Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies (BROADWAY)

NewAmsterdam Pharma

Status and phase: Completed; Phase 3

Conditions: Atherosclerotic Cardiovascular Disease; Dyslipidemias; Hypercholesterolemia; High Cholesterol; Familial Hypercholesterolemia

Treatments: Drug: Placebo; Drug: Obicetrapib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05142722

TA-8995-302

Details and patient eligibility

About

This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with underlying heterozygous familial hypercholesterolemia (HeFH) and/or ASCVD to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy

Full description

This study will be a placebo-controlled, double-blind, randomized, phase 3 study in participants with underlying HeFH and/or ASCVD to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to diet and maximally tolerated lipid-lowering therapy. The screening period for this study will take up to 28 days. Afterwards patients will be randomized to placebo or 10 mg obicetrapib for a 365 day treatment period. After the treatment period, patients will have an end of study follow-up visit.

Enrollment: 2,532 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Females may be enrolled if all 3 of the following criteria are met:
• They are not pregnant;
• They are not breastfeeding; and
• They do not plan on becoming pregnant during the study;
• Have underlying heterozygous familial hypercholesterolemia (HeFH) and/or a history of established ASCVD
• Are on maximally tolerated lipid-modifying therapy as an adjunct to a lipid-lowering diet and other lifestyle modifications, defined as follows:
• A statin at a maximally tolerated stable dose for at least 8 weeks prior to Screening
• Atorvastatin 40 and 80 mg; and
• Rosuvastatin 20 and 40 mg;
• Ezetimibe with or without maximally tolerated statin for at least 8 weeks prior to Screening
• Bempedoic acid with a maximally tolerated statin for at least 8 weeks prior to Screening
• A PCSK-9 targeted therapy alone or in combination with other lipid-modifying therapy for at least 4 stable doses prior to Screening
• Have a fasting serum LDL-C at Screening as follows:
• Fasting serum LDL-C ≥ 55 to < 100 mg/dL (≥1.4 to <2.6 mmol/L) OR non-HDL-C ≥85 mg/dL (≥2.2 mmol/L) to < 130 mg/dL (<3.4 mmol/L) with at least 1 of the following risk enhancers at Screening;
• Recent MI (> 3 and < 12 months prior to Randomization);
• Type 2 diabetes mellitus;
• Current daily cigarette smoking;
• Age of > 60 years;
• High sensitivity C-reactive protein (hsCRP) ≥2.0 mg/L (≥19.0 nmol/L) at Screening or within 6 months prior to Screening
• Fasting triglycerides (TG) > 150 mg/dL (>1.7 mmol/L);
• Fasting lipoprotein (a) > 30 mg/dL (>70 nmol/L); and/or
• Fasting HDL-C < 40 mg/dL (<1.0 mmol/L); OR
• Fasting serum LDL-C ≥ 100 mg/dL (≥2.6 mmol/L) or non-HDL-C ≥130 mg/dL (≥3.4 mmol/L)
• Fasting triglyceride (TG) < 500 mg/dL (<5.7 mmol/L) at Screening; and
• Have an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 at Screening

Exclusion criteria

• New York Heart Association class III or IV heart failure or left ventricular ejection fraction < 30%;
• Hospitalized for heart failure within 5 years prior to Screening
• Major adverse cardiac event (MACE) within 3 months prior to Screening;
• Uncontrolled severe hypertension, defined as either systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg prior to Randomization;
• Formal diagnosis of homozygous familial hypercholesterolemia (HoFH);
• Active liver disease;
• HbA1c ≥10% or a fasting glucose ≥270 mg/dL (≥15.0 mmol/L) at Screening;
• Thyroid-stimulating hormone >1.5 X upper limit of normal (ULN) at Screening;
• Creatine kinase > 3 X upper limit of normal (ULN) at Screening;
• History of malignancy that required surgery (excluding local and wide local excision), radiation therapy, and/or systemic therapy during the 3 years prior to Randomization;
• Known history of alcohol and/or drug abuse within 5 years prior to Randomization
• Received treatment with other investigational products or devices within 30 days of Screening or 5 half-lives of the previous investigational product, whichever is longer;
• Are taking gemfibrozil or have taken gemfibrozil within 30 days of Screening
• Planned use of other investigational products or devices during the course of the study;
• Participated in any clinical trial evaluating obicetrapib; or
• Known allergy or hypersensitivity to obicetrapib, placebo, or any of the excipients in obicetrapib or placebo
• Any condition that, according to the Investigator, could interfere with the conduct of the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,532 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

one placebo tablet once daily

Treatment:

Drug: Placebo

obicetrapib 10mg

Experimental group

Description:

one 10mg obicetrapib tablet once daily

Treatment:

Drug: Obicetrapib