A Phase 3 interventional study of Momelotinib and Placebo to match danazol in Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis and Post-essential Thrombocythemia Myelofibrosis, sponsored by Sierra Oncology LLC - a GSK company. Completed at 167 sites in 22 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-11-01.
Sponsored by Sierra Oncology LLC - a GSK company (part of GlaxoSmithKline) · Phase 3, Interventional, and Treatment
MOMENTUM is a randomized, double-blind, active control Phase 3 trial intended to confirm the differentiated clinical benefits of the investigational drug momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic participants who have previously received an approved Janus kinase inhibitor (JAKi) therapy for myelofibrosis (MF). The purpose of this clinical study is to compare the effectiveness and safety of MMB to DAN in treating and reducing: 1) disease related symptoms, 2) the need for blood transfusions and 3) splenomegaly, in adults with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The study is planned in countries including, but not limited to: Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Romania, Singapore, South Korea, Spain, Sweden, Taiwan, United Kingdom (UK) and United States (US).
Participants must be symptomatic with a Myelofibrosis Symptom Assessment Form (MFSAF) version (v) 4.0 Total Symptom Score of >= 10 at screening, and be anemic with hemoglobin (Hgb) \< 10 gram/deciliter (g/dL). For participants with ongoing JAKi therapy at screening, JAKi therapy must be tapered over a period of at least 1 week, followed by a 2-week non-treatment washout interval prior to randomization.
Participants will be randomized 2:1 to orally self-administer blinded treatment: MMB plus placebo or DAN plus placebo. Participants randomized to receive MMB who complete the randomized treatment period to the end of Week 24 may continue to receive MMB in the open-label extended treatment period to the end of Week 204 (a total period of treatment of approximately 4 years) if the participants tolerates and continues to benefit from MMB.
Participants randomized to receive DAN may cross-over to MMB open-label treatment in the following circumstances: at the end of Week 24 if they complete the randomized treatment period; or at the end of Week 24 if they discontinue treatment with DAN but continue study assessments and do not receive prohibited medications including alternative active anti-MF therapy; or at any time during the randomized treatment period if they meet the protocol-defined criteria for radiographically confirmed symptomatic splenic progression. Participants randomized to receive DAN who are receiving clinical benefit at the end of Week 24 may choose to continue DAN therapy up to Week 48. The comparator treatment, DAN, is an approved medication in the US and in some other countries and is recommended by national guidelines as a treatment for anemia in MF.
MOMENTUM Contact Email: GSKClinicalSupportHD@gsk.com
625 studies on the registry are indexed under Primary Myelofibrosis; 124 are open to participants now.
This study's enrollment of 195 is above the median of 43 across 489 interventional studies indexed under Primary Myelofibrosis.
Browse Primary Myelofibrosis studies →Sierra Oncology LLC - a GSK company is the lead sponsor of 19 studies on the registry; none are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 5 (63%) have results posted.
First submitted before Sierra Oncology LLC became part of GlaxoSmithKline.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Acceptable laboratory assessments:
Exclusion Criteria:
Use of the following treatments within the time periods noted:
Any of the following (criteria a - k):
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive momelotinib plus placebo to match danazol
Drug: Momelotinib · Drug: Placebo to match danazol
Participants will receive danazol plus placebo to match momelotinib
Drug: Danazol · Drug: Placebo to match momelotinib
Momelotinib tablets will be self-administered orally once daily
Also known as: MMB, GS-0387, CYT387
Danazol placebo capsules will be self-administered orally twice daily
Danazol capsules will be self-administered orally twice daily
Also known as: Danocrine
Momelotinib placebo tablets will be self-administered orally once daily
Total Symptom Score (TSS) Response Rate at Week 24
Myelofibrosis Symptom Assessment Form (MFSAF) TSS version (v) 4.0 response rate was defined as percentage of participants with a \>= 50 percent (%) reduction from Baseline in mean MFSAF TSS over consecutive 28-day period immediately before end of Week 24. TSS response rate was measured using MFSAF v4.0. MFSAF v4.0 comprises 7 domains representing 7 most relevant symptoms of myelofibrosis (MF) identified through existing participant and clinician-based evidence: fatigue,night sweats,pruritus,abdominal discomfort,pain under left ribs,early satietyand bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0(absent) to 10(worst imaginable). The MFSAF TSS was calculated as sum of scores of 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date.
