E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To assess the efficacy of venetoclax in combination with azacitidine compared to placebo with azacitidine in treatment-naïve, higher-risk MDS population.
The hypothesis corresponding to the primary objective is that venetoclax will improve the overall survival (OS) when added to standard of care azacitidine treatment in patients newly diagnosed with higher-risk MDS. |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate various efficacy measures of venetoclax in combination with azacitidine compared to placebo with azacitidine in treatment-naïve, higher-risk MDS population.
2. To evaluate the safety of venetoclax in combination with azacitidine compared to placebo with azacitidine in treatment-naïve, higher-risk MDS population.
3. To evaluate patient-reported outcomes (PROs) for subjects on venetoclax in combination with azacitidine compared to placebo with azacitidine in treatment-naïve, higher-risk MDS population.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult male or female, at least 18 years old. Diagnosis of MDS according to the 2016 WHO classification with presence of < 20% bone marrow blasts per bone marrow biopsy/aspirate at screening. Subject meets the following disease activity criteria: •Overall IPSS-R score > 3 (intermediate, high, or very high; Appendix E); •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; •HSCT eligible with no pre-arranged HSCT at the time of Study Day 1, or HSCT ineligible without plan for HSCT at the time of Study Day 1. No prior therapy for MDS with any hypomethylating agent (for example, azacitidine, decitabine), chemotherapy or allogeneic stem cell transplantation.
For further information on the inclusion criteria, please refer to section 5.1 Eligibility Criteria of the Study Protocol. |
|
E.4 | Principal exclusion criteria |
No previous diagnosis of: •Therapy-related MDS (t-MDS) •MDS evolving from a pre-existing myeloproliferative neoplasm (MPN) •MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN • No prior therapy for MDS with any hypomethylating agent (for example, azacitidine, decitabine), chemotherapy or allogeneic stem cell transplantation. Lenalidomide, anti-thymocyte globulin (ATG), and cyclosporin are also excluded as these are considered disease-modifying agents. • No known active SARS-CoV-2 infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection, they should undergo molecular (e.g., PCR) testing to rule out SARS-CoV-2 infection.
For further information on the exclusion criteria, please refer to section 5.1 Eligibility Criteria of the Study Protocol.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is OS. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Interim analysis of overall survival will occur after approximately 252 overall survival events. Final analysis of overall survival will occur after approximately 336 overall survival events. Survival information will be collected every 8 weeks (+/- 1 week) for up to 5 years after the last subject has been enrolled. |
|
E.5.2 | Secondary end point(s) |
- Modified overall response (mOR) defined as complete remission (CR) + partial remission (PR) + marrow CR (mCR) - Overall hematological improvement (HI) (platelet, neutrophil, or erythroid) - Complete remission - Red blood cell (RBC) and platelet transfusion independence for subjects who are transfusion dependent on RBC and/or platelet at baseline - Time to deterioration in physical functioning, as measured by the physical functioning domain of EORTC QLQ-C30 - Change from baseline in fatigue, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue SF 7a - Overall response (OR) defined as CR + PR |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Brazil |
Canada |
China |
Israel |
Japan |
Korea, Republic of |
Puerto Rico |
Taiwan |
United States |
Russian Federation |
Turkey |
United Kingdom |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Last subject's last visit or date of the last follow-up contact in the last country where the study was conducted, whichever is later. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |