A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH
Study Details
Study Description
Brief Summary
AK102 is being developed for the treatment of HoFH. The study will be conducted in 2 parts, part 1 is open label, single arm study to evaluate the safety, tolerability and efficacy of PCSK9 inhibitor AK102, and part 2 is double blind, randomized, placebo controlled study to evaluate the efficacy and safety of PCSK9 inhibitor AK102. The treatment period will last 12 week.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AK102 450mg AK102, Q4W, subcutaneous injection |
Drug: AK102
450mg, Q4W, subcutaneous injection
Drug: Statins
Lipid-lowering therapies
Drug: Ezetimibe
Lipid-lowering therapies
|
| Placebo Comparator: placebo Placebo, Q4W, subcutaneous injection |
Drug: Statins
Lipid-lowering therapies
Drug: Ezetimibe
Lipid-lowering therapies
|
Outcome Measures
Primary Outcome Measures
- Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [Week 12]
- Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1） [From baseline through 12 weeks]
Secondary Outcome Measures
- Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol [From baseline through 12 weeks]
- Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol [From baseline through 12 weeks]
- Percent Change From Baseline in Serum Triglyceride (TG) [From baseline through 12 weeks]
- Percent Change From Baseline in Apolipoprotein B (Apo B) [From baseline through 12 weeks]
- Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) [From baseline through 12 weeks]
- Percent Change From Baseline in Total Cholesterol(TC) [From baseline through 12 weeks]
- Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) [From baseline through 12 weeks]
- Concentrations of AK102 in Serum [Part 1: Day 1,Day 2, Day 4, Day 8, Day 15, Day 22, D29, D57. Part 2: Day 1, Day 29, Day 57]
- Number of subjects who develop detectable anti-drug antibodies (ADAs) [From baseline through 12 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Males and females, ≥18 years of age with a diagnosis of homozygous familial hypercholesterolemia by genetic confirmation or a clinical diagnosis based on a history of an untreated low-density lipoprotein cholesterol (LDL-C) concentration >500 mg/deciliter (dL) [13 millimoles/liter (mmol/L)] together with either xanthoma before 10 years of age or evidence of heterozygous familial hypercholesterolemia in both parents
-
Stable on pre-existing, lipid-lowering therapies (statins in combination with ezetimibe) for at least 4 weeks with no planned medication or dose change for the duration of study participation
-
Fasting central lab LDL-C concentration >130 mg/dL (3.4 mmol/L) and triglyceride concentration <400 mg/dL (4.5 mmol/L).
-
Body weight of 40 kilograms (kg) or greater at screening
Exclusion Criteria:
-
Received LDL plasma replacement therapy within 8 weeks before Investigational product administration
-
Received Lomitapide or Mipomersen within 5 months before Investigational product administration
-
Received prior treatment with PCSK9 inhibitors or AK102.
-
Unexplained creatine kinase (CK) ≥ 5 times the upper limit of normal (ULN)
-
Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 500 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with non-active HBsAg carriers, treated and stable hepatitis B (HBV DNA <500 IU/ mL) , and cured hepatitis C can be enrolled. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative.
-
Known allergic reactions to any ingredients of AK102
-
Any other condition(s) that would compromise the safety of the patient or compromise the quality of the clinical study as judged by the Investigator and/or Medical Monitor.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking Union Medical College Hospital | Beijing | Beijing | China | 100000 |
| 2 | Beijing Anzhen Hospital | Beijing | Beijing | China | 100029 |
Sponsors and Collaborators
- Akeso
- AD Pharmaceuticals Co., Ltd.
Investigators
- Principal Investigator: Shuyang Zhang, MD, Peking Union Medical College Hospital
- Principal Investigator: Lvya Wang, Beijing Anzhen Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AK102-202