Primary Myelofibrosis (PMF)Phase 3MANIFEST-3NCT07357727
A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
A Phase 3 study testing Pelabresib and Ruxolitinib in people with Primary Myelofibrosis (PMF) and Post-polycythemia Vera Myelofibrosis (PPV-MF), run by Novartis Pharmaceuticals at 145 sites in 22 countries.
Trial summary
The purpose of this trial is to evaluate whether treatment with pelabresib in combination with ruxolitinib leads to improved clinical outcomes compared to ruxolitinib alone in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF), Post-essential Thrombocythemia Myelofibrosis (PET-MF)
- What is being tested?
- Pelabresib and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 460 participants
- Where
- 145 sitesin 22 countries
- Study dates
- 27 May 2026to 27 Dec 2030
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants have diagnosis of primary myelofibrosis (PMF) or post-polycythemia vera myelofibrosis (post-PV MF) or post-essential thrombocythemia myelofibrosis (post-ET MF) according to the International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemias 2022
- DIPSS risk category of intermediate-1, intermediate-2 or high-risk
- Spleen volume ≥ 450 cm3 by CT or MRI scan (local read sufficient if no central read available)
- Have an average TSS of ≥15 within 7 days prior to randomization, using MFSAF v. 4.0 (at least 4 out of 7 TSS assessments required for average calculation)
- Participants with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Blasts <5% in peripheral blood. Assessment of blasts in peripheral blood is mandatory at screening
- Platelet count ≥ 100 x 10^9/L in the absence of growth factors or transfusions for the previous 4 weeks
Who cannot join
- Prior splenectomy at any time or splenic irradiation in the previous 6 months
- Prior hematopoietic cell transplant or participant anticipated to receive a hematopoietic cell transplant within 24 weeks from the date of randomization
- Blasts ≥ 5% in bone marrow if results available at screening or history of accelerated phase (AP) or leukemic transformation
- History of a malignancy (other than MF, PPV-MF or PET-MF) in the past 3 years in need of systemic treatment
- Received any approved or investigational agent other than hydroxyurea or anagrelide for the treatment of MF within 14 days of first dose of study treatment or within 5 half-lives of the approved or investigational agent, whichever is longer
- Prior treatment with any JAK inhibitor or Bromodomain and extraterminal domain (BET) inhibitor
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
145 sites in 22 countries. Contact the study team or a site near you to ask about taking part.
145 sites in 22 countries
United States20 sites, 20 recruiting
- Recruiting
New York Oncology Hematology P C
Albany, New York, 12206
Rachel Page, rachel.page@nyoh.com
Lawrence Garbo
- Recruiting
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Danielle Alexander, danielle.oliver@emory.edu
Anthony Michael Hunter
- Recruiting
Texas Oncology - Central South
Austin, Texas, 78705
Marian Heaven, marian.heaven@usoncology.com
Jason M Melear
- Recruiting
Summit Medical Group Oncology
Berkeley Heights, New Jersey, 07922
Michelle Mackenzie, 973-436-1755, mmackenzie@summithealth.com
Dipen Patel
- Recruiting
American Oncology Partners PA Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
Raissa Toure, raissa.toure@aoncology.com
Ralph Boccia
- Recruiting
University of Chicago Hospital
Chicago, Illinois, 60637
Ellen Malone, ellen.malone@northwestern.edu
Anand Patel
- Recruiting
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43221
Hannah Davis, Hannah.Davis@osumc.edu
Andrew Srisuwananukorn
