Clinical trial NCT04581785: Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia
Official title: A Phase 1/2 Open-label Clinical Study of hLB-001 Gene Therapy in Pediatric Patients With Methylmalonic Acidemia Characterized by MMUT Mutations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Methylmalonic Acidemia
Keywords: inborn errors of metabolism
mut0
mut-
mut deficiency
organic acidemia
SUNRISE
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Alexion Pharmaceuticals, Inc.
First posted: 2020-10-09
Enrollment: 4
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

* At the time of dosing, participants must be 6 months to 12 years of age
* Males and females with diagnosis of severe MMA meeting all the following;

  1. Isolated MMA with genetically confirmed, pathogenic mutations in the MMUT gene
  2. Screening serum/plasma methylmalonic acid level of \>100 µmol/L
  3. 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
  4. Medically stable for the 2 months prior to the start of screening

Exclusion Criteria:

* Participants with organic acidemias other than isolated MMA, or with any other causes of hyperammonemia
* Having received MMA-targeted gene therapy or nucleic acid therapy
* Participants 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
* Participant tests positive for anti-rAAV-LK03-neutralizing antibodies

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug up to Week 52
measure: Number of Participants With Infusional Toxicities
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: Change From Baseline in Serum Methylmalonic Acid Level at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Serum Methylcitrate Level at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Serum Fibroblast Growth Factor 21 (FGF21) Level at Week 52
timeFrame: Baseline, Week 52
measure: Percent Change From Baseline in Propionate Oxidation Rate at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Serum Albumin-2A Level at Week 52
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Clinical Trial Site
state: Georgia
city: Pittsburgh
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Seattle
country: United States
facility: Clinical Trial Site
state: Washington
Study officials:
References: