A study of Momelotinib versus Danazol in Myelofibrosis patients
Research type
Research Study
Full title
A Randomized, Double-Blind, Phase 3 Study to Evaluate the Activity of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic, Anemic Subjects with Primary Myelofibrosis (PMF), Post-Polycythemia Vera (PV) Myelofibrosis, or Post Essential Thrombocythemia (ET) Myelofibrosis who were Previously Treated with JAK Inhibitor Therapy
IRAS ID
270742
Contact name
Donal McLornan
Contact email
Sponsor organisation
Sierra Oncology, Inc.
Eudract number
2019-000583-18
Clinicaltrials.gov Identifier
101155, IND number
Duration of Study in the UK
6 years, 10 months, 17 days
Research summary
Research Summary
Myelofibrosis is a rare condition with an incidence of 0.1 to 1 per 100,000 individuals per year. Symptoms include anaemia, fatigue, night sweats, fever, weight loss, bone pain, pruritus, enlargement of the spleen and liver amongst others. The average age at diagnosis is 67 years, and average survival is 6 years.
The purpose of the study is to compare the effectiveness of the experimental medication momelotinib (MMB) to danazol (DAN) in treating and reducing disease related symptoms, spleen size and the need for blood transfusions in adults with primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.
There is information from previous studies to support the safety and effectiveness of MMB to treat symptoms of myelofibrosis in humans; however, additional information is needed to confirm the findings and to show its ability to reduce the need for transfusions and disease related symptoms. There is also information from previous studies to support the safety and ability of danazol to treat anaemia (decreased red blood cell count). Treatment guidelines recommend danazol for management of anaemia associated with myelofibrosis. Danazol has similar benefits to other medications of its type (anabolic steroids), with fewer side-effects reported in similar conditions.
There may be up to approximately 270 participants and approximately 150 sites taking part in this study. It is anticipated that the study will be carried out at multiple hospitals located in countries in North America, Europe and Asia Pacific.
This is a randomised, double-blind study. Participants will be randomly assigned to receive either MMB and DAN placebo, or DAN and MMB placebo. Neither the study doctor or participant will know which medication they have been assigned to. The double-blind treatment phase will last 24 weeks, and participants may enter an open-label extension phase following this if they choose to.
Summary of Results
Did the participants’ symptoms become less severe after treatment with Momelotinib (MMB)?
Yes. Overall, the researchers found that more participants taking Momelotinib (MMB) had improved MF symptoms after 24 weeks of treatment than those taking Danazol (DAN). To answer this question, the researchers asked the participants to record the severity of their Myelofibrosis (MF) symptoms. They recorded a score based on the severity of their symptoms related to MF using a questionnaire called the Myelofibrosis Symptom Assessment Form Total Symptom Score (MFSAF TSS). The participants answered 7 different questions relating to their MF symptoms. For each question, the participants rated the severity of their symptoms on a scale from 0 (no symptoms) to 10 (the worst symptoms imaginable). The higher the total symptom score, the more severe the participants’ symptoms were.
The researchers reviewed the total symptom scores, and worked out the average change in the participants’ total symptom scores from before they took treatment, to after 24 weeks of treatment. They then counted how many of the participants had at least a 50% decrease in their total symptom scores after 24 weeks of treatment. The more participants who had at least a 50% decrease in their total symptom scores, the more the treatment was helping to manage MF symptoms.
The researchers found that after 24 weeks of treatment:
• 24.6% of the participants who took MMB had at least a 50% decrease in their total symptom score.
• 9.2% of the participants who took DAN had at least a 50% decrease in their total symptom score.
Overall, the researchers found that more of the participants who took MMB had less severe symptoms after treatment compared to those who took DAN.How many participants did not need a blood transfusion after treatment with MMB compared to treatment with DAN?
Overall, the researchers found that after 24 weeks of treatment, the percentage of participants who did not need a blood transfusion was similar between the participants who took MMB and the participants who took DAN. To answer this question, the researchers recorded the number of participants who were transfusion independent after 24 weeks of treatment. This meant they:
• Did not need a blood transfusion (a medical procedure where blood from a different person is infused into the recipient) or have low levels of a protein in the blood called haemoglobin between weeks 12-24 • Had at least 2 tests done by the doctors to check their haemoglobin levels between weeks 12-24 The researchers found that after 24 weeks of treatment:
• 30.0% of the participants who took MMB were transfusion independent.
• 20.0% of the participants who took DAN were transfusion independent.Although a higher percentage of the participants who took MMB were transfusion independent, the researchers found that the difference between treatments was too small to know if MMB increased the number of participants who were transfusion independent compared to DAN. The difference could have been due to chance.
It is important to know that this clinical trial was designed to get the most accurate answers to the questions above. The results in the rest of this section are for another question the researchers wanted to answer to learn more about how well MMB works. This was not the main question this trial was designed to answer.
How many participants had their spleen reduce in size by at least 35.0% after 24 weeks of treatment?
Overall, the researchers found that more participants who took MMB had their spleen reduce in size compared to the participants who took DAN. The spleen is an organ next to the stomach area that helps the immune system to work and can help the body to produce blood cells. The spleen in people with MF is often larger than normal, which can cause discomfort and medical problems.
To answer this question, the researchers counted the number of participants who had their spleen reduce in size by at least 35.0% from before they took treatment to after 24 weeks of treatment. This is called a splenic response rate. Overall, the researchers found that the splenic response rate was higher in the participants who took MMB (23.1%) compared to the participants who took DAN (3.1%).
REC name
East of Scotland Research Ethics Service REC 2
REC reference
19/ES/0136
Date of REC Opinion
3 Dec 2019
REC opinion
Further Information Favourable Opinion