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

• ClinicalTrials.gov Identifier: NCT04581785
• Recruitment Status: Active, not recruiting
• First Posted: October 9, 2020
• Last Update Posted: March 1, 2023
• Sponsor: LogicBio Therapeutics, Inc
• Collaborator: Alexion
• Information provided by (Responsible Party): Alexion ( LogicBio Therapeutics, Inc )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Methylmalonic Acidemia	Biological: hLB-001	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 29, 2021
• Estimated Primary Completion Date: December 30, 2023
• Estimated Study Completion Date: December 30, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent adverse events (AEs) [ Time Frame: 52 weeks ]
2. Incidence of infusional toxicities [ Time Frame: 52 weeks ]

Secondary Outcome Measures :

1. Change in serum methylmalonic acid and methylcitrate [ Time Frame: 52 weeks ]
2. Change in serum fibroblast growth factor 21 (FGF21) level [ Time Frame: 52 weeks ]
3. Change in propionate oxidation rate [ Time Frame: 52 weeks ]
4. Change in serum albumin-2A level [ Time Frame: 52 weeks ]
5. Overall Survival: deaths of patients occurring during the study period will be collected [ Time Frame: 52 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Georgia

Clinical Trial Site

Atlanta, Georgia, United States, 30322

United States, Pennsylvania

Clinical Trial Site

Pittsburgh, Pennsylvania, United States, 15224

United States, Tennessee

Clinical Trial Site

Nashville, Tennessee, United States, 37232

United States, Washington

Clinical Trial Site

Seattle, Washington, United States, 98105

Sponsors and Collaborators

LogicBio Therapeutics, Inc

Alexion

More Information

Additional Information:

SUNRISE clinical trial website 

• Responsible Party: LogicBio Therapeutics, Inc
• ClinicalTrials.gov Identifier: NCT04581785
• Other Study ID Numbers: LB001-001
• First Posted: October 9, 2020
• Last Update Posted: March 1, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexion ( LogicBio Therapeutics, Inc ):

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

Additional relevant MeSH terms:

Amino Acid Metabolism, Inborn Errors; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn