A Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of SEL-302 in Pediatric Subjects With MMA

NCT05778877 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: SEL-302.101000957-HG
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 1/2 study will evaluate the safety and pharmacodynamics (PD) of SEL-302, which consists of the gene transfer vector MMA-101 following administration of an immunomodulatory SEL-110 agent in pediatric subjects with Methylmalonyl-CoA Mutase (MMUT) MMA.

Conditions

Methylmalonic Acidemia (MMA)

Keywords

MMA; gene therapy; methylmalonic acidemia; adeno associated virus; organic acidemia; Methylmalonyl-CoA Mutase

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability of SEL-302

  Incidence and severity of all adverse events (AEs), treatment emergent AEs (TEAEs), and serious adverse events (SAEs) and their relationship to SEL-302 (MMA-101 or SEL-110) Time Frame: From the initial administration of SEL-302 up to 5 years for long-term follow-up.

  From the initial administration of SEL-302 up to 5 years for long-term follow-up.

• PD Activity of SEL-302

  Measure the change in sMMA levels at Day 84 (interim endpoint for safety assessment) and at the end of the 1-year study period (primary endpoint) and assessed yearly during the 4 years of long-term follow-up.

  From initial treatment with SEL-302 up to 5 years for long-term follow-up.

• PD Activity of SEL-302

  Measure the change in the 1-13C sodium POBT at Day 84 (interim endpoint for safety assessment) and at the end of the 1-year study period (primary endpoint) and assessed yearly during the 4 years of long-term follow-up.

  From initial treatment with SEL-302 up to 5 years for long-term follow-up.

• Assess the change in Neutralizing antibody (Nab) titers for MMA-101 with treatment of SEL-110

  Measure Nab serum titers from baseline at multiple timepoints following treatment on Day 28, Day 56, and Day 84.

  From initial treatment with SEL-302 up to 5 years for long-term follow-up.

Secondary Outcomes (5)

• Maximum plasma concentration (Cmax) of sirolimus

  From initial treatment with SEL-302 up to 84 days following administration of SEL-110.

• Area Under Curve (AUC) of sirolimus

  From initial treatment with SEL-302 up to 84 days following administration of SEL-110.

• Patient outcomes assessed by the frequency and severity of specified clinical events

  From initial treatment with SEL-302 up to 5 years for long-term follow-up.

• World Health Organization Quality of Life Brief Version (WHOQoL-BREF)

  From initial treatment with SEL-302 for up to 5 years for long-term follow-up.

• Zarit Burden Interview

  From initial treatment with SEL-302 for up to 5 years for long-term follow-up.

Study Arms (2)

Cohort 1 - Adolescents

EXPERIMENTAL

IV infusion of MMA-101 in the first patient on Day 1 IV infusion of SEL-302 in the second and third patient on Day 1, followed by two repeat doses of SEL-110 on Day 28 and Day 56 Adolescents ages ≥12 and \<18

Drug: SEL-302

Cohort 2 - Children

EXPERIMENTAL

IV infusion of SEL-302 in all patients on Day 1, followed by two repeat doses of SEL-110 on Day 28 and Day 56 Children ages ≥3 and \<12

Drug: SEL-302

Interventions

SEL-302 DRUG

SEL-302 Drug: MMA-101 (1.0E13 vg/kg) Drug: SEL-110 (0.15 mg/kg or up to 0.3 mg/kg) Other Names: SEL-110.36, ImmTOR

Also known as: AAV8-MMUT

Cohort 1 - Adolescents; Cohort 2 - Children

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 3 to \<18 years at time of consent (assent where possible)
• Confirmed diagnosis of MMUT type methylmalonic acidemia by molecular genetic testing
• Clinical and biochemical diagnosis of severe MMA as defined by:
• sMMA level between 100 to 3,000 μmol/L
• A clinical history consistent with severe MMA
• Subjects must have fully recovered from any hospitalization for metabolic ketoacidosis or surgery at least 4 weeks prior to the start of the screening period.
• Parent or legal guardian are willing and able to provide informed consent. Written assent will be obtained from minors older than age seven whenever possible.
• Subject and caregiver must be willing to comply with study-related assessments and adhere to lifestyle considerations throughout study duration.

You may not qualify if:

• History of any organ transplantation.
• High MMUT liver enzymatic activity in the range seen in healthy subjects or MMA patients after corrective liver transplant, as demonstrated by POBT levels.
• Presence of Nab against AAV8 or polyethylene glycol (PEG)
• An estimated glomerular filtration rate (GFR)\<45 mL/min/1.73 m2 (\<chronic kidney disease stage 3a)
• Hemoglobin \<10 g/dL
• Platelet count \<100,000 per mm3
• History of any malignancy or immunocompromising condition.
• History of anaphylaxis or severe allergic reaction to drug therapy, foods, PEG or polysorbates.
• Previously received gene therapy or messenger ribonucleic acid (mRNA) treatments for MMA.
• Participated in a clinical trial of another (non-gene or mRNA therapy) investigational agent within 30 days prior to screening, or within 5 elimination half-lives of the investigational agent, whichever is longer.

Sponsors & Collaborators

• Selecta Biosciences, Inc.: lead
• National Human Genome Research Institute (NHGRI): collaborator

Study Sites (1)

National Human Genome Research Institute, National Institutes of Health

Bethesda, Maryland, 20892 - MSC 1646, United States

Location

MeSH Terms

Conditions

Methylmalonic acidemia

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: January 23, 2023
• First Posted: March 21, 2023
• Study Start: December 19, 2022
• Primary Completion: August 1, 2025
• Study Completion (Estimated): August 1, 2029
• Last Updated: September 24, 2024

Record last verified: 2024-09

Locations

US (1)