Due to low likelihood of clinical benefit in treated participants.

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.

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

The safety population included all participants who received at least 1 dose of study drug. Cohorts have been combined in the Baseline Characteristics section to maintain participant confidentiality.

From first dose of study drug up to Week 52

The safety population included all participants who received at least 1 dose of study drug.

The study was terminated early due to low likelihood of clinical benefit in treated participants. Hence; no participants were enrolled in Part C and thus Cohort 2 was not initiated.