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

LogicBio Therapeutics

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Methylmalonic Acidemia

Treatments: Biological: hLB-001

Study type: Interventional

Funder types: Industry

Identifiers

NCT04581785

LB001-001

Details and patient eligibility

About

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.

Enrollment: 4 patients

Sex: All

Ages: 6 months to 12 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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4 participants in 5 patient groups

Dose Level 1 Part A

Experimental group

Description:

3 year-olds to 12 year-olds

Treatment:

Biological: hLB-001

Dose Level 1 Part B

Experimental group

Description:

6 month to 2 year-olds

Treatment:

Biological: hLB-001

Dose Level 1 Part C

Experimental group

Description:

6 month to 12 year-olds

Treatment:

Biological: hLB-001

Dose Level 2 Part A

Experimental group

Description:

3 year-olds to 12 year-olds

Treatment:

Biological: hLB-001

Dose Level 2 Part B

Experimental group

Description:

6 month to 2 year-olds

Treatment:

Biological: hLB-001