Time frame: Baseline and Week 24
Percentage of Participants With Transfusion Independence (TI) at Week 24
TI status was defined as not receiving red blood cell (RBC) or whole blood transfusion for \>=12 weeks, with no hemoglobin (Hgb) level \< 8 grams per deciliter (g/dL) during the same interval. Percentage of participants with TI have been presented.
Time frame: Week 24
Splenic Response Rate (SRR) of >=25% at Week 24
Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of \>=25% from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
Time frame: Baseline and Week 24
Change From Baseline in MFSAF TSS at Week 24
TSS was measured using the MFSAF v4.0. The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). The MFSAF TSS was calculated as the sum of scores of the 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Time frame: Baseline and Week 24
Splenic Response Rate (SRR) of >= 35% at Week 24
Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of \>=35 % from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
Time frame: Baseline and Week 24
Percentage of Participants With Zero RBC Units Transfused Over 24-Weeks
Percentage of participants with zero RBC units transfused over 24-weeks were reported.
Time frame: Up to 24 weeks
Percentage of Participants With <=4 RBC Units Transfused Over 24-weeks
Percentage of participants with \<=4 RBC units transfused over 24-weeks were reported.
Time frame: Up to 24 weeks
Duration of MFSAF TSS Response
Duration of MFSAF TSS response is defined as the number of days from the start of the initial 28-day period in which a participant had a \>= 50% reduction from Baseline TSS to the first day of the 7-day assessment that determines the mean TSS for the 28-day period during which the participants TSS equals or exceeds their Baseline value.
Time frame: Up to a maximum of 151 weeks
Duration of TI Response
Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level \< 8 g/dL (except in the case of clinically overt bleeding).
Time frame: Up to a maximum of 151 weeks
Mean Cumulative Number of Whole Blood Units Transfused Over 24 Weeks
Cumulative transfusion risk was calculated as the estimated mean cumulative number of whole blood units transfused during the study.
Time frame: Up to Week 24
Percentage of Participants With Transfusion Dependence (TD) Status at Week 24
TD status at Week 24 is defined as requirement of \>=4 RBC units in an 8-week period immediately prior to the end of Week 24.
Time frame: Week 24
Percentage of Participants With a Hemoglobin Response
Hemoglobin responses are defined as increases of \>= 1, \>= 1.5, or \>= 2 g/dL from Baseline in Hgb, as measured over a (rolling) period of at least 12 consecutive weeks falling entirely before the end of Week 24. Baseline was the last assessment done before or on the day of first dose date. Data has been reported for percentage of participants who had \>= 1, \>= 1.5, or \>= 2 g/dL increase from Baseline in hemoglobin.
Time frame: Baseline and Week 24
Number of Baseline TD Participants With TI Status at Week 24
Participants were defined as having TD if they met both of the following requirements in the 8 weeks immediately before the end of Week 24: \>= 4 red blood cell or whole blood units were transfused (except in the case of clinically overt bleeding), each in response to a hemoglobin assessment of \<= 9.5 g/dL; and there were \>= 2 hemoglobin assessments with \>= 28 days between the earliest and latest hemoglobin assessments. TI status was defined as not requiring red blood cell transfusion (except in the case of clinically overt bleeding) for \>= 12 weeks immediately prior to the end of Week 24, with hemoglobin levels \>= 8 g/dL.
Time frame: Week 24
Duration of TI in Baseline TD Participants
Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level \< 8 g/dL (except in the case of clinically overt bleeding).
Time frame: Up to a maximum of 151 weeks
Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- up to Week 24
An adverse event (AE) is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
Time frame: Up to Week 24
Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- From Week 24 to a Maximum of 151 Weeks
An AE is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
Time frame: From Week 24 to a maximum of 151 weeks
Overall Survival (OS)
Overall survival is defined as the interval from the first study drug dosing date (or randomization date for participants who did not receive treatment) to death from any cause.
Time frame: Up to a maximum of 151 weeks
Leukemia-free Survival (LFS)
LFS is defined as the interval from first study drug dosing date (or randomization date for participants who did not receive treatment) to any evidence of leukemic transformation and/or death (from any cause).
Time frame: Up to a maximum of 151 weeks
Change From Baseline in Disease-related Fatigue as Assessed by MFSAF TSS v4.0 at Week 24
The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant- and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). Data has been reported for Disease-related Fatigue domain measured using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable), higher score indicates worst outcome. An increase in score from Baseline indicated a worsening of fatigue and a decrease in score from Baseline indicated an improvement in fatigue. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Time frame: Baseline and Week 24
Change From Baseline in Cancer-related Fatigue as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at Week 24
The EORTC QLQ-C30 is comprised of 5 functional scales (physical, role, emotional, social, cognitive), eight single item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea), as well as sub-scales assessing global health/quality of life and financial impact. Most items use a 4-point Likert scale from "not at all" to "very much" and a one-week recall period with the exception of the final two items which use a 7 point scale response from "very poor" to "excellent". Scores were averaged and transformed to a 0-100 scale, with higher scores representing better functioning/quality of life. An increase in scores from Baseline indicated an improved functioning/quality of life, and a decrease in scores from Baseline indicated a worsened functioning/quality of life. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Time frame: Baseline and Week 24
Change From Baseline in Physical Function Score as Assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b at Week 24
PROMIS Physical Function Short Form 10b consists of 14 questions; each with a 5-point response. PROMIS short form assesses self-reported capability of a participant rather than actual performance of physical activities. This includes functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back) as well as instrumental activities of daily living, such as running errands. Participants scored each response on a scale from 1 (unable to do) to 5 (without any difficulty, or not at all). Total possible range of scores was 14 to 70, with higher scores corresponding to a greater physical function ability. An increase in score from Baseline indicated an improvement in physical function ability and a decrease in score from Baseline indicated a reduction in physical function ability. Baseline was last assessment done before or on the day of first dose date. Change from Baseline was defined as post-Baseline value minus Baseline value.
Time frame: Baseline and Week 24
This study evaluated the activity of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic, Anemic participants. This study consists of Randomized Double-blind (DB) Treatment Period (TP) and Open-label extended Treatment Period.
| Milestone | MMB 200 mg Once Daily (QD) + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Started | 130 | 65 |
| Completed | 94 | 38 |
| Not completed | 36 | 27 |
| Withdrew: Adverse event | 16 | 11 |
| Withdrew: Withdrawal by subject | 6 | 5 |
| Withdrew: Lack of efficacy | 6 | 3 |
| Withdrew: Death | 4 | 3 |
| Withdrew: Leukemic transformation | 2 | 2 |
| Withdrew: Disease progression | 1 | 2 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Physician decision | 0 | 1 |
| Milestone | MMB 200 mg Once Daily (QD) + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Started | 93 | 41 |
| Completed | 0 | 0 |
| Not completed | 93 | 41 |
| Withdrew: Adverse event | 11 | 1 |
| Withdrew: Death | 6 | 3 |
| Withdrew: Lack of efficacy | 6 | 2 |
| Withdrew: Physician decision | 4 | 3 |
| Withdrew: Withdrawal by subject | 4 | 3 |
| Withdrew: Leukemic transformation | 0 | 1 |
| Withdrew: Disease progression | 1 | 1 |
| Withdrew: Continuing in mmb extension study | 61 | 27 |
Myelofibrosis Symptom Assessment Form (MFSAF) TSS version (v) 4.0 response rate was defined as percentage of participants with a \>= 50 percent (%) reduction from Baseline in mean MFSAF TSS over consecutive 28-day period immediately before end of Week 24. TSS response rate was measured using MFSAF v4.0. MFSAF v4.0 comprises 7 domains representing 7 most relevant symptoms of myelofibrosis (MF) identified through existing participant and clinician-based evidence: fatigue,night sweats,pruritus,abdominal discomfort,pain under left ribs,early satietyand bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0(absent) to 10(worst imaginable). The MFSAF TSS was calculated as sum of scores of 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date.