- Recruiting
Texas Oncology PA Dallas Presbyterian Hospital
Dallas, Texas, 75231
Jessica Maner, 214-265-2080, Jessica.Maner@usoncology.com
Khoan Vu
- Recruiting
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Kelly Beland, 303-418-7600, Kelly.beland@usoncology.com
Christopher Benton
- Recruiting
Florida Cancer Specialist South Reg
Fort Myers, Florida, 33916
Christina Caruso, Ccaruso@flcancer.com
Fadi Kayali
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Maria Pinsoy, mbpinsoy@mdanderson.org
Prithviraj Bose
- Recruiting
Franciscan Health Indianapolis
Indianapolis, Indiana, 42637
Melanie Coleman, melanie.coleman@franciscanalliance.org
Waled Bahaj
- Recruiting
The Anderson Family Cancer Institute
Jupiter, Florida, 33458
Christine Leonard, christine.leonard@jupitermed.com
Ryan Devine
- Recruiting
Miami NS Ins Baptist Health S FL
Miami, Florida, 33176
Dixie Carmona Gonzalez, 786-596-2000, Dixie.CarmonaGonzalez@baptisthealth.net
Firas El Chaer
- Recruiting
Yale University School Of Medicine
New Haven, Connecticut, 06520
Farah Fasihuddin, farah.fasihuddin@yale.edu
Nikolai Podoltsev
- Recruiting
Columbia University Medical Center New York Presbyterian
New York, New York, 10032
Nicole Conwell, 212-305-6953, nc3272@cumc.columbia.edu
Monica Kasbekar
- Recruiting
Fred Hutch Cancer Research
Seattle, Washington, 98109
Lisa Grimm, lgrimm@fredhutch.org
Bart Scott
- Recruiting
Florida Cancer Specialists-North
St. Petersburg, Florida, 33705
Kelly Whitehead, kelly.whitehead@flcancer.com
Viralkumar Bhanderi
- Recruiting
Florida Cancer Specialists East
Stuart, Florida, 34994
Mary Jo Luser, MaryJo.Luser@flcancer.com
Judah Friedman
- Recruiting
SCRI Texas Oncology Northeast Texas
Tyler, Texas, 75702
Shelly Maxfield, shelly.maxfield@usoncology.com
Shail Dalal
China20 sites, 20 recruiting
- Recruiting
Novartis Investigative Site
Beijing, 100730
- Recruiting
Novartis Investigative Site
Changchun, Jilin, 130021
- Recruiting
Novartis Investigative Site
Chongqing, 400016
- Recruiting
Novartis Investigative Site
Fuzhou, 350001
- Recruiting
Novartis Investigative Site
Guangzhou, Guangdong, 510080
- Recruiting
Novartis Investigative Site
Guangzhou, Guangdong, 510515
- Recruiting
Novartis Investigative Site
Hangzhou, Zhejiang, 310003
- Recruiting
Novartis Investigative Site
Hefei, Anhui, 230001
- Recruiting
Novartis Investigative Site
Jinan, Shandong, 250012
- Recruiting
Novartis Investigative Site
Kunming, Yunnan, 650101
- Recruiting
Novartis Investigative Site
Nanchang, Jiangxi, 330006
- Recruiting
Novartis Investigative Site
Nanjing, Jiangsu, 210029
- Recruiting
Novartis Investigative Site
Nantong, Jiangsu, 226000
- Recruiting
Novartis Investigative Site
Shanghai, 200025
- Recruiting
Novartis Investigative Site
Shenyang, 110004
- Recruiting
Novartis Investigative Site
Tianjin, 300020
- Recruiting
Novartis Investigative Site
Wenzhou, Zhejiang, 325000
- Recruiting
Novartis Investigative Site
Wuhan, Hubei, 430022
- Recruiting
Novartis Investigative Site
Wuhan, Hubei, 430030
- Recruiting
Novartis Investigative Site
Yantai, Shandong, 264000
Japan12 sites, 12 recruiting
- Recruiting
Novartis Investigative Site
Bunkyo Ku, Tokyo, 1138431
- Recruiting
Novartis Investigative Site
Bunkyo-ku, Tokyo, 1138603
- Recruiting
Novartis Investigative Site
Chūō, Yamanashi, 4093898
- Recruiting
Novartis Investigative Site
Fukuoka, 8128582
- Recruiting
Novartis Investigative Site
Kamogawa, Chiba, 2968602
- Recruiting
Novartis Investigative Site
Kobe, Hyōgo, 6500047
- Recruiting
Novartis Investigative Site
Kumamoto, 8628655
- Recruiting
Novartis Investigative Site
Kurashiki, Okayama-ken, 7108602
- Recruiting
Novartis Investigative Site
Miyazaki, 8891692
- Recruiting
Novartis Investigative Site
Sapporo, Hokkaido, 0030006
- Recruiting
Novartis Investigative Site
Shiwa-Gun, Iwate, 0283695
- Recruiting
Novartis Investigative Site
Tsu, Mie-ken, 5148507
France9 sites, 9 recruiting
- Recruiting
Novartis Investigative Site
Brest, 29200
- Recruiting
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275
- Recruiting
Novartis Investigative Site
Lens, 62307
- Recruiting
Novartis Investigative Site
Nîmes, 30029
- Recruiting
Novartis Investigative Site
Paris, 75475
- Recruiting
Novartis Investigative Site
Pessac, 33604
- Recruiting
Novartis Investigative Site
Poitiers, 86021
- Recruiting
Novartis Investigative Site
Rennes, 35033
- Recruiting
Novartis Investigative Site
Toulouse, 31059
Spain9 sites, 9 recruiting
- Recruiting
Novartis Investigative Site
Alicante, 03010
- Recruiting
Novartis Investigative Site
Barcelona, 08035
- Recruiting
Novartis Investigative Site
Donostia / San Sebastian, Gipuzkoa, 20014
- Recruiting
Novartis Investigative Site
El Palmar, Murcia, 30120
- Recruiting
Novartis Investigative Site
Las Palmas GC, 35010
- Recruiting
Novartis Investigative Site
Madrid, 28009
- Recruiting
Novartis Investigative Site
Málaga, 29010
- Recruiting
Novartis Investigative Site
Pamplona, Navarre, 31008
- Recruiting
Novartis Investigative Site
Salamanca, 37007
Turkey (Türkiye)9 sites, 9 recruiting
- Recruiting
Novartis Investigative Site
Ankara, Kecioren, 06010
- Recruiting
Novartis Investigative Site
Ankara, Sihhiye Altindag, 06230
- Recruiting
Novartis Investigative Site
Ankara, 06000
- Recruiting
Novartis Investigative Site
Istanbul, Fatih, 34098
- Recruiting
Novartis Investigative Site
Istanbul, Pendik, 34899
- Recruiting
Novartis Investigative Site
Izmir, 35060
- Recruiting
Novartis Investigative Site
Kocaeli, 41380
- Recruiting
Novartis Investigative Site
Sakarya, Adapazari, 54290
- Recruiting
Novartis Investigative Site
Samsun, 55200
South Korea8 sites, 8 recruiting
- Recruiting
Novartis Investigative Site
Busan, 49241
- Recruiting
Novartis Investigative Site
Jeonju, Jeollabuk-do, 54907
- Recruiting
Novartis Investigative Site
Seoul, Yangcheon Gu, 07985
- Recruiting
Novartis Investigative Site
Seoul, 03080
- Recruiting
Novartis Investigative Site
Seoul, 05505
- Recruiting
Novartis Investigative Site
Seoul, 06351
- Recruiting
Novartis Investigative Site
Seoul, 06591
- Recruiting
Novartis Investigative Site
Suwon, Gyeonggi-do, 16247
Italy7 sites, 7 recruiting
- Recruiting
Novartis Investigative Site
Florence, FI, 50134
- Recruiting
Novartis Investigative Site
Meldola, FC, 47014
- Recruiting
Novartis Investigative Site
Monza, MB, 20900
- Recruiting
Novartis Investigative Site
Novara, 28100
- Recruiting
Novartis Investigative Site
Padova, PD, 35128
- Recruiting
Novartis Investigative Site
Roma, RM, 00161
- Recruiting
Novartis Investigative Site
Verona, VR, 37134
Poland7 sites, 7 recruiting
- Recruiting
Novartis Investigative Site
Gdansk, 80-214
- Recruiting
Novartis Investigative Site
Katowice, 40-519
- Recruiting
Novartis Investigative Site
Lublin, 20-090
- Recruiting
Novartis Investigative Site
Skorzewo, 60-185
- Recruiting
Novartis Investigative Site
Torun, 87-100
- Recruiting
Novartis Investigative Site
Wałbrzych, 58-309
- Recruiting
Novartis Investigative Site
Warsaw, 02-776
Germany5 sites, 5 recruiting
- Recruiting
Novartis Investigative Site
Aachen, 52074
- Recruiting
Novartis Investigative Site
Cottbus, 03046
- Recruiting
Novartis Investigative Site
Erlangen, 91054
- Recruiting
Novartis Investigative Site
Hamburg, 20246
- Recruiting
Novartis Investigative Site
Mannheim, Baden-Wurttemberg, 68305
India5 sites, 5 recruiting
- Recruiting
Novartis Investigative Site
Aurangabad, Maharashtra, 431005
- Recruiting
