A study to test the effect of BI 456906 on cardiovascular safety in people with overweight or obesity

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A., Boehringer Ingelheim RCV GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

8 Jan 2024 → ongoing

Decision date (initial)

2024-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-502442-27-00

WHO UTN

U1111-1289-0174

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

The primary objective is to demonstrate non-inferiority of survodutide compared with placebo by means of the hazard ratio (survodutide vs. placebo) based on a Cox regression for time to first occurrence of any of the adjudicated components of the primary composite endpoint, defined as CV death, non-fatal stroke, non-fatal myocardial infarction (MI), ischaemia related coronary revascularisation, or heart failure events (HFE) (5P-MACE).

Secondary objectives 5

1. To demonstrate non-inferiority of survodutide compared with placebo by means of the hazard ratio (survodutide vs. placebo) based on a Cox regression for time to first occurrence of any of the adjudicated components of the composite endpoint, defined as CV death, non-fatal stroke, or non-fatal MI (3P-MACE)
2. To demonstrate superiority of survodutide for the difference of adjusted mean for absolute change from baseline in systolic blood pressure (SBP) (mmHg) to Week 72
3. To demonstrate superiority of survodutide for the difference of adjusted mean for absolute change from baseline in waist circumference (reflective of visceral fat, cm) to Week 72
4. To demonstrate superiority survodutide for the difference of adjusted mean for absolute change from baseline to Week 72 in KCCQ-TSS in trial participants with HF at baseline
5. To demonstrate superiority of survodutide compared with placebo by means of the hazard ratio based on a Cox regression for time to first occurrence of any of the adjudicated components of the primary composite endpoint, defined as CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (5P-MACE)

Conditions and MedDRA coding

Obesity

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Pharmaceuticals And Medical Devices Agency, European Medicines Agency, Food And Drug Administration, Center For Drug Evaluation

Plan to share IPD

Yes

IPD plan description

Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed “Document Sharing Agreement”. Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined on the website. Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program. Access Criteria: For study documents – upon signing of a ‚Document Sharing Agreement‘. For study data – 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Male or female, age ≥18 years at the time of signing informed consent, and at least the legal age of consent in countries where it is >18 years
2. BMI ≥27 kg/m2 at screening with either established CVD or with at least 2 weight-related complications or risk factors for CVD, or a combination of both OR BMI ≥30 kg/m2 at screening with either established CVD or CKD, or with at least 2 weight-related complications or risk factors for CVD, or any combination of these
3. Further inclusion criteria apply

Exclusion criteria 5

1. Previous treatment with GLP-1R agonists within 3 months before screening
2. Type 1 diabetes
3. Less than 3 months between the last dose of GLP-1R agonists and GLP-1R agonist/insulin/GIP combinations and screening
4. Known clinically significant gastric emptying abnormality (e.g. severe diabetic gastroparesis or gastric outlet obstruction)
5. Further exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (this includes hospitalisation for heart failure [HHF], emergency room visit, urgent care visit, or urgent outpatient HF visit) (5P-MACE)

Secondary endpoints 27

1. Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, or non-fatal MI (3P-MACE)
2. Absolute change in SBP (mmHg) from baseline to Week 72
3. Absolute change in waist circumference (cm) from baseline to Week 72
4. Absolute change in KCCQ-TSS from baseline to Week 72 in trial participants with HF at baseline
5. Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, ischaemia related coronary revascularisation, or HFE (this includes HHF, emergency room visit, urgent care visit, or urgent outpatient HF visit) (5P-MACE)
6. Percentage change in body weight from baseline to Week 72
7. Absolute change in DBP (mmHg) from baseline to Week 72
8. Absolute change in AST (U/L) from baseline to Week 72
9. Absolute change in ALT (U/L) from baseline to Week 72
10. Absolute change in HbA1c (mmol/mol) from baseline to Week 72 in trial participants with T2DM
11. Absolute change in HbA1c (%) from baseline to Week 72 in trial participants with T2DM
12. Time to onset of T2DM in trial participants without T2DM at baseline
13. Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, or ischaemia related coronary revascularisation (4P-MACE)
14. Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, non-fatal MI, or HFE (3PMACE+ HFE)
15. Time to first occurrence of any of the adjudicated components of the composite endpoint consisting of: CV death, non-fatal stroke, or non-fatal MI (3P-MACE)
16. Time to first occurrence of adjudicated CV death or adjudicated HFE
17. Time to first occurrence of adjudicated CV death or adjudicated HHF
18. Time to first occurrence of adjudicated HFE
19. Time to adjudicated CV death
20. Time to all-cause mortality
21. Time to first occurrence of adjudicated non-fatal MI
22. Time to first occurrence of adjudicated non-fatal stroke
23. Time to first occurrence of adjudicated ischaemia related coronary revascularisation
24. Body weight reduction ≥5% from baseline to Week 72
25. Body weight reduction ≥10% from baseline to Week 72
26. Body weight reduction ≥15% from baseline to Week 72
27. A composite of death, number of adjudicated HFEs (including HHFs, urgent HF visits, and unplanned outpatient visits), time to first adjudicated HFE and change from baseline in KCCQ-TSS at 72 weeks of treatment assessed by the win ratio in trial participants with HF at baseline

Investigational products

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

Test 7

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Third parties 1

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Carrer Prat De La Riba 50, Sant Cugat Del Valles Sant Cugat Del Valles

City

Barcelona

Postcode

08174

Country

Spain

Boehringer Ingelheim RCV GmbH & Co. KG

Sponsor organisation

Boehringer Ingelheim RCV GmbH & Co. KG

Address

Dr.-Boehringer-Gasse 5-11, Meidling Meidling

City

Vienna

Postcode

1121

Country

Austria

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

17 EU/EEA countries · 179 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 539 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