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

NCT04581785 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: LB001-001
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 4

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.

Conditions

Methylmalonic Acidemia

Keywords

inborn errors of metabolism; mut0; mut-; mut deficiency; organic acidemia; SUNRISE

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• Change From Baseline in Serum Methylmalonic Acid Level at Week 52

  Baseline, Week 52

• Change From Baseline in Serum Methylcitrate Level at Week 52

  Baseline, Week 52

• Change From Baseline in Serum Fibroblast Growth Factor 21 (FGF21) Level at Week 52

  Baseline, Week 52

• Percent Change From Baseline in Propionate Oxidation Rate at Week 52

  Baseline, Week 52

• Change From Baseline in Serum Albumin-2A Level at Week 52

  Baseline, Week 52

Study Arms (5)

Dose Level 1 Part A

EXPERIMENTAL

3 year-olds to 12 year-olds

Biological: hLB-001

Dose Level 1 Part B

EXPERIMENTAL

6 month to 2 year-olds

Biological: hLB-001

Dose Level 1 Part C

EXPERIMENTAL

6 month to 12 year-olds

Biological: hLB-001

Dose Level 2 Part A

EXPERIMENTAL

3 year-olds to 12 year-olds

Biological: hLB-001

Dose Level 2 Part B

EXPERIMENTAL

6 month to 2 year-olds

Biological: hLB-001

Interventions

hLB-001 BIOLOGICAL

hLB-001 via IV infusion

Dose Level 1 Part A; Dose Level 1 Part B; Dose Level 1 Part C; Dose Level 2 Part A; Dose Level 2 Part B

Eligibility Criteria

• Age: 6 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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;
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• LogicBio Therapeutics, Inc: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (4)

Clinical Trial Site

Atlanta, Georgia, 30322, United States

Location

Clinical Trial Site

Pittsburgh, Pennsylvania, 15224, United States

Location

Clinical Trial Site

Nashville, Tennessee, 37232, United States

Location

Clinical Trial Site

Seattle, Washington, 98105, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Methylmalonic acidemia; Metabolism, Inborn Errors

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Alexion Pharmaceuticals Inc.
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials@alexion.com

855-752-2356

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 9, 2020
• Study Start: May 29, 2021
• Primary Completion: January 10, 2023
• Study Completion: January 10, 2023
• Last Updated: February 23, 2024
• Results First Posted: February 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)