| Percentage of participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Total Symptom Score (TSS) Response Rate at Week 24 | 24.62 (17.49 to 32.94) | 9.23 (3.46 to 19.02) |
TI status was defined as not receiving red blood cell (RBC) or whole blood transfusion for \>=12 weeks, with no hemoglobin (Hgb) level \< 8 grams per deciliter (g/dL) during the same interval. Percentage of participants with TI have been presented.
| Percentage of Participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Percentage of Participants With Transfusion Independence (TI) at Week 24 | 30.0 (22.28 to 38.66) | 20.00 (11.10 to 31.77) |
Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of \>=25% from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
| Percentage of Participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Splenic Response Rate (SRR) of >=25% at Week 24 | 39.23 (30.79 to 48.18) | 6.15 (1.70 to 15.01) |
TSS was measured using the MFSAF v4.0. The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). The MFSAF TSS was calculated as the sum of scores of the 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
| Scores on a scale | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Change From Baseline in MFSAF TSS at Week 24 | -9.36 ± 1.08 | -3.13 ± 1.62 |
Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of \>=35 % from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
| Percentage of Participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Splenic Response Rate (SRR) of >= 35% at Week 24 | 22.31 (15.48 to 30.44) | 3.08 (0.37 to 10.68) |
Percentage of participants with zero RBC units transfused over 24-weeks were reported.
| Percentage of participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Percentage of Participants With Zero RBC Units Transfused Over 24-Weeks | 35.38 (27.20 to 44.25) | 16.92 (8.76 to 28.27) |
Percentage of participants with \<=4 RBC units transfused over 24-weeks were reported.
| Percentage of participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Percentage of Participants With <=4 RBC Units Transfused Over 24-weeks | 55.38 (46.42 to 64.10) | 44.62 (32.27 to 57.47) |
Duration of MFSAF TSS response is defined as the number of days from the start of the initial 28-day period in which a participant had a \>= 50% reduction from Baseline TSS to the first day of the 7-day assessment that determines the mean TSS for the 28-day period during which the participants TSS equals or exceeds their Baseline value.
| Days | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Duration of MFSAF TSS Response | 286.00 (286.00 to 286.00) | NA (NA to NA) |
Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level \< 8 g/dL (except in the case of clinically overt bleeding).
| Days | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Duration of TI Response | NA (NA to NA) | NA (NA to NA) |
Cumulative transfusion risk was calculated as the estimated mean cumulative number of whole blood units transfused during the study.
| Whole blood units | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Mean Cumulative Number of Whole Blood Units Transfused Over 24 Weeks | 6.55 ± 8.413 | 10.86 ± 13.203 |
TD status at Week 24 is defined as requirement of \>=4 RBC units in an 8-week period immediately prior to the end of Week 24.
| Percentage of participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Percentage of Participants With Transfusion Dependence (TD) Status at Week 24 | 15.38 (9.66 to 22.76) | 24.62 (14.77 to 36.87) |
Hemoglobin responses are defined as increases of \>= 1, \>= 1.5, or \>= 2 g/dL from Baseline in Hgb, as measured over a (rolling) period of at least 12 consecutive weeks falling entirely before the end of Week 24. Baseline was the last assessment done before or on the day of first dose date. Data has been reported for percentage of participants who had \>= 1, \>= 1.5, or \>= 2 g/dL increase from Baseline in hemoglobin.
