Trial · NCT04603495
Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
NCT04603495, Phase 3, Active not recruiting, Novartis Pharmaceuticals; results first posted 2024-10-28
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2). Trials, record NCT04603495. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04603495
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Phase 3 Study of Pelabresib (CPI-0610) in Myelofibrosis (MF) (MANIFEST-2)
- NCT number
- NCT04603495
- Status
- Active not recruiting
- Phases
- Phase 3
- Enrollment
- 430 participants, actual
- Lead sponsor
- Novartis Pharmaceuticals
- Conditions
- Myelofibrosis, Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis
- Interventions
- Pelabresib, Ruxolitinib, Placebo
- First posted
- 2020-10-26
- Last updated
- 2026-07-17
- Results first posted
- 2024-10-28
Source ClinicalTrials.gov
Registered outcomes25
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Participants With Splenic Response by Central Radiology Reads at Week 24 | Week 24 | Splenic response was characterized by a reduction of at least 35% in spleen volume from baseline (SVR35), as determined by magnetic resonance imaging (MRI) or computerized tomography (CT), and evaluated through a blinded central radiology review at Week 24. |
| Secondary | Key Secondary: Absolute Change From Baseline in Total Symptom Score (TSS) at Week 24 | Baseline, Week 24 | The Total Symptom Score (TSS) at Week 24, compared to baseline, was measured using the Myelofibrosis Symptom Assessment Form v4.0. This score represented the sum of seven individual symptom items, each rated on a 0-10 scale, resulting in a possible total daily score ranging from 0 to 70. A higher TSS reflected a greater disease burden and therefore a worse outcome. The baseline TSS was calculated as the average of non-missing daily total symptom scores over the seven-day period preceding the day of randomization. The TSS for each treatment week was determined as the average of non-missing daily total symptom scores for that week. However, if fewer than four daily scores were available for a given week, the weekly TSS was considered missing. |
| Secondary | Key Secondary: Number of Participants With TSS50 Response at Week 24 | Week 24 | The probability of a TSS response at Week 24 was estimated by calculating the TSS response rate, defined as the percentage of patients who achieved a TSS50 response at Week 24 in each of the two treatment groups. The Total Symptom Score (TSS) response was defined as a ≥50% reduction from baseline in TSS, as measured by the Myelofibrosis Symptom Assessment Form v4.0. |
| Secondary | Percent Change From Baseline in Total Symptom Score (TSS) at Week 24 | Baseline, Week 24 | Percent Change From Baseline in Total Symptom Score (TSS) at Week 24 measured the change in a patient's symptoms after 24 weeks of treatment, relative to baseline. A negative value indicates symptom improvement, and a reduction of ≥50% is typically considered a meaningful clinical response. |
| Secondary | Number of Participants With Improvement From Baseline in Bone Marrow Fibrosis of at Least 1 Grade at Week 24 | Baseline, Week 24 | Improvement in bone marrow fibrosis by at least 1 grade, as assessed by central read compared to baseline, was analyzed by treatment group and overall. The improvement in bone marrow fibrosis grade was defined as a decrease by at least 1 grade in bone marrow fibrosis grade when compared to baseline, where a grade of MF-3 was the most severe, and MF-0 was the least severe. |
| Secondary | Number of Participants With Splenic Response by Central Radiology Reads at Week 48 | Week 48 | Splenic response is characterized by a reduction of at least 35% in spleen volume from baseline (SVR35), as determined by magnetic resonance imaging (MRI) or computerized tomography (CT), and evaluated through a blinded central radiology review at Week 48. |
| Secondary | Number of Participants With TSS50 Response at Week 48 | Week 48 | The probability of a TSS response at Week 48 is estimated by calculating the TSS response rate, defined as the percentage of patients who achieve a TSS50 response at Week 48 in each of the two treatment groups. The Total Symptom Score (TSS) response is defined as a ≥50% reduction from baseline in TSS, as measured by the Myelofibrosis Symptom Assessment Form v4.0. |
| Secondary | Absolute Change From Baseline in Total Symptom Score (TSS) at Week 48 | Baseline, Week 48 | The Total Symptom Score (TSS) at Week 48, compared to baseline, is measured using the Myelofibrosis Symptom Assessment Form v4.0. This score represents the sum of seven individual symptom items, each rated on a 0-10 scale, resulting in a possible total daily score ranging from 0 to 70. A higher TSS reflects a greater disease burden and therefore a worse outcome. The baseline TSS is calculated as the average of non-missing daily total symptom scores over the seven-day period preceding the day of randomization. The TSS for each treatment week is determined as the average of non-missing daily total symptom scores for that week. However, if fewer than four daily scores are available for a given week, the weekly TSS is considered missing. |
| Secondary | Rate of Red Blood Cell (RBC) Transfusion Over First 24 Weeks of Treatment | Week 24 | The rate of RBC transfusions was defined as the average number of RBC units transfused per patient month (4 weeks) during the first 24 weeks of treatment. The average number of RBC units per patient-month was calculated by dividing the total (ie, for all patients) number of RBC units in the whole exposure time by the sum of patient-months. |
| Secondary | Number of Participants Who Transitioned From Red Blood Cell (RBC) Transfusion Dependence to Transfusion Independence | From 12-week baseline period prior to dosing to any 12-week period post baseline, up to 24 weeks | Transfusion dependence (TD) was defined as having received ≥6 units of RBCs during the 12-week baseline period prior to dosing and Transfusion independence (TI) was defined as the absence of RBC transfusions during any continuous 12-week period of the double-blind treatment phase. The conversion from TD to TI was evaluated and defined as the proportion of patients who transitioned from transfusion dependence to transfusion independence. Patients who remained in the double-blind treatment period and had not received any RBC transfusions during the most recent 12 weeks were considered responders. Patients who discontinued from the double-blind treatment before Week 12 were classified as non-responders. |
1 to 10 of 25Source ClinicalTrials.gov
See all 25 registered outcomesOutcomes25
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Participants With Splenic Response by Central Radiology Reads at Week 24 | Week 24 | Intent-to-Treat (ITT) Analysis Set | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Key Secondary: Absolute Change From Baseline in Total Symptom Score (TSS) at Week 24 | Baseline, Week 24 | Intent-to-Treat (ITT) Analysis Set | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Key Secondary: Number of Participants With TSS50 Response at Week 24 | Week 24 | Intent-to-Treat (ITT) Analysis Set | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Percent Change From Baseline in Total Symptom Score (TSS) at Week 24 | Baseline, Week 24 | Intent-to-Treat (ITT) Analysis Set | Percent change from baseline to Week 24 | MEAN |
| SECONDARY | Number of Participants With Improvement From Baseline in Bone Marrow Fibrosis of at Least 1 Grade at Week 24 | Baseline, Week 24 | Intent-to-Treat (ITT) Analysis Set: Only participants with available data at the specified time point were included in the analysis. | Participants | COUNT_OF_PARTICIPANTS |
| SECONDARY | Number of Participants With Splenic Response by Central Radiology Reads at Week 48 | Week 48 | |||
| SECONDARY | Number of Participants With TSS50 Response at Week 48 | Week 48 | |||
| SECONDARY | Absolute Change From Baseline in Total Symptom Score (TSS) at Week 48 | Baseline, Week 48 | |||
| SECONDARY | Rate of Red Blood Cell (RBC) Transfusion Over First 24 Weeks of Treatment | Week 24 | Intent-to-Treat (ITT) Analysis Set | RBC units transfused/patient-months | NUMBER |
| SECONDARY | Number of Participants Who Transitioned From Red Blood Cell (RBC) Transfusion Dependence to Transfusion Independence | From 12-week baseline period prior to dosing to any 12-week period post baseline, up to 24 weeks | Intent-to-Treat (ITT) Analysis Set | Participants | COUNT_OF_PARTICIPANTS |
1 to 10 of 25Source ClinicalTrials.gov
See all 25 outcomesResults by group30
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Participants With Splenic Response by Central Radiology Reads at Week 24 | Pelabresib + Ruxolitinib (Experimental Arm) | 141 | Participants | ||
| Number of Participants With Splenic Response by Central Radiology Reads at Week 24 | Placebo + Ruxolitinib (Control Arm) | 76 | Participants | ||
| Key Secondary: Absolute Change From Baseline in Total Symptom Score (TSS) at Week 24 | Pelabresib + Ruxolitinib (Experimental Arm) | -15.99 | Standard Error 1.028 | score on a scale | |
| Key Secondary: Absolute Change From Baseline in Total Symptom Score (TSS) at Week 24 | Placebo + Ruxolitinib (Control Arm) | -14.05 | Standard Error 0.986 | score on a scale | |
| Key Secondary: Number of Participants With TSS50 Response at Week 24 | Pelabresib + Ruxolitinib (Experimental Arm) | 112 | Participants | ||
| Key Secondary: Number of Participants With TSS50 Response at Week 24 | Placebo + Ruxolitinib (Control Arm) | 100 | Participants | ||
| Percent Change From Baseline in Total Symptom Score (TSS) at Week 24 | Pelabresib + Ruxolitinib (Experimental Arm) | -50.3 | 95% Confidence Interval -56.6 to -44.0 | Percent change from baseline to Week 24 | |
