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出境医 / 临床实验 / A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH

A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH

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
Homozygous Familial Hypercholesterolemia Drug: AK102 Drug: Statins Drug: Ezetimibe Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 59 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Study to Evaluate the Safety and Efficacy of PCSK9 Inhibitor AK102 in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
Actual Study Start Date : May 13, 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : June 2021
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 :
  1. Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Week 12 ]
  2. Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1） [ Time Frame: From baseline through 12 weeks ]

Secondary Outcome Measures :
  1. Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol [ Time Frame: From baseline through 12 weeks ]
  2. Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol [ Time Frame: From baseline through 12 weeks ]
  3. Percent Change From Baseline in Serum Triglyceride (TG) [ Time Frame: From baseline through 12 weeks ]
  4. Percent Change From Baseline in Apolipoprotein B (Apo B) [ Time Frame: From baseline through 12 weeks ]
  5. Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) [ Time Frame: From baseline through 12 weeks ]
  6. Percent Change From Baseline in Total Cholesterol(TC) [ Time Frame: From baseline through 12 weeks ]
  7. Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) [ Time Frame: From baseline through 12 weeks ]
  8. Concentrations of AK102 in Serum [ Time Frame: Part 1: Day 1,Day 2, Day 4, Day 8, Day 15, Day 22, D29, D57. Part 2: Day 1, Day 29, Day 57 ]
  9. Number of subjects who develop detectable anti-drug antibodies (ADAs) [ Time Frame: From baseline through 12 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Contacts
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Contact: Xiaoping Jin, PhD +86 (0760) 8987 3999 clinicaltrials@akesobio.com

Locations
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China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100000
Contact: Peipei Chen, MD         
Principal Investigator: Shuyang Zhang, MD         
Beijing Anzhen Hospital Not yet recruiting
Beijing, Beijing, China, 100029
Principal Investigator: Lvya Wang, MD         
Principal Investigator: Yang Lin, PhD         
Sponsors and Collaborators
Akeso
AD Pharmaceuticals Co., Ltd.
Investigators
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Principal Investigator: Shuyang Zhang, MD Peking Union Medical College Hospital
Principal Investigator: Lvya Wang Beijing Anzhen Hospital
Tracking Information
First Submitted Date  ICMJE April 28, 2019
First Posted Date  ICMJE May 1, 2019
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE May 13, 2019
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
  • Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Week 12 ]
  • Incidence of treatment-emergent adverse events as assessed by CTCAE V5.0（only for part 1） [ Time Frame: From baseline through 12 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 30, 2019)
  • Percent Change From Baseline in High-density lipoprotein (HDL) cholesterol [ Time Frame: From baseline through 12 weeks ]
  • Percent Change From Baseline in non High-density lipoprotein (non-HDL) cholesterol [ Time Frame: From baseline through 12 weeks ]
  • Percent Change From Baseline in Serum Triglyceride (TG) [ Time Frame: From baseline through 12 weeks ]
  • Percent Change From Baseline in Apolipoprotein B (Apo B) [ Time Frame: From baseline through 12 weeks ]
  • Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) [ Time Frame: From baseline through 12 weeks ]
  • Percent Change From Baseline in Total Cholesterol(TC) [ Time Frame: From baseline through 12 weeks ]
  • Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) [ Time Frame: From baseline through 12 weeks ]
  • Concentrations of AK102 in Serum [ Time Frame: 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) [ Time Frame: From baseline through 12 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH
Official Title  ICMJE A Phase 2 Study to Evaluate the Safety and Efficacy of PCSK9 Inhibitor AK102 in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Homozygous Familial Hypercholesterolemia
Intervention  ICMJE
  • Drug: AK102
    450mg, Q4W, subcutaneous injection
  • Drug: Statins
    Lipid-lowering therapies
  • Drug: Ezetimibe
    Lipid-lowering therapies
Study Arms  ICMJE
  • Experimental: AK102
    450mg AK102, Q4W, subcutaneous injection
    Interventions:
    • Drug: AK102
    • Drug: Statins
    • Drug: Ezetimibe
  • Placebo Comparator: placebo
    Placebo, Q4W, subcutaneous injection
    Interventions:
    • Drug: Statins
    • Drug: Ezetimibe
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 30, 2019) 		59
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xiaoping Jin, PhD +86 (0760) 8987 3999 clinicaltrials@akesobio.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03933293
Other Study ID Numbers  ICMJE AK102-202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Akeso
Study Sponsor  ICMJE Akeso
Collaborators  ICMJE AD Pharmaceuticals Co., Ltd.
Investigators  ICMJE
Principal Investigator: Shuyang Zhang, MD Peking Union Medical College Hospital
Principal Investigator: Lvya Wang Beijing Anzhen Hospital
PRS Account Akeso
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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