NCT03952039 (FREEDOM2) is a Phase 3 clinical trial of FEDRATINIB in Primary Myelofibrosis, sponsored by Celgene.

Who is sponsoring NCT03952039?

NCT03952039 is sponsored by Celgene.

What drugs are being tested in NCT03952039?

Interventions in NCT03952039: FEDRATINIB, Best Available Therapy (BAT).

What condition does NCT03952039 study?

NCT03952039 studies Primary Myelofibrosis, Post-Polycythemia Vera, Myelofibrosis.

Is NCT03952039 still recruiting?

NCT03952039 is currently completed. Last updated 28 August 2025.

Are results published for NCT03952039?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2025-08-28 · How we verify

NCT03952039: FREEDOM2

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib

Completed Phase 3 Results posted Last updated 28 August 2025

What this trial tests

Phase 3 trial testing FEDRATINIB in Primary Myelofibrosis in 202 participants. Completed in 28 July 2025.

Timeline

9 September 2019

Primary endpoint
15 December 2022

28 July 2025

Quick facts

Lead sponsor	Celgene
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	202
Start date	9 September 2019
Primary completion	15 December 2022
Estimated completion	28 July 2025
Sites	107 locations across France, Italy, Netherlands, Russia, Belgium, Austria, Ireland, United Kingdom

Drugs / interventions tested

FEDRATINIB (FEDRATINIB) — full drug profile →
Best Available Therapy (BAT) — full drug profile →

Conditions studied

Primary Myelofibrosis — all drugs for Primary Myelofibrosis →
Post-Polycythemia Vera — all drugs for Post-Polycythemia Vera →
Myelofibrosis — all drugs for Myelofibrosis →

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Primary Myelofibrosis or Post-Polycythemia Vera. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Spleen Volume Response Rate (RR) Primary · From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days

Percentage of participants who have ≥ 35% spleen volume reduction (SVR) at end of cycle 6 A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.

Group	Value	95% CI
Fedratinib	35.8	27.7 – 44.6
Best Available Therapy (BAT)	6.0	1.7 – 14.6

Symptom Response Rate (SRR) Secondary · From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

Percentage of participants with ≥ 50% reduction in total symptom scores measured by Myelofibrosis Symptom Assessment Form (MFSAF) 4.0 at end of cycle 6. Subjects with a missing TSS at the end of cycle 6 or who had disease progression before the end of the cycle 6 will be considered non-responders. MFSAF measures the sum of 7 symptoms on a scale from 0 to 10 (0 being absent and 10 being the worst imagineable). The lower the score the better. A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or

Group	Value	95% CI
Fedratinib	34.1	25.9 – 43.1
Best Available Therapy (BAT)	16.9	8.8 – 28.3

Spleen Volume Response Rate (RR25) Secondary · From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days

Percentage of participants who have ≥ 25% spleen volume reduction (SVR) at end of cycle 6 A Cochran-Mantel-Haenszel (CMH) test to adjust for planned stratification factors (spleen size by palpation, platelet counts and refractory/relapsed or intolerance to ruxolitinib treatment). The RRs and 95% confidence intervals (CI) will be provided for each arm as well as for the difference in RRs and 95% confidence interval of the difference for fedratinib to BAT.

Group	Value	95% CI
Fedratinib	47.0	38.3 – 55.8
Best Available Therapy (BAT)	13.4	6.3 – 24.0

Number of Participants With All Grade Treatment Emergent Adverse Events (AEs) and Grade 3 to 4 Treatment Emergent AEs Secondary · From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

Number of participants with all grade adverse events (AEs) and grade 3 to 4 AEs

All Grade AEs

Group	Value	95% CI
Fedratinib	132
Best Available Therapy (BAT)	65

Grade 3 and 4 AEs

Group	Value	95% CI
Fedratinib	88
Best Available Therapy (BAT)	29

Number of Participants With Hematology Laboratory Abnormalities Secondary · From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

Number of participants with hematology laboratory abnormalities in the following parameters: hemoglobin (decreased), leukocytes (increase and decrease), lymphocytes (decreased), neutrophils (segmented and band form decreased), Platelets (decreased).

Hemoglobin Decreased All Grades

Group	Value	95% CI
Fedratinib	129
Best Available Therapy (BAT)	64

Hemoglobin Decreased Grade 3

Group	Value	95% CI
Fedratinib	62
Best Available Therapy (BAT)	20

Hemoglobin Decreased Grade 4

Group	Value	95% CI
Fedratinib	0
Best Available Therapy (BAT)	0

Leukocytes Decreased All Grades

Group	Value	95% CI
Fedratinib	41
Best Available Therapy (BAT)	19

Leukocytes Decreased Grade 3

Group	Value	95% CI
Fedratinib	8
Best Available Therapy (BAT)	3

Leukocytes Decreased Grade 4

Group	Value	95% CI
Fedratinib	1
Best Available Therapy (BAT)	0

Leukocytes Increased All Grades

Group	Value	95% CI
Fedratinib	4
Best Available Therapy (BAT)	4

Leukocytes Increased Grade 3

Group	Value	95% CI
Fedratinib	4
Best Available Therapy (BAT)	4

Spleen Response Rate by Palpation (RRP) Secondary · From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

Spleen response rate by palpation is the percentage of participants at the end of cycle 6 with a spleen response according to the IWG-MRT 2013 criteria. A baseline splenomegaly that is palpable at 5-10 cm, below the LCM, becomes not palpable\*\* or A baseline splenomegaly that is palpable at \> 10 cm, below the LCM, decreases by ≥ 50%\*\* Participants with a missing spleen size assessment at the end of cycle 6 including those who meet the criteria for progression of splenomegaly before end of cycle 6 will be considered not to be responders.

Group	Value	95% CI
Fedratinib	28.4	20.9 – 36.8
Best Available Therapy (BAT)	7.7	2.5 – 17.0

Durability of Spleen Volume Response (DR) Secondary · From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.

Durability of spleen volume response (DR) by MRI/CT is defined as the date from the first documented spleen response (ie, ≥ 35% reduction in spleen volume) to the date of subsequent progressive disease (PD) in spleen volume per the IWG-MRT 2013 criteria or death, whichever is earlier. In the absence of an event before the analysis is performed, the DR will be censored at the date of the last valid assessment performed before the analysis performed date.

Group	Value	95% CI
Fedratinib	86.3	63.0 – 126.4
Best Available Therapy (BAT)	NA	NA – NA

Durability of Spleen Response by Palpation (DRP) Secondary · From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.

Durability of spleen response by palpation (DRP) is defined as time from the date of the first documented palpable spleen response, according to the IWG-MRT 2013 to the date of the subsequent PD in spleen size according to the IWG-MRT 2013 or death, whichever is earlier. Durability of spleen response by palpation according to the IWG-MRT 2013 criteria will be calculated for subjects that have an enlarged spleen at baseline (≥ 5 cm below LCM), and that have a spleen response by palpation. In the absence of an event before the analysis is performed, the DRP will be censored at the date of the la

Group	Value	95% CI
Fedratinib	118.3	76.0 – NA
Best Available Therapy (BAT)	47.1	21.7 – NA

Durability of Symptoms Response (DSR) Secondary · From baseline to end of treatment visit, Approximately on average 53 weeks up to 151 weeks.

The DSR is defined as time from the first documented response in TSS (ie, reduction in TSS ≥ 50%) measured by MFSAF version 4.0 to the first documented TSS reduction \< 50%. In the absence of TSS reduction \< 50% before the analysis performed, the DSR will be censored at the date of the last valid assessment performed before the analysis performed date.

Group	Value	95% CI
Fedratinib	12.1	8.1 – 16.1
Best Available Therapy (BAT)	10.1	4.1 – 16.7

Assessment of the Effectiveness of Risk Mitigation Strategy for ≥3 Grade Gastrointestinal Adverse Events and Any Grade Wernickes Encephalopathy Secondary · From Screening to end of Cycle 6 (1 cycle = 28 days), approximately 196 days

Number of participants with a CTCAE Grade ≥3 of nausea, diarrhea, or vomiting and any grade wernickes encephalopathy.

