uncover the injustice policies committed by the government-private entrepreneurs toward Yogyakarta south coastal area community. The brief results of this study show that the conflicts between the community and government-private entrepreneurs occurred because of the differences of interests and paradigm of natural resource management. The resistance movements done by the community to fight back the government-private entrepreneurs was conducted by forming an organization called Paguyupan Petani Lahan Pantai Kulon Progo (PPLP-KP). This organization do the resistances through two ways; firstly, quiet action done through various actions such as; refusing against the socialization, performing discussion to deliberate their argument with the government-private entrepreneurs, complaining the problems to the central government, creating banners or billboards which contain the writing of rejection, performing pray rituals to invoke the justice from the God, as well as instill the resistance ideology to their young generation. Secondly, the rough action also is done through various actions such as; doing roadblocks, conducting rallies, as well as doing clash with the government apparatus. In case the resistances done by the community are seen from the pattern. Actually, the resistances are reaction toward the aggression carried out by the government-private entrepreneurs.

Keywords: community resistance, conflict, ferruginous sand quarry construction, social movement

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Authors: Bruna Azzari Puga, Richard Roe, Andre Pagani de Souza

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abstract outlines a proposed study to examine how and to what extent interactive, experiential, learner centered methodology develops learning of basic civic and democratic competencies among young children. It stems from the Literacy and Law course taught at Georgetown University Law Center in Washington, DC, since 1998. Law students, trained in best literacy practices and legal cases affecting literacy development, read “law related” children’s books and engage in interactive and extension activities with emerging readers. The law students write a monthly journal describing their experiences and a final paper: a conventional paper or a children’s book illuminating some aspect of literacy and law. This proposal is based on the recent adaptation of Literacy and Law to Brazil at Mackenzie Presbyterian University in São Paulo in three forms: first, a course similar to the US model, often conducted jointly online with Brazilian and US law students; second, a similar course that combines readings of children’s literature with activity based learning, with law students from a satellite Mackenzie campus, for young children from a vulnerable community near the city; and third, a course taught by law students at the main Mackenzie campus for 4th grade students at the Mackenzie elementary school, that is wholly activity and discourse based. The workings and outcomes of these courses are well documented by photographs, reports, lesson plans, and law student journals. The authors, faculty who teach the above courses at Mackenzie and Georgetown, observe that literacy, broadly defined as cognitive and expressive development through reading and discourse-based activities, can be influential in developing democratic civic skills, identifiable by explicit civic competencies. For example, children experience justice in the classroom through cooperation, creativity, diversity, fairness, systemic thinking, and appreciation for rules and their purposes. Moreover, the learning of civic skills as well as the literacy skills is enhanced through interactive, learner centered practices in which the learners experience literacy and civic development. This study will develop rubrics for individual and classroom teaching and supervision by examining 1) the children’s books and students diaries of participating law students and 2) the collection of photos and videos of classroom activities, and 3) faculty and supervisor observations and reports. These rubrics, and the lesson plans and activities which are employed to advance the higher levels of performance outcomes, will be useful in training and supervision and in further replication and promotion of this form of teaching and learning. Examples of outcomes include helping, cooperating and participating; appreciation of viewpoint diversity; knowledge and utilization of democratic processes, including due process, advocacy, individual and shared decision making, consensus building, and voting; establishing and valuing appropriate rules and a reasoned approach to conflict resolution. In conclusion, further development and replication of the learner centered literacy and law practices outlined here can lead to improved qualities of democratic teaching and learning supporting mutual respect, positivity, deep learning, and the common good – foundation qualities of a sustainable world.

Keywords: democracy, law, learner-centered, literacy

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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