Double-Blind study comparing venetoclax and azacitidine versus placebo and azacitidine in patients that are newly diagnosed with Higher-Risk Myelodysplastic Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

18 Nov 2020 → ongoing

Decision date (initial)

2023-12-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2023-507153-16-00

EudraCT number

2020-000744-55

ClinicalTrials.gov

NCT04401748

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Efficacy, Safety

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.
The study has reached 100% overall survival (OS) events and completed planned final analysis.

Secondary objectives 3

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.

Conditions and MedDRA coding

Higher-Risk Myelodysplastic Syndrome

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Subjects must be ≥ 18 years of age with a diagnosis of MDS according to the 2016 World Health Organization (WHO) classification with presence of < 20% bone marrow blasts per marrow biopsy/aspirate at screening.
2. Subjects must have no prior therapy for MDS with any hypomethylating agent, chemotherapy, or allogeneic stem cell transplantation, and must meet the following disease activity criteria:  Overall Revised International Prognostic Scoring System (IPSS-R) score > 3 (intermediate, high, or very high);  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2;  Hematopoietic stem cell transplant (HSCT) eligible with no pre-arranged HSCT at the time of Study Day 1 (not to exceed approximately 19% of subjects enrolled on study), or HSCT ineligible without plan for HSCT at the time of Study Day 1.

Exclusion criteria 1

1. For further information on the exclusion criteria, please refer to section 5.1 Eligibility Criteria of the Study Protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is Overall Survival.

Secondary endpoints 7

1. Modified overall response (mOR) defined as complete remission (CR) + partial remission (PR) + marrow CR (mCR)
2. Overall hematological improvement (HI) (platelet, neutrophil, or erythroid)
3. Complete remission
4. Red blood cell (RBC) and platelet transfusion independence for subjects who are transfusion dependent on RBC and/or platelet at baseline
5. Time to deterioration in physical functioning, as measured by the physical functioning domain of EORTC QLQ-C30
6. Change from baseline in fatigue, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue SF 7a
7. Overall response (OR) defined as CR + PR

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinial Trial Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinial Trial Helpdesk

Third parties 5

Locations

9 EU/EEA countries · 55 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 63 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications