* Magrolimab + Azacitidine versus Azacitidine + Placebo in Untreated MDS
Research type
Research Study
Full title
ENHANCE:A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in Combination with Azacitidine versus Azacitidine Plus Placebo in Treatment-naïve Patients with Higher Risk Myelodysplastic Syndrome
IRAS ID
291974
Contact name
Paresh Vyas
Contact email
Sponsor organisation
Gilead Sciences, Inc.
Eudract number
2020-004287-26
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 0 months, 1 days
Research summary
Research Summary
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study investigating magrolimab + azacitidine compared to azacitidine + placebo in previously untreated patients with intermediate/high/very high risk myelodysplastic syndrome (MDS) by Revised International Prognostic Scoring System (IPSS-R).
Novel therapies that can be combined with hypomethylating agents while maintaining an acceptable safety profile and improving durable complete remissions or survival probability are needed for individuals with higher risk MDS. No new therapies have been approved in MDS for over a decade, which underscores a high unmet medical need in this population. Patients with MDS experience frequent comorbidities and mortalities as a result of cytopenias due to the disease and to hypomethylating agents. The need for combination therapies that can induce hematologic improvement and disease remission leading to a clear clinical benefit is quite evident. Magrolimab in combination with azacitidine is being developed in previously untreated patients with intermediate/high/very high risk MDS by IPSS-R to improve clinical activity and maintain an acceptable safety profile. The target population will include previously untreated patients, 18 and over years of age with MDS defined according to World Health Organization classification with an IPSS-R risk category of intermediate, high, or very high risk. Approximately 520 patients will be recruited globally.
Magrolimab + azacitidine or azacitidine + placebo will be administered, in 28-day cycles dependent on randomisation.
The length of participation on the study including screening and follow-up will be up to 4 years after the last patient is randomised. Patients will remain on treatment until disease progression, loss of clinical benefit or unacceptable toxicities occur.
There will be approximately 200 sites in the United States, Australia, Europe and other countries as required taking part in this study based on enrollment and study timelines.Summary of Results
The purpose of this clinical study is to find out how magrolimab plus azacitidine works in untreated participants with higher risk myelodysplastic syndromes (MDS) by IPSS-R. This is compared to the treatment of placebo plus azacitidine. IPSS-R: It stands for Revised International Prognostic Scoring System. The prognostic scoring system helps to find out the prognosis (likely outcome) of MDS. The score is based on various factors and categorize people with MDS in 5 risk categories: very low, low, intermediate, high or very high risk MDS. The researchers added placebo to azacitidine so that the participants would not know which treatment they were receiving. The placebo looked like magrolimab.
The main questions the researchers wanted to answer in this study were:
• How many participants achieved complete remission?
• How long did participants live for after joining the study?
• What side effects did participants have during the study, if any?In total, 539 participants living with MDS around the world took part in this study.
The researchers wanted to find out how many participants achieved complete remission after taking the study treatment. The participants had blood tests and bone marrow tests done during the study. The doctors checked the results of these tests. If test results showed that there was a rise in healthy blood cells and if the blast cells almost disappeared, the participants were said to have achieved complete remission. The percentage of participants with complete remission was less in participants who received magrolimab plus azacitidine compared with participants who received placebo plus azacitidine.
Researchers wanted to find out how long participants lived for (overall survival time), after joining the study. Overall survival time was measured as the length of time the participants joined the study until the death of the participant due to any reason. This was measured for each participant and the median number of months participants lived for was calculated for all participants in each group. Median is defined as the middle value of a list of values ordered from smallest to largest. In this analysis, the median survival time was calculated using a statistical model. It uses the ‘already occurred deaths’ and the ‘participants at risk’ to find the survival chance of participants. The participants who took magrolimab plus azacitidine had lesser survival time than participants who took placebo plus azacitidine. Researchers did not see any benefit of magrolimab plus azacitidine treatment in participants with MDS.
For the purpose of this summary, “side effects” are defined as unwanted medical events reported by the participants that the study doctors’ thought might be related to the study treatment.
A side effect is considered “serious” if it:
• results in death
• is life-threatening
• is considered by the study doctor to be medically important • causes lasting problems • requires hospital careThe most common serious side effects were fever with a low number of white blood cells called neutrophils (febrile neutropenia), reaction during or following infusion of a drug (infusion related reaction), and low number of red blood cells (anaemia).
The most common side effects were feeling sick to the stomach (nausea), low number of red blood cells (anaemia), infrequent bowel movements; difficult passage of stools (constipation).
The Sponsor decided to stop the study earlier than planned as the treatment of magrolimab plus azacitidine did not work and there were too many side effects.
REC name
East of England - Essex Research Ethics Committee
REC reference
22/EE/0191
Date of REC Opinion
17 Mar 2021
REC opinion
Further Information Favourable Opinion