Official Title
A Randomized, Double-blind, Placebo-controlled Phase III Multi-centre Study of Azacitidine With or Without MBG453 for the Treatment of Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R, or Chronic Myelomonocytic Leukemia-2 (CMML-2)
Summary:
This is a Phase III multi-centre, randomized, two-arm parallel-group, double-blind,
placebo-controlled study of MBG453 or placebo added to azacitidine in adult subjects with
intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic
Myelomonocytic Leukemia-2 (CMML-2) who have an indication for treatment with azacitidine in
first-line setting and are not eligible for intensive chemotherapy or hematopoietic stem cell
transplantation (HSCT) according to medical judgment by the investigator.
The purpose of the current study is to assess clinical effects of MBG453 in combination with
azacitidine in adult subjects with IPSS-R intermediate, high, very high risk MDS and CMML-2.
Trial Description
Primary Outcome:
Secondary Outcome:
- Key
secondary endpoint 1: Time to definitive deterioration of fatigue using
Functional Assessment of Cancer Therapy (FACIT)-Fatigue score
- Key secondary endpoint 2: Red Blood Cell transfusion-free intervals
- Key
secondary endpoint: Percent of subjects with at least 3 point confirmed
improvement from baseline in FACIT-fatigue scoresscore
- Key
secondary endpoint 4: Percent of subjects with at least 10 point
confirmed improvement from baseline in physical functioning using
European Or ganization for Research and Treatment of Cancer's Core
Quality of Life Questionnaire (EORTC QLQ-C30)
- Key secondary
endpoint 5: Percent of subjects with at least 10 point confirmed
improvement from baseline in emotional functioning using EORTC-QLQ-C30
- Percentage
of subjects with either CR, or mCR, or PR, or HI in each treatment arm
according to International Working Group for MDS (IWG-MDS) as per
investigator assessment
- Percentage of subjects with SD in each
treatment arm according to International Working Group for MDS (IWG-MDS)
as per investigator assessment
- Progression Free Survival (PFS)
- Leukemia-free survival
- Number
of transfusion dependent subjects at baseline who become Red Blood
Cells/platelets transfusion independent after randomization
- Percentage
of transfusion dependent subjects at baseline who become Red Blood
Cells/platelets transfusion independent after randomization
- Pharmacokinetics of MBG453 (parameter Cmax)
- Pharmacokinetics of MBG453 (parameter AUC)
- Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment
- Change from baseline in the European Quality of Life (EuroQol) - 5 Dimensions, 5 Level Questionnaire (EQ-5D-5L) score over time
- Change
from baseline in the European Quality of Life (EuroQoL) - 5 Dimensions,
5 Level Questionnaire (EQ-5D-5L) Visual Analogue Scale over time
- Change
from baseline to C12D1 of Global Health Status/Quality of Life scores
using European Organization for Research and Treatment of Cancer's Core
Quality of Life Questionnaire (EORTC-QLQ-C30)
This is a Phase III multi-centre, randomized, two-arm parallel-group, double-blind, placebo
controlled study of MBG453 or placebo added to azacitidine in adult subjects with
intermediate, high or very high risk myelodysplastic syndrome (MDS) as per IPSS-R, or Chronic
Myelomonocytic Leukemia-2 (CMML-2).
The primary objective of this study is to compare overall survival (OS) in the MBG453 plus
azacitidine arm versus placebo plus azacitidine arm where OS is the time from randomization
until death due to any cause.
Subjects will be randomized in a 1:1 ratio to treatment arms as follow: MBG453 800 mg IV Q4W
plus azacytidine, Placebo IV Q4W plus azacitidine The randomization will be stratified into 4
groups: intermediate risk MDS, high risk MDS, very high risk MDS and CMML-2.
All subjects who discontinue both study treatments will enter a long-term post-treatment
follow-up including response and PRO assessments, and/or survival follow-up for up to 5 years
after the last subject was randomized.
Subjects will be treated until they experience progression of disease (including
transformation to acute leukemia per WHO 2016 classification), experience unacceptable
toxicity or discontinue the study treatment for other reasons.
Continuation of study treatment beyond progression (excluding transformation to acute
leukemia: continuation in this case is not possible) may be possible in selected subjects.
View this trial on ClinicalTrials.gov