Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia

Study Identifier:
LB001-001
ClinicalTrials.gov Identifier:
NCT04581785
EudraCT Identifier:
N/A
EU CT ID:
N/A
Sponsor:
Alexion Pharmaceuticals
Study Contact Information:
N/A
Recruitment Complete

Study Details

Medical Condition
  • Unmapped
Study Drug
  • Biological: hLB-001
Date
May 2021 - Dec 2023
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 6 Months - 12 Years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • At the time of dosing, patient must be 6 months to 12 years of age
  • Males and females with diagnosis of severe MMA meeting all the following;
  • Isolated MMA with genetically confirmed, pathogenic mutations in the MMUT gene
  • Screening serum/plasma methylmalonic acid level of >100 µmol/L
  • One or more of the following considered by the PI to be MMA-related: (i) An unscheduled ER visit, hospitalization or requirement for sick day diet in the year prior to screening visit (ii) Developmental delay, movement disorder, optic neuropathy or feeding disorder with tube feeding requirement
  • Medically stable for the 2 months prior to the start of screening
Exclusion Criteria
  • Patients with organic acidemias other than isolated MMA, or with any other causes of hyperammonemia
  • Having received MMA-targeted gene therapy or nucleic acid therapy
  • Patients on insulin or high dose hydroxocobalamin (> 1 mg/day OHB12 parenteral)
  • Kidney or liver transplant, including hepatocyte cell therapy
  • Estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 based on age appropriate equations, or ongoing dialysis for renal disease
  • Patient tests positive for anti-rAAV-LK03-neutralizing antibodies
Sex
Female & Male
Age
6 Months - 12 Years

Study Details

Medical Condition
  • Unmapped
Study Drug
  • Biological: hLB-001
Date
May 2021 - Dec 2023
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 6 Months - 12 Years years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • At the time of dosing, patient must be 6 months to 12 years of age
  • Males and females with diagnosis of severe MMA meeting all the following;
  • Isolated MMA with genetically confirmed, pathogenic mutations in the MMUT gene
  • Screening serum/plasma methylmalonic acid level of >100 µmol/L
  • One or more of the following considered by the PI to be MMA-related: (i) An unscheduled ER visit, hospitalization or requirement for sick day diet in the year prior to screening visit (ii) Developmental delay, movement disorder, optic neuropathy or feeding disorder with tube feeding requirement
  • Medically stable for the 2 months prior to the start of screening
Exclusion Criteria
  • Patients with organic acidemias other than isolated MMA, or with any other causes of hyperammonemia
  • Having received MMA-targeted gene therapy or nucleic acid therapy
  • Patients on insulin or high dose hydroxocobalamin (> 1 mg/day OHB12 parenteral)
  • Kidney or liver transplant, including hepatocyte cell therapy
  • Estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 based on age appropriate equations, or ongoing dialysis for renal disease
  • Patient tests positive for anti-rAAV-LK03-neutralizing antibodies

Protocol Summary

The SUNRISE trial is a first-in-human (FIH), open-label, Phase 1/2 clinical trial designed to assess the safety, tolerability and preliminary efficacy of a single intravenous infusion of hLB-001 in pediatric patients with MMA characterized by methylmalonyl-CoA mutase gene (MMUT) mutations. hLB-001 is a liver-targeted, recombinant engineered adeno-associated viral (rAAV) vector utilizing the LK03 capsid (rAAV-LK03), designed to non-disruptively integrate the human methylmalonyl-CoA mutase gene at the albumin locus.

The trial is expected to enroll pediatric patients with ages ranging from 6 months to 12 years, initially starting with 3 to 12 year-old patients and then adding patients aged 6 months to 2 years.

Trial Locations

Location
Status
Location
Clinical Trial Site
Atlanta, Georgia, United States, 30322
Status
N/A
Location
Clinical Trial Site
Pittsburgh, Pennsylvania, United States, 15224
Status
N/A
Location
Clinical Trial Site
Nashville, Tennessee, United States, 37232
Status
N/A
Location
Clinical Trial Site
Seattle, Washington, United States, 98105
Status
N/A