| Percentage of participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| >=1g/dL Increase | 53.08 (44.13 to 61.88) | 33.85 (22.57 to 46.65) |
| >=1.5g/dL Increase | 40.00 (31.51 to 48.95) | 23.08 (13.53 to 35.19) |
| >=2g/dL Increase | 29.23 (21.59 to 37.85) | 20.00 (11.10 to 31.77) |
Participants were defined as having TD if they met both of the following requirements in the 8 weeks immediately before the end of Week 24: \>= 4 red blood cell or whole blood units were transfused (except in the case of clinically overt bleeding), each in response to a hemoglobin assessment of \<= 9.5 g/dL; and there were \>= 2 hemoglobin assessments with \>= 28 days between the earliest and latest hemoglobin assessments. TI status was defined as not requiring red blood cell transfusion (except in the case of clinically overt bleeding) for \>= 12 weeks immediately prior to the end of Week 24, with hemoglobin levels \>= 8 g/dL.
| Participants | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Number of Baseline TD Participants With TI Status at Week 24 | 9 | 3 |
Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level \< 8 g/dL (except in the case of clinically overt bleeding).
| Days | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Duration of TI in Baseline TD Participants | NA (224.0 to NA) | NA (196.0 to NA) |
An adverse event (AE) is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
| Participants | MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period | DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period |
|---|---|---|
| Any non-SAEs | 108 | 55 |
| Any SAEs | 45 | 26 |
An AE is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
| Participants | MMB 200 mg QD- Open-Label Extended Treatment Period | DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period |
|---|---|---|
| Any non-SAEs | 57 | 28 |
| Any SAEs | 30 | 12 |
Overall survival is defined as the interval from the first study drug dosing date (or randomization date for participants who did not receive treatment) to death from any cause.
| Days | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Overall Survival (OS) | 624.0 (333.0 to NA) | NA (309.00 to NA) |
LFS is defined as the interval from first study drug dosing date (or randomization date for participants who did not receive treatment) to any evidence of leukemic transformation and/or death (from any cause).
| Days | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Leukemia-free Survival (LFS) | 624.0 (325.0 to NA) | NA (284.0 to NA) |
The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant- and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). Data has been reported for Disease-related Fatigue domain measured using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable), higher score indicates worst outcome. An increase in score from Baseline indicated a worsening of fatigue and a decrease in score from Baseline indicated an improvement in fatigue. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
| Scores on a scale | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Change From Baseline in Disease-related Fatigue as Assessed by MFSAF TSS v4.0 at Week 24 | -1.53 ± 0.20 | -0.82 ± 0.31 |
The EORTC QLQ-C30 is comprised of 5 functional scales (physical, role, emotional, social, cognitive), eight single item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea), as well as sub-scales assessing global health/quality of life and financial impact. Most items use a 4-point Likert scale from "not at all" to "very much" and a one-week recall period with the exception of the final two items which use a 7 point scale response from "very poor" to "excellent". Scores were averaged and transformed to a 0-100 scale, with higher scores representing better functioning/quality of life. An increase in scores from Baseline indicated an improved functioning/quality of life, and a decrease in scores from Baseline indicated a worsened functioning/quality of life. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
| Scores on a scale | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Change From Baseline in Cancer-related Fatigue as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at Week 24 | -14.34 ± 2.35 | -3.52 ± 3.65 |
PROMIS Physical Function Short Form 10b consists of 14 questions; each with a 5-point response. PROMIS short form assesses self-reported capability of a participant rather than actual performance of physical activities. This includes functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back) as well as instrumental activities of daily living, such as running errands. Participants scored each response on a scale from 1 (unable to do) to 5 (without any difficulty, or not at all). Total possible range of scores was 14 to 70, with higher scores corresponding to a greater physical function ability. An increase in score from Baseline indicated an improvement in physical function ability and a decrease in score from Baseline indicated a reduction in physical function ability. Baseline was last assessment done before or on the day of first dose date. Change from Baseline was defined as post-Baseline value minus Baseline value.
