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

A Phase 1/2 Open-label Clinical Study of hLB-001 Gene Therapy in Pediatric Patients With Methylmalonic Acidemia Characterized by MMUT Mutations

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.

Study Overview

• Status: Terminated
• Conditions: Methylmalonic Acidemia
• Intervention / Treatment: Biological: hLB-001

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Clinical Trial Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Clinical Trial Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Clinical Trial Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1 Part A; 3 year-olds to 12 year-olds	Biological: hLB-001; hLB-001 via IV infusion
Experimental: Dose Level 1 Part B; 6 month to 2 year-olds	Biological: hLB-001; hLB-001 via IV infusion
Experimental: Dose Level 1 Part C; 6 month to 12 year-olds	Biological: hLB-001; hLB-001 via IV infusion
Experimental: Dose Level 2 Part A; 3 year-olds to 12 year-olds	Biological: hLB-001; hLB-001 via IV infusion
Experimental: Dose Level 2 Part B; 6 month to 2 year-olds	Biological: hLB-001; hLB-001 via IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Below the limit of quantification (BLQ) value was 2.44 nanograms (ng)/milliliter (mL).	Baseline, Week 52

Collaborators and Investigators

• Sponsor: LogicBio Therapeutics, Inc
• Collaborators: Alexion Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2021
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: October 2, 2020
• First Submitted That Met QC Criteria: October 7, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: inborn errors of metabolism; mut0; mut-; mut deficiency; organic acidemia; SUNRISE
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Acid-Base Imbalance; Acidosis; Amino Acid Metabolism, Inborn Errors
• Other Study ID Numbers: LB001-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No