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

Sponsor

LogicBio Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04581785

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Anticipated 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

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

Dec 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

Incidence of treatment-emergent adverse events (AEs) [52 weeks]
Incidence of infusional toxicities [52 weeks]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

At the time of dosing, patient 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

Exclusion Criteria:

Patients with organic acidemias other than isolated MMA, or with any other causes of hyperammonemia
Having received MMA-targeted gene therapy or nucleic acid therapy
Patients 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
Patient tests positive for anti-rAAV-LK03-neutralizing antibodies

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University	Atlanta	Georgia	United States	30322
2	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
3	Vanderbilt Children's Hospital	Nashville	Tennessee	United States	37232
4	Seattle Children's Hospital	Seattle	Washington	United States	98105