≥3 grade Diarrhea

Group	Value	95% CI
Fedratinib	2
Best Available Therapy (BAT)	0

≥3 grade Nausea

Group	Value	95% CI
Fedratinib	1
Best Available Therapy (BAT)	0

≥3 grade Vomitting

Group	Value	95% CI
Fedratinib	0
Best Available Therapy (BAT)	0

Any Grade Wernickes Encephalopathy

Group	Value	95% CI
Fedratinib	1
Best Available Therapy (BAT)	0

Number of Participants With Thiamine Levels Below the Lower Limit of Normal Secondary · From Cycle 1 Dose 1 to end of Cycle 6, approximately 168 days

Number of participants with thiamine levels below the lower limit of normal

Cycle 1

Group	Value	95% CI
Fedratinib	3
Best Available Therapy (BAT)	0

Cycle 2

Group	Value	95% CI
Fedratinib	13
Best Available Therapy (BAT)	0

Cycle 3

Group	Value	95% CI
Fedratinib	11
Best Available Therapy (BAT)	1

Cycle 4

Group	Value	95% CI
Fedratinib	1
Best Available Therapy (BAT)	0

Cycle 5

Group	Value	95% CI
Fedratinib	1
Best Available Therapy (BAT)	0

Cycle 6

Group	Value	95% CI
Fedratinib	2
Best Available Therapy (BAT)	1

Mean Change in EORTC QOL-C30 at Cycle 7 Day 1 as Compared With Baseline Secondary · from the start of cycle 1 to cycle 7 day 1 approximately 170 days.

QLQ-C30 - The EORTC QLQ-C30 was developed to assess the quality of life of cancer patients. It consists of 30 items classified into 15 domains including 5 functional subscales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning); 3 multi-item symptom subscales (fatigue, nausea/vomiting, and pain); a global QOL subscale; and 6 single items addressing various symptoms and perceived financial impact. Scores vary from 0 (worst) to 100 (best) for the functional dimensions and GHS, and from 0 (best) to 100 (worst) for the symptom dimensions.

Global Heath Status

Group	Value	95% CI
Fedratinib	10.3	± 27.42
Best Available Therapy (BAT)	13.1	± 26.16

Physical Functioning

Group	Value	95% CI
Fedratinib	8.2	± 19.57
Best Available Therapy (BAT)	11.1	± 26.61

Role Functioning

Group	Value	95% CI
Fedratinib	8.1	± 34.26
Best Available Therapy (BAT)	12.7	± 40.79

Emotional Functioning

Group	Value	95% CI
Fedratinib	7.0	± 19.63
Best Available Therapy (BAT)	5.6	± 25.86

Cognitivie Functioning

Group	Value	95% CI
Fedratinib	1.7	± 19.83
Best Available Therapy (BAT)	5.6	± 17.74

Social Functioning

Group	Value	95% CI
Fedratinib	6.5	± 29.18
Best Available Therapy (BAT)	0.0	± 27.89

Fatigue

Group	Value	95% CI
Fedratinib	-15.2	± 29.34
Best Available Therapy (BAT)	-16.4	± 33.81

Nausea and Vomitting

Group	Value	95% CI
Fedratinib	-1.7	± 15.32
Best Available Therapy (BAT)	-9.5	± 28.17

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events, Serious Adverse Events and All Cause Mortality: From first dose to database lock: Approximately 3 years and 8 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fedratinib

Serious: 72/134 (54%)

Deaths: 43/134

Best Available Therapy (BAT)

Serious: 21/67 (31%)

Deaths: 7/67

Fedratinib After Crossover

Serious: 16/46 (35%)

Deaths: 11/46

Serious adverse events (119 terms)

Reaction	System	Fedratinib	Best Available Therapy (BAT)	Fedratinib After Crossover
General physical health deterioration	General disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—
Uveitis	Eye disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—
Multiple organ dysfunction syndrome	General disorders	—	—	—
COVID-19 pneumonia	Infections and infestations	—	—	—
Escherichia sepsis	Infections and infestations	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—
Vitamin B1 deficiency	Metabolism and nutrition disorders	—	—	—
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Chronic kidney disease	Renal and urinary disorders	—	—	—
Renal failure	Renal and urinary disorders	—	—	—

Other adverse events (47 terms — click to expand)

Reaction	System	Fedratinib	Best Available Therapy (BAT)	Fedratinib After Crossover
Diarrhoea	Gastrointestinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Pyrexia	General disorders	—	—	—
Blood creatinine increased	Investigations	—	—	—
Vitamin B1 decreased	Investigations	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—
Glomerular filtration rate decreased	Investigations	—	—	—
Fatigue	General disorders	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
Weight decreased	Investigations	—	—	—
Hyperuricaemia	Metabolism and nutrition disorders	—	—	—
Vitamin B1 deficiency	Metabolism and nutrition disorders	—	—	—
Night sweats	Skin and subcutaneous tissue disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Insomnia	Psychiatric disorders	—	—	—
Chronic kidney disease	Renal and urinary disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Renal failure	Renal and urinary disorders	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—

Most-reported serious reactions: General physical health deterioration, Anaemia, Acute kidney injury, Cardiac failure, Atrial fibrillation, Cardiac failure congestive, COVID-19, Pneumonia.