| Percent Change From Baseline in Total Symptom Score (TSS) at Week 24 | Placebo + Ruxolitinib (Control Arm) | -45.9 | 95% Confidence Interval -51.8 to -40.0 | Percent change from baseline to Week 24 | |
| Number of Participants With Improvement From Baseline in Bone Marrow Fibrosis of at Least 1 Grade at Week 24 | Pelabresib + Ruxolitinib (Experimental Arm) | 36 | Participants | ||
| Number of Participants With Improvement From Baseline in Bone Marrow Fibrosis of at Least 1 Grade at Week 24 | Placebo + Ruxolitinib (Control Arm) | 21 | Participants |
1 to 10 of 30Source ClinicalTrials.gov
See all 30 results by groupParticipant flow22
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Pelabresib + Ruxolitinib (Experimental Arm) | 214 | |
| Overall Study | STARTED | Placebo + Ruxolitinib (Control Arm) | 216 | |
| Overall Study | Modified Intent-to-Treat (mITT) Analysis Set | Pelabresib + Ruxolitinib (Experimental Arm) | 212 | |
| Overall Study | Modified Intent-to-Treat (mITT) Analysis Set | Placebo + Ruxolitinib (Control Arm) | 214 | |
| Overall Study | Safety Analysis Set | Pelabresib + Ruxolitinib (Experimental Arm) | 212 | |
| Overall Study | Safety Analysis Set | Placebo + Ruxolitinib (Control Arm) | 214 | |
| Overall Study | Per-Protocol Set (PP Set) | Pelabresib + Ruxolitinib (Experimental Arm) | 196 | |
| Overall Study | Per-Protocol Set (PP Set) | Placebo + Ruxolitinib (Control Arm) | 194 | |
| Overall Study | Pharmacokinetic (PK) Analysis Set | Pelabresib + Ruxolitinib (Experimental Arm) | 212 | |
| Overall Study | Pharmacokinetic (PK) Analysis Set | Placebo + Ruxolitinib (Control Arm) | 211 |
1 to 10 of 22Source ClinicalTrials.gov
See all 22 participant flowAdverse events328
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Pelabresib + Ruxolitinib (Experimental Arm) | 90 | 212 | |
| other | Anaemia | Blood and lymphatic system disorders | Placebo + Ruxolitinib (Control Arm) | 116 | 214 | |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Pelabresib + Ruxolitinib (Experimental Arm) | 68 | 212 | |
| other | Thrombocytopenia | Blood and lymphatic system disorders | Placebo + Ruxolitinib (Control Arm) | 50 | 214 | |
| other | Constipation | Gastrointestinal disorders | Pelabresib + Ruxolitinib (Experimental Arm) | 39 | 212 | |
| other | Constipation | Gastrointestinal disorders | Placebo + Ruxolitinib (Control Arm) | 52 | 214 | |
| other | Diarrhoea | Gastrointestinal disorders | Pelabresib + Ruxolitinib (Experimental Arm) | 49 | 212 | |
| other | Diarrhoea | Gastrointestinal disorders | Placebo + Ruxolitinib (Control Arm) | 39 | 214 | |
| other | Nausea | Gastrointestinal disorders | Pelabresib + Ruxolitinib (Experimental Arm) | 30 | 212 | |
| other | Nausea | Gastrointestinal disorders | Placebo + Ruxolitinib (Control Arm) | 32 | 214 |
1 to 10 of 328Source ClinicalTrials.gov
See all 328 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Pelabresib + Ruxolitinib (Experimental Arm) | 11 | 212 |
| Total, all-cause mortality | Placebo + Ruxolitinib (Control Arm) | 10 | 214 |
| Total, other adverse events | Pelabresib + Ruxolitinib (Experimental Arm) | 201 | 212 |
| Total, other adverse events | Placebo + Ruxolitinib (Control Arm) | 204 | 214 |
| Total, serious adverse events | Pelabresib + Ruxolitinib (Experimental Arm) | 63 | 212 |
| Total, serious adverse events | Placebo + Ruxolitinib (Control Arm) | 63 | 214 |
Source ClinicalTrials.gov
Papers2
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons7
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Pelabresib + Ruxolitinib (Experimental Arm) vs Placebo + Ruxolitinib (Control Arm): Key Secondary: Number of Participants With TSS50 Response at Week 24 | Trial comparisons |
| Pelabresib + Ruxolitinib (Experimental Arm) vs Placebo + Ruxolitinib (Control Arm): Number of Participants With Splenic Response by Central Radiology Reads at Week 24 | Trial comparisons |
| Pelabresib + Ruxolitinib (Experimental Arm) vs Placebo + Ruxolitinib (Control Arm): Number of Participants With Improvement From Baseline in Bone Marrow Fibrosis of at Least 1 Grade at Week 24 | Trial comparisons |
| Pelabresib + Ruxolitinib (Experimental Arm) vs Placebo + Ruxolitinib (Control Arm): Number of Participants With Modified Total Symptom Score (mTSS) Response at Week 24 | Trial comparisons |
| Pelabresib + Ruxolitinib (Experimental Arm) vs Placebo + Ruxolitinib (Control Arm): Number of Participants Who Transitioned From Red Blood Cell (RBC) Transfusion Dependence to Transfusion Independence | Trial comparisons |
| Pelabresib + Ruxolitinib (Experimental Arm) vs Placebo + Ruxolitinib (Control Arm): deaths from any cause | Trial comparisons |
| Pelabresib + Ruxolitinib (Experimental Arm) vs Placebo + Ruxolitinib (Control Arm): serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT04603495
GET https://conductscience.org/api/trials/v1/NCT04603495/registered?page=2