| Scores on a scale | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo |
|---|---|---|
| Change From Baseline in Physical Function Score as Assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b at Week 24 | 1.19 ± 0.77 | -0.11 ± 1.21 |
Collected over All-cause mortality, Serious adverse events (SAEs) and non-SAEs were collected up to Week 24 for Randomized Double-Blind Treatment Period and From Week 24 to a maximum of 151 weeks for the Open-Label Extended Treatment Period. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period | 25/130 (19.2%) | 45/130 (34.6%) | 108/130 (83.1%) |
| DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period | 16/65 (24.6%) | 26/65 (40%) | 55/65 (84.6%) |
| MMB 200 mg QD- Open-Label Extended Treatment Period | 23/93 (24.7%) | 30/93 (32.3%) | 57/93 (61.3%) |
| DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period | 8/41 (19.5%) | 12/41 (29.3%) | 28/41 (68.3%) |
| Event | MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period | DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period | MMB 200 mg QD- Open-Label Extended Treatment Period | DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period |
|---|---|---|---|---|
| PneumoniaInfections and infestations | 3/130 | 6/65 | 1/93 | 1/41 |
| Acute kidney injuryRenal and urinary disorders | 4/130 | 3/65 | 2/93 | 2/41 |
| AnaemiaBlood and lymphatic system disorders | 5/130 | 3/65 | 1/93 | 1/41 |
| COVID-19 pneumoniaInfections and infestations | 3/130 | 0/65 | 4/93 | 0/41 |
| Splenic infarctionBlood and lymphatic system disorders | 1/130 | 2/65 | 1/93 | 0/41 |
| General physical health deteriorationGeneral disorders | 2/130 | 2/65 | 1/93 | 0/41 |
| Transformation to acute myeloid leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 3/130 | 2/65 | 0/93 | 1/41 |
| Acute myocardial infarctionCardiac disorders | 1/130 | 0/65 | 0/93 | 1/41 |
| PyrexiaGeneral disorders | 3/130 | 0/65 | 1/93 | 1/41 |
| Sudden deathGeneral disorders | 1/130 | 0/65 | 0/93 | 1/41 |
| Event | MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period | DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period | MMB 200 mg QD- Open-Label Extended Treatment Period | DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period |
|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 29/130 | 6/65 | 16/93 | 5/41 |
| ThrombocytopeniaBlood and lymphatic system disorders | 28/130 | 7/65 | 13/93 | 7/41 |
| Weight decreasedInvestigations | 14/130 | 3/65 | 9/93 | 7/41 |
| NauseaGastrointestinal disorders | 21/130 | 6/65 | 8/93 | 0/41 |
| Blood creatinine increasedInvestigations | 10/130 | 10/65 | 7/93 | 4/41 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 9/130 | 10/65 | 7/93 | 0/41 |
| Oedema peripheralGeneral disorders | 9/130 | 9/65 | 3/93 | 1/41 |
| AstheniaGeneral disorders | 17/130 | 6/65 | 12/93 | 0/41 |
| PyrexiaGeneral disorders | 11/130 | 5/65 | 12/93 | 3/41 |
| HypertensionVascular disorders | 6/130 | 6/65 | 3/93 | 5/41 |
Baseline characteristics were measured in the Intention-To-Treat (ITT) Analysis Set, which included all randomized participants.
| Age, Continuous(Years) | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo | Total |
|---|---|---|---|
| Mean | 69.85 ± 8.24 | 71.46 ± 6.99 | 70.38 ± 7.86 |
| Sex: Female, Male(Participants) | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo | Total |
|---|---|---|---|
| Female | 51 | 21 | 72 |
| Male | 79 | 44 | 123 |
| Ethnicity (NIH/OMB)(Participants) | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 5 | 6 | 11 |
| Not Hispanic or Latino | 115 | 54 | 169 |
| Unknown or Not Reported | 10 | 5 | 15 |
| Race (NIH/OMB)(Participants) | MMB 200 mg QD + Placebo | DAN 300 mg BID + Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 12 | 6 | 18 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 2 | 4 |
| White | 107 | 50 | 157 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 9 | 7 | 16 |
Showing the first 100 of 167 sites across 22 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Feb 2020 to primary completion in Dec 2021, 21 months.
Results were first posted in Dec 2022, 1 year after primary completion.
Of 22 phase 3 interventional studies under Primary Myelofibrosis, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 30 and three quarters within 68. This study's 21 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Momelotinib
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