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

Methylmalonic Acidemia Clinical Trial

— SUNRISE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04581785
• Other study ID #: LB001-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 29, 2021
• Est. completion date: January 10, 2023

Study information

• Verified date: February 2024
• Source: Alexion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: January 10, 2023
• Est. primary completion date: January 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Acidosis
• Amino Acid Metabolism, Inborn Errors
• Methylmalonic Acidemia

Intervention

Biological:
• hLB-001
hLB-001 via IV infusion

Locations

Country	Name	City	State
United States	Clinical Trial Site	Atlanta	Georgia
United States	Clinical Trial Site	Nashville	Tennessee
United States	Clinical Trial Site	Pittsburgh	Pennsylvania
United States	Clinical Trial Site	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
LogicBio Therapeutics, Inc	Alexion Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAE was an AE that was not present prior to administration of hLB-001, or an event already present that worsened in either severity or frequency following hLB-001administration. A summary of serious adverse events (SAEs) and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.	From first dose of study drug up to Week 52
Primary	Number of Participants With Infusional Toxicities	An infusional toxicity was a hLB-001-related AE that limits, delays, or requires medical intervention during administration. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.	Baseline up to Week 52
Secondary	Change From Baseline in Serum Methylmalonic Acid Level at Week 52		Baseline, Week 52
Secondary	Change From Baseline in Serum Methylcitrate Level at Week 52		Baseline, Week 52
Secondary	Change From Baseline in Serum Fibroblast Growth Factor 21 (FGF21) Level at Week 52		Baseline, Week 52
Secondary	Percent Change From Baseline in Propionate Oxidation Rate at Week 52		Baseline, Week 52
Secondary	Change From Baseline in Serum Albumin-2A Level at Week 52	Below the limit of quantification (BLQ) value was 2.44 nanograms (ng)/milliliter (mL).	Baseline, Week 52

External Links

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