A Gene Therapy Study for Homozygous Familial Hypercholesterolemia (HoFH)

NCT02651675 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: FHGT002P01HL059407
• Study Type: interventional
• Target: 9
• Locations: 4 countries
• Sites: 9

Brief Summary

This first-in-human study is intended to evaluate the safety and preliminary effectiveness of AAV (Adeno-associated virus)-based liver-directed gene therapy in the treatment of adults with Homozygous Familial Hypercholesterolemia (HoFH).

Conditions

Homozygous Familial Hypercholesterolemia (HoFH)

Keywords

LDL Receptors; Gene therapy; Metabolic Diseases; Rare diseases; Genetic Diseases; Atherosclerosis; cardiovascular disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With IP (Investigational Product) Related Adverse Events

  Physical examinations; Clinical laboratory parameters; and adverse event reporting

  Up to 24 weeks

Secondary Outcomes (5)

• Percent Change in LDL-C

  18 weeks, 12 weeks for cohort 1 only, compared to baseline

• Percent Change in Lipid Parameters Compared to Baseline Values

  18 weeks, 12 weeks for cohort 1 only, compared to baseline

• Number of Participants With IP Related Adverse Events

  up to 104 weeks

• Amount of Vector Shedding, Urine

  up to 104 weeks

• Amount of Vector Shedding, Plasma

  up to 104 weeks

Study Arms (3)

Cohort 1

EXPERIMENTAL

2.5E12 (genome copies)/kg (kilogram) body weight (E means the exponential constant)

Genetic: AAV directed hLDLR gene therapy

Cohort 2

EXPERIMENTAL

7.5E12 GC/kg body weight

Genetic: AAV directed hLDLR gene therapy

Cohort 2 Expansion

EXPERIMENTAL

7.5E12 GC/kg body weight DSMB (Data Safety Monitoring Board) approved expansion of Dose 2 cohort, 3 additional subjects enrolled and received prophylactic corticosteroids

Genetic: AAV directed hLDLR gene therapy

Interventions

AAV directed hLDLR gene therapy GENETIC

AAV directed hLDLR gene therapy is a novel adeno-associated viral (AAV8) vector with human low-density lipoprotein receptor (hLDLR) gene

Cohort 1; Cohort 2; Cohort 2 Expansion

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Unwilling to wash out of the following lipid lowering therapies for the pre-specified time period:
• niacin \> 250 mg/day: within 6 weeks of baseline
• fibrates: within 4 weeks of baseline
• lomitapide: within 8 weeks of baseline
• 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 (Aspartate aminotransferase) or ALT (Alanine aminotransferase) \> 2 × upper limit of normal (ULN) and/or Total Bilirubin of \> 1.5 × ULN

Sponsors & Collaborators

• REGENXBIO Inc.: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (9)

Boca Raton location

Boca Raton, Florida, 33434, United States

Location

Kansas City Location

Kansas City, Kansas, 66160, United States

Location

Portland location

Portland, Oregon, 97239, United States

Location

Philadelphia Location

Philadelphia, Pennsylvania, 19104, United States

Location

Nashville location

Nashville, Tennessee, 37232, United States

Location

Montreal location

Montreal, Quebec, H1T1C8, Canada

Location

Palermo location

Palermo, PA, 90127, Italy

Location

Rome location

Roma, RM, 00161, Italy

Location

Rotterdam location

Rotterdam, 3015 CE, Netherlands

Location

MeSH Terms

Conditions

Homozygous Familial Hypercholesterolemia; Hyperlipoproteinemia Type II; Metabolic Diseases; Rare Diseases; Genetic Diseases, Inborn; Atherosclerosis; Cardiovascular Diseases

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Limitations and Caveats

Due to early termination of the program for business reasons, planned efficacy analysis was not possible.

Results Point of Contact

• Title: Clinical Development Lead
• Organization: Regenxbio Inc.

srastogi@regenxbio.com

240-552-8968

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: dose escalation

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 11, 2016
• Study Start: March 1, 2016
• Primary Completion: November 27, 2020
• Study Completion: November 27, 2020
• Last Updated: July 13, 2023
• Results First Posted: July 13, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); NL (1); IT (2); CA (1)