Multiple Ascending Dose Study of PCSK-9 Inhibitor (IBI306) in Chinese Patients With Hypercholesterolemia

NCT03815812 | Completed Phase 2

• 1 other identifier: CIBI306B101
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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 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 safety and tolerability of a novel PCSK-9 anti-body, IBI306, in Chinese patients with hypercholesterolemia.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• AEs/SAEs

  • Percentage of participants with adverse events and severity of adverse events from the first dose to the last visit

  up to 12 weeks

Secondary Outcomes (20)

• Tmax

  up to 12 weeks

• Cmax

  up to 12 weeks

• area under curve (AUC)

  up to 12 weeks

• volume of distribution (Vd)

  up to 12 weeks

• half-life (T1/2)

  up to 12 weeks

Study Arms (2)

IBI306

EXPERIMENTAL

Participants received one of 6 dose levels of IBI306 administered as multiple subcutaneous dose

Drug: IBI306

placebo

PLACEBO COMPARATOR

Participants received matching placebo dose regimen by subcutaneous injection.

Drug: placebo

Interventions

IBI306 DRUG

Cohort 1: 75mg Q2W Cohort 2: 140mg Q2W Cohort 3: 300mg Q4W Cohort 4: 420mg Q4W Cohort 5: 450mg Q6W Cohort 6: 600mg Q6W

IBI306

placebo DRUG

Cohort 1: 75mg Q2W Cohort 2: 140mg Q2W Cohort 3: 300mg Q4W Cohort 4: 420mg Q4W Cohort 5: 450mg Q6W Cohort 6: 600mg Q6W

placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide a signed and dated informed consent form;
• Men or women with an age of 18 to 70 years of age at screening (Inclusive);
• BMI between18kg/m2 and 30kg/m2(Inclusive);
• Diagnosis of hyperlipidemia, and taking statins with moderate doses or above for at least 4 weeks;
• Fasting LDL-C between 100 mg / dl (2.6 mmol / L) and 220 mg / dl (5.7 mmol / L) at screening (Inclusive);
• Fasting triglycerides ≤ 400 mg (4.5 mmol / L) at screening.

You may not qualify if:

• Subject's current statin treatment are stable less than 4 weeks prior to random enrollment
• New York Heart Association (NYHA) III or IV heart failure, or last left ventricular ejection fraction \<30%
• Uncontrolled hypertension, defined as repeated measurements confirmed, sitting systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg.
• Diabetic patients have one of the following conditions;
• Known microvascular and macrovascular complications
• HbA1c\>7.5% within 4 weeks before screening
• Moderate or severe renal insufficiency, defined as the estimated glomerular filtration rate \<60 ml / min / 1.73 m2 during screening (calculated using the MDRD formula)
• Active liver disease or impaired liver function, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the normal upper limit (ULN) at screening.
• Have previously undergone liver transplant surgery.
• Creatine kinase (CK) ≥ 3 times the upper limit of normal (ULN) at screening.
• At the discretion of the investigator, there are known active infections or major blood, kidney, metabolism, gastrointestinal or endocrine dysfunction.
• Female subject of childbearing potential not willing to use an acceptable method(s) of effective birth control during treatment with investigational product and for an additional 15 weeks after the end of treatment with investigational product. Male subjects are reluctant to inform their female sexual partners about their participation in the clinical study.
• Female subject is pregnant or breast feeding, planning to become pregnant or planning to breastfeed during treatment with investigational product and/or within 15 weeks after the end of treatment with investigational product..
• Subjects have been treated with PCSK9 inhibitors or have participated in other PCSK-9 inhibitor studies
• Subject has known sensitivity to the study drug and its excipients

Sponsors & Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.: lead

Study Sites (1)

Peking University First Hospital

Beijing, China

Location

Related Publications (1)

• Cui Y, Zhao X, Qi L, Li X, Huang Z, Yang G, Qian L, Deng H, Li H, Huo Y. A Potential Long-Acting LDL-Cholesterol-Lowering PCSK9 Monoclonal Antibody: Randomized, Placebo-Controlled Phase 1 Studies. JACC Asia. 2021 Nov 9;1(3):411-415. doi: 10.1016/j.jacasi.2021.09.002. eCollection 2021 Dec.

  PMID: 36341216 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Yiming Cui

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

• Huo Yong

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: January 24, 2019
• Study Start: March 7, 2019
• Primary Completion: December 25, 2019
• Study Completion: December 25, 2019
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)