Novartis Investigative Site
Delhi, 110085
- Recruiting
Novartis Investigative Site
Kolkata, West Bengal, 700014
- Recruiting
Novartis Investigative Site
Pune, Maharashtra, 411006
- Recruiting
Novartis Investigative Site
Rishikesh, Uttarakhand, 249203
Malaysia5 sites, 5 recruiting
- Recruiting
Novartis Investigative Site
George Town, Pulau Pinang, 10450
- Recruiting
Novartis Investigative Site
Johor Bahru, 80100
- Recruiting
Novartis Investigative Site
Kota Kinabalu, Sabah, 88586
- Recruiting
Novartis Investigative Site
Kuala Selangor, 68000
- Recruiting
Novartis Investigative Site
Kuching, Sarawak, 93586
Argentina4 sites, 4 recruiting
- Recruiting
Hospital de Clinicas Jose de San Martin
Buenos Aires, Buenos Aires F.D., 1221
+54911 49910959, francarojas@gmail.com
Francisca Rojas
- Recruiting
Hospital Italiano de Buenos Aires
CABA, C1181ACH
+54911 6937 0731, georgina.bendek@hospitalitaliano.org.ar
Georgina Bendek
- Recruiting
FUNDALEU
Capital Federal, C1114AAN
+54 9 11 4972 0765, fsackmann@fundaleu.org.ar
Federico Sackmann, Dr
- Recruiting
Hospital Privado de Cordoba
Córdoba, X5016KEH
+54 9 1569634187, ana.basquiera@hospitalprivado.com.ar
Ana Lisa Basquiera
Brazil4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Barretos, São Paulo, 14784-400
- Recruiting
Novartis Investigative Site
Curitiba, Paraná, 80060-240
- Recruiting
Grupo ELORA
Florianópolis, Santa Catarina, 88020-210
Camila Sommer, +55 48 99105-7542, camila.sommer@grupoelora.org.br
Jaisson Bortolini
- Recruiting
Novartis Investigative Site
Goiânia, Goiás, 74605-050
Czechia4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Brno, 625 00
- Recruiting
Novartis Investigative Site
Hradec Králové, 500 05
- Recruiting
Novartis Investigative Site
Olomouc, 779 00
- Recruiting
Novartis Investigative Site
Ostrava, Poruba, 708 52
Switzerland4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Basel, 4058
- Recruiting
Novartis Investigative Site
Bern, 3010
- Recruiting
Novartis Investigative Site
Geneva, 1211
- Recruiting
Novartis Investigative Site
Genolier, 1272
Taiwan4 sites, 4 recruiting
- Recruiting
Novartis Investigative Site
Changhua, 50006
- Recruiting
Novartis Investigative Site
Kaohsiung City, 80756
- Recruiting
Novartis Investigative Site
Tainan, 704302
- Recruiting
Novartis Investigative Site
Taipei, 10002
Austria3 sites, 3 recruiting
- Recruiting
Novartis Investigative Site
Graz, 8036
- Recruiting
Novartis Investigative Site
Sankt Pölten, 3100
- Recruiting
Novartis Investigative Site
Vienna, 1140
Australia2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Adelaide, South Australia, 5000
- Recruiting
Novartis Investigative Site
Clayton, Victoria, 3168
Netherlands2 sites, 2 recruiting
- Recruiting
Novartis Investigative Site
Amsterdam, North Holland, 1081 HV
- Recruiting
Novartis Investigative Site
Utrecht, 3584 CX
Belgium1 site, 1 recruiting
- Recruiting
Novartis Investigative Site
Woluwe-Saint-Lambert, Brussels Capital, 1200
Canada1 site, 1 recruiting
- Recruiting
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Shireen Sirhan, Dr, 514-340-8222 ext. 24572, shireen.sirhan@mail.mcgill.ca
Shireen Sirhan
About this study
Official title: A Phase 3, Randomized, Double-blind, Active-control Study of Pelabresib (DAK539) and Ruxolitinib vs. Placebo and Ruxolitinib in Adult Patients With Myelofibrosis Who Are JAK Inhibitor Naive
The purpose of this trial is to evaluate whether treatment with pelabresib in combination with ruxolitinib leads to improved clinical outcomes compared to ruxolitinib alone in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), or post-essential thrombocythemia myelofibrosis (PET-MF) who have not previously received Janus kinase (JAK) inhibitor therapy.
Read the detailed description
The study for each participant is composed of several distinct periods: a screening period, a study treatment period, and a post-treatment follow-up phase.
- Screening Period: The screening period lasts for up to 28 days prior to Cycle 1 Day 1, which marks the beginning of treatment. During this time, the participant's eligibility for the study is confirmed, informed consent is obtained, and all required baseline assessments are completed.
- Treatment Period: The treatment period begins on Cycle 1 Day 1, which is the point of randomization and the start of study treatment. This period continues until the participant permanently discontinues study treatment, which may occur due to disease progression, unacceptable toxicity, participant withdrawal, or other reasons specified in the protocol. Throughout this period, participants receive study drugs in 21-day cycles, with pelabresib or placebo administered for 14 days and ruxolitinib given continuously. Regular site visits and assessments are conducted according to the Schedule of Activities.
- Safety Follow-up Period: The safety follow-up period extends for 30 days (with a window of plus or minus 3 days) after the participant receives their last dose of pelabresib or placebo. During this period, participants are monitored for any late-onset adverse events or safety concerns that may arise after discontinuing the study treatment.
- Efficacy Follow-up Period: Following the safety follow-up, efficacy follow-up visits are scheduled every 12 weeks for participants who have not shown evidence of disease progression, meaning there is no documented progression of splenomegaly or leukemic transformation and no new therapy for myelofibrosis has been started. The purpose of this follow-up is to continue monitoring efficacy endpoints, such as spleen imaging, laboratory assessments, and bone marrow biopsies, until either disease progression occurs or a new therapy is initiated.
- Survival Follow-up Period:
Once a participant enters the survival follow-up phase, follow-up visits are conducted every 12 weeks and may be performed remotely. This phase applies to participants who have experienced documented disease progression or have started a new therapy for myelofibrosis. The aim of survival follow-up is to monitor overall survival and to collect ongoing data regarding disease status and any subsequent therapies the participant may receive.
- Conditions
- Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF), Post-essential Thrombocythemia Myelofibrosis (PET-MF)
- Being tested
- Pelabresib, Ruxolitinib, Placebo
- Keywords
- Pelabresib (DAK539), Ruxolitinib, Adult participants, Myelofibrosis (MF)
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PelabresibDrug
Also called DAK539
Pelabresib monohydrate tablets
RuxolitinibDrug
Also called INC424
Ruxolitinib phosphate tablets
PlaceboDrug
Matches pelabresib
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Pelabresib + Ruxolitinib | Experimental | Participants in this arm receive pelabresib (DAK539) orally once daily for 14 days of each 21-day cycle, in combination with ruxolitinib, which is taken orally twice daily throughout each cycle. Participants may continue receiving study treatment until they experience unacceptable toxicity, disease progression, or until either the investigator or the participant decides to discontinue treatment. Receives: Drug: Pelabresib; Drug: Ruxolitinib |
| Arm 2: Placebo + Ruxolitinib | Placebo comparator | Participants in this arm receive a matching placebo orally once daily for 14 days of each 21-day cycle, together with ruxolitinib, which is also taken orally twice daily throughout each cycle.
Participants may continue receiving study treatment until they experience unacceptable toxicity, disease progression, or until either the investigator or the participant decides to discontinue treatment. Receives: Drug: Ruxolitinib; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline total symptom score (TSS) ≥ 25
Spleen Response (SVR35) is defined as achieving a reduction of at least 35 percent in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and assessed by a centralized radiology review in participants with baseline TSS ≥ 25.
Measured: Week 24
Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS ≥ 25
Symptom improvement at Week 24 is defined as the absolute change from baseline in the total symptom score (TSS) at Week 24, as measured by the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) in participants with baseline TSS ≥ 25.
Measured: Baseline, Week 24
Number of Participants with Splenic Response (SVR35) by Central Radiology Reads at Week 24 in participants with baseline TSS ≥ 15
Spleen Response (SVR35) is defined as achieving a reduction of at least 35 percent in spleen volume from baseline to Week 24, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and assessed by a centralized radiology review in participants with baseline TSS ≥ 15.
Measured: Week 24
Absolute change from baseline in total symptom score (TSS) at Week 24 in participants with baseline TSS ≥ 15
Symptom improvement at Week 24 is defined as the absolute change from baseline in the total symptom score (TSS) at Week 24, as measured by the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) in participants with baseline TSS ≥ 15.
Measured: Baseline, Week 24
Secondary outcomes (24)
Number of Participants with Splenic Response (SVR35) by Central Radiology Reads over time
Spleen Response (SVR35) over time is defined as achieving a reduction of at least 35 percent in spleen volume from baseline to Week 12, Week 36, Week 48 and thereafter, as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and assessed by a centralized radiology review.
Measured: Week 12, Week 36, Week 48 and every 12 weeks thereafter till End of Study (an average of 3 years)
Absolute change from baseline and percentage change from baseline in spleen volume over time
Absolute and percentage change from baseline in spleen volume over time will be summarized using descriptive summary statistics
Measured: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)
Time to first SVR35 response
Time to first SVR35 response defined as the time from date of randomization to the date of first SVR35 response as measured by MRI (or CT scan) will be summarized by treatment arm.
Measured: From date of randomization to the date of first SVR35 response, assessed up to approximately 3 years
Duration of first SVR35 response
Duration of first SVR35 response defined as the time from first SVR35 response to loss of response for any participant who reaches SVR35 at any time.
Measured: From first SVR35 response to loss of response, assessed up to approximately 3 years
Number of Participants with TSS50 response at Week 24
Symptom response defined as achieving ≥ 50% reduction in total symptom score (TSS50) from baseline to Week 24 as measured by the MFSAF v4.0
Measured: Week 24
Number of Participants with TSS50 response over time
Symptom response defined as achieving ≥ 50% reduction in total symptom score (TSS50) from baseline to Week 12, Week 36, Week 48 and thereafter as measured by the MFSAF v4.0
Measured: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)
Absolute and percentage change from baseline in TSS over time
Absolute change from baseline and percentage change from baseline in TSS over time
Measured: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)
Time to first TSS50 response
Time to first TSS50 response defined as the time from date of randomization to the date of first TSS50 response as measured by the MFSAF v4.0.
Measured: From date of randomization till date of first TSS50 response, assessed up to approximately 3 years
Duration of TSS50 response
Duration of TSS50 response defined as the time from first TSS50 response to loss of response for any participant who reaches TSS50 at any time.
Measured: From first TSS50 response to loss of response, assessed up to approximately 3 years
Dual Response (SVR35 + TSS50)
Dual response is defined as achieving both ≥ 35% reduction in spleen volume (SVR35) and ≥ 50% reduction in total symptom score (TSS50) from baseline to Week 12, 24, 36, 48 and every 12 weeks thereafter, with SVR measured by MRI (or CT scan) and assessed by central radiology read and TSS measured by MFSAF v4.0.
Measured: Baseline, Week 12, Week 24, Week 36, Week 48, and every 12 weeks thereafter till End of Study (an average of 3 years)
Hemoglobin response
Hemoglobin response defined as a ≥1.5 g/dL average increase in hemoglobin from baseline in any 12-week mean hemoglobin concentration.
Measured: 12 consecutive weeks (rolling window) up to 7 days following last dose of pelabresib/placebo
Change from baseline in hemoglobin over time
Change from baseline in hemoglobin over time will be summarized using descriptive summary statistics.
Measured: Up to 7 days following last dose of pelabresib/placebo
Anemia response over time
Anemia response (major response, minor response, stable anemia, progressive anemia) as per proposed 2024 IWG-ELN criteria in participants with transfusion dependent and non-transfusion dependent anemia (Tefferi et al 2024).
Measured: Up to 7 days following last dose of pelabresib/placebo
Overall survival (OS)
Overall survival (OS) defined as the time from date of randomization to date of death due to any cause.
