A Placebo-Controlled Phase 3 Study to Evaluate the Effect of 10 mg Obicetrapib in Participants With Atherosclerotic Cardiovascular Disease (ASCVD) Whose Current Treatment with Lipid-Modifying Therapies is not Sufficiently Effective.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

NewAmsterdam Pharma B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

17 May 2022 → ongoing

Decision date (initial)

2023-11-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

NewAmsterdam Pharma BV

External identifiers

EU CT number

2023-507795-51-00

EudraCT number

2021-005092-39

WHO UTN

U1111-1294-3305

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Safety, Efficacy

To evaluate the effect of obicetrapib on the risk of major adverse CV events (MACE), including CV death, non-fatal MI, non-fatal stroke, or non-elective coronary revascularization.

Secondary objectives 5

1. CV death, non-fatal MI, or non-fatal stroke
2. All-cause mortality, non-fatal MI, non-fatal stroke, or non-elective coronary revascularization
3. Total CV events
4. Any individual component of the primary composite endpoint
5. All-cause mortality

Conditions and MedDRA coding

atherosclerotic heart and blood vessel disease (the narrowing of arteries from buildup of plague

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female and ≥18 years of age at Screening (Visit 1)
2. Have a history of ASCVD, defined by at least 1 of the following conditions: Coronary artery disease, Cerebrovascular disease, Peripheral arterial disease
3. Are on maximally tolerated lipid-modifying therapy as an adjunct to a lipid lowering diet and other lifestyle modifications, defined as follows: o A statin at a maximally tolerated stable dose; o Ezetimibe for at least 8 weeks with or without a maximally tolerated statin prior to Screening (Visit 1); o Bempedoic acid for at least 4-8 weeks in combination with a maximally tolerated statin prior to Screening (Visit 1); and/or o A PCSK9-targeted therapy alone or in combination with other lipidmodifying therapy for at least 4 stable doses prior to Screening (Visit 1); o At least 70% of the participants enrolled into this study must be taking HISs. Documentation in the eCRF of the reason why a participant is unable to take HISs is required. HISs include the following: o Atorvastatin 40 and 80 mg; and o Rosuvastatin 20 and 40 mg
4. Have a fasting serum LDL-C at Screening (Visit 1) as follows: o Have a fasting serum LDL-C ≥55 mg/dL to <100 mg/dL with at least 1 of the following risk enhancers: - Recent MI (>3 and <12 months prior to Randomization); - Type 2 diabetes mellitus; - Fasting triglycerides (TG) >150 mg/dL (>1.7 mmol/L); and/or - Fasting high density lipoprotein cholesterol <40 mg/dL (<1.0 mmol/L). OR o Have a fasting serum LDL-C ≥100 mg/dL.
5. Have fasting TG <400 mg/dL (<4.52 mmol/L) at Screening (Visit 1)
6. Have an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration equation at Screening (Visit 1). Other protocol-defined criteria apply.

Exclusion criteria 10

1. Have current or any previous history of New York Heart Association class III or IV HF or left ventricular ejection fraction <30%
2. Have been hospitalized for HF within 5 years prior to Screening (Visit 1)
3. Have had any of the following clinical events within 3 months prior to Screening (Visit 1): o Non-fatal MI; o Non-fatal stroke; o Non-elective coronary revascularization; and/or o Hospitalization for unstable angina and/or chest pain
4. Have uncontrolled severe hypertension, defined as either systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg prior to Randomization, taken as the average of triplicate measurements. One triplicate retest will be allowed during the same visit, at which point if the retest result is no longer exclusionary, the participant may be randomized
5. Have a formal diagnosis of homozygous familial hypercholesterolemia
6. Have active liver disease, defined as any known current infectious, neoplastic, or metabolic pathology of the liver; unexplained elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN); or total bilirubin >2 × ULN at Screening (Visit 1)
7. Have an HbA1c ≥10.0% or a fasting glucose ≥270 mg/dL at Screening (Visit 1);
8. Have a thyroid-stimulating hormone >1.5 × ULN at Screening (Visit 1)
9. Have a creatine kinase >3 × ULN at Screening (Visit 1)
10. Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening (Visit 1)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the time from Randomization to the first confirmed occurrence of any component of the composite endpoint, including the following: - CV death; - Non-fatal MI; - Non-fatal stroke; or - Non-elective coronary revascularization.

Secondary endpoints 5

1. The time from Randomization until the first confirmed occurrence of a composite of CV death, non-fatal MI, or non-fatal stroke
2. The time from Randomization until the first confirmed occurrence of a composite of all-cause mortality, non-fatal MI, non-fatal stroke, or nonelective coronary revascularization
3. A total event analysis, defined as the number of CV death events, and first and subsequent/recurrent events of non-fatal MIs, non-fatal strokes, and non-elective coronary revascularization from Randomization until the EOS Visit
4. The time from Randomization until the first confirmed occurrence of non-fatal MI
5. The time from Randomization until the first confirmed occurrence of non-elective coronary revascularization

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

NewAmsterdam Pharma B.V.

Sponsor organisation

NewAmsterdam Pharma B.V.

Address

Gooimeer 2/35

City

Naarden

Postcode

1411 DC

Country

Netherlands

Scientific contact point

Organisation

NewAmsterdam Pharma B.V.

Contact name

Clinical Operations

Public contact point

Organisation

NewAmsterdam Pharma B.V.

Contact name

Clinical Operations

Third parties 1

Locations

13 EU/EEA countries · 236 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 168 files

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

Application history

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