Safety and Efficacy of IBI306 in HeFH Patients

NCT ID: NCT04179669

Last Updated: 2023-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 149 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-20
• Study Completion Date: 2021-06-30

Brief Summary

IBI306 is a fully human monoclonal antibody that binds proprotein convertase substilisin/kexin type 9 (PCSK-9), preventing its interaction with the low-density lipoprotein cholesterol receptor (LDL-R) and thereby restoring LDL-R recycling and low-density lipoprotein cholesterol (LDL-C) uptake. In the phase I study, IBI306 was shown to be safe and well tolerated. There was robust reduction in LDL-C, Apo(B), non-HDL-C and lipoprotein (a) in healthy subjects. This study is a randomized, double-blind, placebo-controlled, repeated-dosing, multiple ascending dose trial to evaluate the efficacy and safety of a novel PCSK-9 anti-body, IBI306, in Chinese patients with heterozygous familial hypercholesterolemia.

Detailed Description

The study plans to enroll 148 patients with heterozygous familial hypercholesterolemia. Subjects will maintain a low-fat diet and stable current lipid-lowering therapy for at least 4 weeks and will be randomized into different dose groups at a 1:1 ratio, followed by a 2:1 randomization double-blind treatment with subcutaneous IBI306 150 mg (n=49) or placebo (n=25) every two weeks; or subcutaneous injection of IBI306 450mg (n=49) or placebo (n=25) every four weeks. Treatment lasts for 12 weeks. After 12 weeks, each group enters a 12-week open-label treatment, in which IBI306 subjects continue to receive IBI306, and placebo subjects shift to receive IBI306. The primary endpoint is the percent change in LDL-C levels relative to baseline at 12 weeks. Secondary endpoints include changes in baseline lipid levels, drug safety, and immunogenicity at 12 weeks and 24 weeks. The exploratory endpoint is the population pharmacokinetic profile of IBI306 in Chinese subjects with heterozygous familial hypercholesterolemia. If necessary, the dose of IBI306 will be adjusted accordingly based on the results of the ongoing multi-dose escalation study. After the open period, the subjects will be given a safety visit for 8 weeks.

Conditions

Heterozygous Familial Hypercholesterolemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

IBI306

Participants received IBI306 150 mg subcutaneously Q2W or 450mg Q4W for 12 weeks.

Group Type: EXPERIMENTAL

IBI306

Intervention Type: DRUG

Administered by subcutaneous injection

placebo

Participants received Placebo 150 mg subcutaneously Q2W or 450mg Q4W for 12 weeks.

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

Administered by subcutaneous injection

Interventions

IBI306

Administered by subcutaneous injection

Intervention Type: DRUG

placebo

Administered by subcutaneous injection

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Provide a signed and dated informed consent form
• Men or women 18 to 70 years of age at screening
• Weight ≥ 40 kg during screening
• Confirmed diagnosis of heterozygous familial hypercholesterolemia
• Maintain a low-fat diet and stabilize the current lipid-lowering therapy

Exclusion Criteria

• Patients diagnosed as homozygous familial hypercholesterolemia
• Dialysis or plasmapheresis performed within 4 months prior to screening
• History of liver transplant
• Subjects adjusted for treatment of statins, ezetimibe, niacin, omega-fatty acids within 4 weeks prior to screening
• New York Heart Association (NYHA) grade III or IV heart failure, or recent detection of left ventricular ejection fraction ≤ 30%
• Have serious cardiovascular, cerebrovascular, liver and kidney related diseases

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innovent Biologics (Suzhou) Co. Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beijing Anzhen Hospital, Capital Medical University

Beijing, , China

Countries

China

References

Chai M, He Y, Zhao W, Han X, Zhao G, Ma X, Qiao P, Shi D, Liu Y, Han W, An P, Li H, Yan S, Ma Q, Deng H, Qian L, Zhou Y; CREDIT-2 investigators. Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2). BMC Med. 2023 Feb 28;21(1):77. doi: 10.1186/s12916-023-02797-8.

Reference Type: DERIVED

PMID: 36855099 (View on PubMed)

Other Identifiers

CIBI306C301

Identifier Type: -

Identifier Source: org_study_id