Measured: From date of randomization till date of death due to any cause, assessed up to approximately 3 years
Progression-free survival (PFS)
Progression-free survival (PFS) defined as the time from date of randomization to date of documented disease progression, or death due to any cause whichever comes first.
Measured: From date of randomization till date of documented disease progression, or death due to any cause whichever comes first, assessed up to approximately 3 years
Leukemia-free survival (LFS)
Leukemia-free survival (LFS) is defined as the time from date of randomization to date of leukemic transformation, or death due to any cause whichever comes first.
Measured: From date of randomization till date of leukemic transformation, or death due to any cause whichever comes first, assessed up to approximately 3 years
Exposure-Adjusted Incidence Rate (EAIR) of Participants with Leukemic Transformation
The EAIR of participants with leukemic transformation is the rate at which this event occurs, adjusted for the actual time participants were exposed to the study drug(s).
Measured: Throughout study completion (an average of 3 years)
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of adverse events by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Measured: Up to 30 days following last dose of pelabresib/placebo
Pelabresib plasma concentrations
Blood samples for pelabresib pharmacokinetics (PK) will be obtained and evaluated in all participants at all dose levels and summarized using descriptive statistics.
Measured: Cycle 1: Day 1 (0/Pre-dose and 0.5 post dose), Day 7 (0/Pre-dose), Day 14 (0/Pre-dose, 2, and 5 hours post-dose). 1 cycle = 21 days.
Maximum observed plasma Concentration (Cmax) of pelabresib in participants enrolled in China and Japan
Venous whole blood samples will be collected for pharmacokinetic characterization in a subset of participants enrolled in China and Japan. Cmax will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Day Day 14 (0/Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose). 1 cycle = 21 days.
Time to Maximum observed plasma Concentration (Tmax) of pelabresib in participants enrolled in China and Japan
Venous whole blood samples will be collected for pharmacokinetic characterization in a subset of participants enrolled in China and Japan. Tmax will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Day Day 14 (0/Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose). 1 cycle = 21 days.
Area Under the Concentration-Time Curve over a dosing interval (AUCtau) of pelabresib in participants enrolled in China and Japan
Venous whole blood samples will be collected for pharmacokinetic characterization in a subset of participants enrolled in China and Japan. AUCtau will be listed and summarized using descriptive statistics.
Measured: Cycle 1 Day Day 14 (0/Pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose). 1 cycle = 21 days.
Change from baseline over time in fatigue as measured by PROMIS SF v1.0 Fatigue 7a
The PROMIS Short Form version 1.0 Fatigue 7a is a seven-question survey that measures how much fatigue has affected a person over the past week. Each question is rated from "Never" to "Always" on a five-point scale. The total score is converted to a standardized score, where the average is 50 and the standard deviation is 10.
A lower score means less fatigue and minimal impact on daily life, while a higher score indicates more severe fatigue and greater disruption of daily activities.
Measured: Baseline, once per week from Cycles 1 to 9 (each cycle is 21 days), day 1 of every odd cycle thereafter, within 7 days of last dose of pelabresib/placebo and at 12 weeks following last dose of pelabresib/placebo
Change from baseline over time in overall QOL and functional scales as measured by the EORTC QLQ-C30
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) measures overall quality of life and key functional areas in people with cancer, including physical, role, emotional, cognitive, and social functioning.
Items are rated from 1 (not at all) to 4 (very much), except for the global quality of life scale, which uses a 1 to 7 scale.
Scores are converted to a 0 to 100 scale.
Higher scores indicate better functioning and quality of life, while lower scores reflect poorer functioning and well-being.
Measured: Baseline, day 1 of every cycle from Cycle 1 to 9 (each cycle is 21 days), day 1 of every odd cycle thereafter, within 7 days of last dose of pelabresib/placebo and at 12 weeks following last dose of pelabresib/placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2026
- Study start27 May 2026
- Primary completion17 May 2028 (estimated)
- Study completion27 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Myelofibrosis (PMF)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 460 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07357727
- Sponsor's protocol ID
- CDAK539A12303
- Other IDs
- 2025-523555-66-00, 2025
- Acronym
- MANIFEST-3
- Status last verified
- Oct 2026
- First submitted
- 15 Jan 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com