Data from ClinicalTrials.gov NCT03952039 adverse events section.

Sponsor's own description

A Phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of fedratinib compared to best available therapy (BAT) in subjects with DIPSS (Dynamic International Prognostic Scoring System)-intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF) and previously treated with ruxolitinib. The primary objective of the study is to evaluate the percentage of subjects with at least 35% spleen volume reduction in the fedratinib and the BAT arms.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens.
Hu Q, Bian Q, Rong D, Wang L, et al · · 2023 · cited 190× · PMID 36911202 · DOI 10.3389/fbioe.2023.1110765
Fedratinib, a newly approved treatment for patients with myeloproliferative neoplasm-associated myelofibrosis.
Talpaz M, Kiladjian JJ. · · 2021 · cited 140× · PMID 32647323 · DOI 10.1038/s41375-020-0954-2
Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure.
Harrison CN, Schaap N, Vannucchi AM, Kiladjian JJ, et al · · 2020 · cited 106× · PMID 32129512 · DOI 10.1002/ajh.25777
STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer.
Awasthi N, Liongue C, Ward AC. · · 2021 · cited 97× · PMID 34809691 · DOI 10.1186/s13045-021-01214-y
JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition.
Luo Y, Alexander M, Gadina M, O'Shea JJ, et al · · 2021 · cited 92× · PMID 34625141 · DOI 10.1016/j.jaci.2021.08.004
Myelofibrosis.
Passamonti F, Mora B. · · 2023 · cited 82× · PMID 36416738 · DOI 10.1182/blood.2022017423
Management of myelofibrosis after ruxolitinib failure.
Harrison CN, Schaap N, Mesa RA. · · 2020 · cited 70× · PMID 32198525 · DOI 10.1007/s00277-020-04002-9
Fedratinib in myelofibrosis.
Mullally A, Hood J, Harrison C, Mesa R. · · 2020 · cited 61× · PMID 32343799 · DOI 10.1182/bloodadvances.2019000954

Verify or expand the search:

Other trials of FEDRATINIB

Trials testing the same drug.

NCT03755518 — A Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera My · Phase 3 · terminated

Other recruiting trials for Primary Myelofibrosis

Currently open trials in the same condition.

NCT07228624 — Ruxolitinib Before, During and After Hematopoietic Cell Transplant in Older Patients With Myelofibrosis and Myelodysplas · Phase 2 · recruiting
NCT06661915 — A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs) · Phase 2 · recruiting
NCT06468033 — P1101 in Treating Patients With Early PMF or Overt PMF at Low or Intermediate-1 Risk · Phase 3 · recruiting
NCT06517875 — Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis · Phase 2 · recruiting
NCT06343805 — A Phase 1 Study of AJ1-11095 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF) · Phase 1 · recruiting

Other Celgene trials

Trials by the same sponsor.

NCT07242781 — A Study to Evaluate the Effect of Itraconazole and Rifampin on the Drug Levels of AR-LDD (BMS-986365) in Healthy Adult M · Phase 1 · recruiting
NCT06988488 — A Study to Determine the Recommended Dose and Schedule, and Evaluate the Safety and Preliminary Efficacy of Mezigdomide · Phase 1, PHASE2 · recruiting
NCT06911502 — A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Ch · Phase 3 · recruiting
NCT06808984 — Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986368, for the Treatment of Agitation in Participants W · Phase 2 · recruiting
NCT06782490 — A Study to Evaluate the Efficacy, Safety and Tolerability of BMS-986368 in Participants With Multiple Sclerosis Spastici · Phase 2 · recruiting

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT03952039 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Celgene
Last refreshed: 28 August 2025

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03952039.

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