Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Gene Therapy Study for Homozygous Familial Hypercholesterolemia (HoFH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02651675
Recruitment Status : Recruiting
First Posted : January 11, 2016
Last Update Posted : September 23, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Regenxbio Inc.

Tracking Information
First Submitted Date  ICMJE January 4, 2016
First Posted Date  ICMJE January 11, 2016
Last Update Posted Date September 23, 2019
Actual Study Start Date  ICMJE March 2016
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 3, 2019)
Number of participants experiencing investigational product-related adverse events [ Time Frame: Up to 24 weeks ]
Physical examinations; Clinical laboratory parameters; and adverse event reporting
Original Primary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
Number of participants experiencing investigational product-related adverse events [ Time Frame: Up to 52 weeks ]
Physical examinations; Clinical laboratory parameters; and adverse event reporting
Change History Complete list of historical versions of study NCT02651675 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2019)
  • Percent change in in LDL-C [ Time Frame: 18 weeks, 12 weeks for cohort 1 only, compared to baseline. ]
    Percent change in LDL-C compared to baseline
  • Percent change in lipid parameters compared to baseline values [ Time Frame: 18 weeks, 12 weeks for cohort 1 only, compared to baseline. ]
    total cholesterol (TC); non-high density lipoprotein cholesterol (non-HDL-C); HDL-C; fasting triglycerides (TG); overflow density lipoprotein cholesterol (VLDL-C); lipoprotein(a) (Lp(a)); apolipoprotein B (apoB) and apolipoprotein A-I (apo A-I)
  • Number of participants experiencing investigational product-related adverse events [ Time Frame: up to 104 weeks ]
    Physical examinations; Clinical laboratory parameters; and adverse event reporting
  • Amount of vector shedding [ Time Frame: up to 104 weeks ]
    Amount of virus secreted in urine and plasma
Original Secondary Outcome Measures  ICMJE
 (submitted: January 7, 2016)
  • Percent change in LDL-C compared to baseline [ Time Frame: 12 weeks ]
  • Percent change in lipid parameters compared to baseline values [ Time Frame: 12 weeks ]
    total cholesterol (TC); non-high density lipoprotein cholesterol (non-HDL-C); HDL-C; fasting triglycerides (TG); overflow density lipoprotein cholesterol (VLDL-C); lipoprotein(a) (Lp(a)); apolipoprotein B (apoB) and apolipoprotein A-I (apo A-I)
  • Fractional catabolic rate (FCR) of LDL apoB [ Time Frame: 12 weeks ]
  • Number of investigational product-related adverse events [ Time Frame: 260 weeks ]
  • Percent change in lipid parameters compared to baseline values [ Time Frame: 260 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Gene Therapy Study for Homozygous Familial Hypercholesterolemia (HoFH)
Official Title  ICMJE AAV8-mediated Low Density Lipoprotein Receptor (LDLR) Gene Replacement in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)
Brief Summary This first-in-human study is intended to evaluate the safety and preliminary effectiveness of AAV-based liver-directed gene therapy in the treatment of adults with Homozygous Familial Hypercholesterolemia (HoFH).
Detailed Description Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by absent or severely reduced capacity to catabolize circulating LDL particles by the hepatic LDL receptor. As a consequence, HoFH subjects present abnormal total plasma cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. Early initiation of aggressive treatment for these patients is therefore essential. Unfortunately, despite existing therapies, treated LDL-C levels could remain well above acceptable levels. Thus, the functional replacement of the defective LDLR via AAV-based liver-directed gene therapy may be a viable approach to treat this disease and improve response to current lipid-lowering treatments. This first-in-human study is intended to evaluate the safety of this gene therapy investigational product and assess preliminary evidence of efficacy using plasma LDL-C levels as a surrogate biomarker for human LDLR transgene expression. Subjects may be asked to participate in an optional kinetics study to assess the metabolic mechanism by which LDL-C is reduced.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Homozygous Familial Hypercholesterolemia (HoFH)
Intervention  ICMJE Biological: AAV directed hLDLR gene therapy
A novel adeno-associated viral (AAV) vector with human low-density lipoprotein receptor (hLDLR) gene
Study Arms  ICMJE Experimental: AAV directed hLDLR gene therapy
Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy
Intervention: Biological: AAV directed hLDLR gene therapy
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: January 7, 2016)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female ≥ 18 years of age.
  • Untreated and/or treated LDL-C levels and clinical presentation consistent with the diagnosis of homozygous FH
  • Molecularly defined LDLR mutations at both LDLR alleles.
  • A baseline serum AAV8 NAb titer ≤ 1:10.

Exclusion Criteria

  • Unwilling to wash out of the following lipid lowering therapies for the pre-specified time period:

    1. niacin > 250 mg/day: within 6 weeks of baseline
    2. fibrates: within 4 weeks of baseline
    3. lomitapide: within 8 weeks of baseline
    4. mipomersen: within 24 weeks of baseline
  • History of cirrhosis or chronic liver disease based on documented histological evaluation or non-invasive imaging or testing.
  • Abnormal liver function tests (LFTs) at screening (AST or ALT > 2 × upper limit of normal (ULN) and/or Total Bilirubin of > 1.5 × ULN
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: Patient Advocacy 1-800-446-3401 HoFH@Regenxbio.com
Listed Location Countries  ICMJE Canada,   Italy,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02651675
Other Study ID Numbers  ICMJE FHGT002
P01HL059407 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Regenxbio Inc.
Study Sponsor  ICMJE Regenxbio Inc.
Collaborators  ICMJE National Heart, Lung, and Blood Institute (NHLBI)
Investigators  ICMJE Not Provided
PRS Account Regenxbio Inc.
Verification Date September 2019

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