Methylmalonic Acidemia (MMA)Phase 1/2reiMMAgineNCT05778877
A Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of SEL-302 in Pediatric Subjects With MMA
A Phase 1/2 study testing SEL-302 in people with Methylmalonic Acidemia (MMA), run by Selecta Biosciences, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 17 years
- Conditions the study is for
- Methylmalonic Acidemia (MMA)
- What is being tested?
- SEL-302
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Dec 2022to Aug 2029
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
- Note: additional inclusion/exclusion criteria may apply, per protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Human Genome Research Institute, National Institutes of Health
Bethesda, Maryland, 20892 - MSC 1646
About this study
Official title: Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of SEL-302 (MMA-101 Following Administration of SEL-110) in Pediatric Subjects With Mut Subtype Isolated Methylmalonic Acidemia (MMA)
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.
Read the detailed description
MMA is a rare inborn error of branched chain amino acid metabolism. Despite strict dietary adherence and vigilant monitoring and care, affected individuals have recurrent episodes of severe illness and develop complications from different organ systems that can be life-threatening. Liver transplants can help, but gene transfer therapy could offer an alternative treatment option. This study will be an open-label, single dose, single center study of SEL-302 consisting of two investigative therapeutics: a gene transfer therapy that is using an inactive virus, called adeno-associated-virus 8 (AAV8), to deliver the MMUT gene to the liver, by itself called MMA-101, and an immunotherapy called SEL-110, a nano-encapsulated form of sirolimus.
The study will enroll two cohorts treating up to a total of 6 subjects.
Cohort 1: 3 adolescents (≥12 and <18 years of age) Cohort 2: 3 children (≥3 and <12 years of age, with a minimum body weight of 15 kg)
The dose of MMA-101 administered to each subject will be 1.0E13 vg/kg. Each progression to the next subject dosed in the study will be reviewed and approved by a data safety monitoring committee.
The first subject in Cohort 1 will receive only MMA-101. The second adolescent subject in Cohort 1 will be treated with 0.15 mg/kg of SEL-110 followed by MMA-101 on Day 1 and two repeat doses of 0.15 mg/kg of SEL-110 at Day 28 and Day 56. The dose of SEL-110 in the third subject in Cohort 1 may be increased up to 0.3 mg/kg depending on results from the second subject. After assessment of safety and efficacy of Cohort 1, Cohort 2 will be started in younger children.
The dose of SEL-110 in Cohort 2 for the first subject will be 0.15 mg/kg of SEL-110 immediately prior to the dose of MMA-101 on Day 1 and two repeat doses of 0.15 mg/kg of SEL-110 at Day 28 and Day 56. The dose of SEL-110 in the second and third subject in Cohort 2 may be increased up to 0.3 mg/kg at one or more of the three doses depending on results of all previously treated subjects.
The primary efficacy endpoints of reduction in serum methylmalonic acid (sMMA) levels and increases in the 1-13C sodium propionate oxidation breath test (POBT) will be assessed at an interim timepoint for safety evaluation (Day 84) and at the primary endpoint of 1 year.
All subjects will be monitored closely for safety for the first year of the study and then annually for an additional 4 years.
- Conditions
- Methylmalonic Acidemia (MMA)
- Being tested
- SEL-302
- Keywords
- MMA, gene therapy, methylmalonic acidemia, adeno associated virus, organic acidemia, Methylmalonyl-CoA Mutase
- Medical subject headings
- Methylmalonic acidemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SEL-302Drug
Also called AAV8-MMUT
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: SEL-302 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From initial treatment with SEL-302 up to 5 years for long-term follow-up.
Secondary outcomes (5)
Maximum plasma concentration (Cmax) of sirolimus
Measuring the Cmax of sirolimus at the first, second, and third dose of SEL-110.
Time Frame: From initial treatment with SEL-302 up to 84 days following administration of SEL-110.
Measured: From initial treatment with SEL-302 up to 84 days following administration of SEL-110.
Area Under Curve (AUC) of sirolimus
Measuring the AUC of sirolimus at the first, second, and third dose of SEL-110.
Measured: 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
Recording of patient outcomes regarding metabolic crisis in need of sick-day dietary modifications, hospitalization, and need for referral for liver, kidney, or liver/kidney transplant.
Measured: 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)
Assess the change from baseline in patient-reported quality of life measures using the WHOQoL-BREF (on a number scale of 0 to 100, with lower indicating a worse outcome).
Measured: From initial treatment with SEL-302 for up to 5 years for long-term follow-up.
Zarit Burden Interview
Assess the change from baseline in patient-reported quality of life measures using the Zarit Burden Interview (on a number scale from 0 to 48, with higher indicating a greater burden)
Measured: From initial treatment with SEL-302 for up to 5 years for long-term follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2023
- Study start19 Dec 2022
- Primary completionAug 2025 (estimated)
- Study completionAug 2029 (estimated)
Why it stopped: Decided by sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Methylmalonic Acidemia (MMA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Selecta Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Human Genome Research Institute (NHGRI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05778877
- Sponsor's protocol ID
- SEL-302.101
- Other IDs
- 000957-HG
- Acronym
- reiMMAgine
- Status last verified
- Sep 2024
- First submitted
- 23 Jan 2023
- Last updated
- 24 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of SEL-302 (MMA-101 Following Administration of SEL-110) in Pediatric Subjects With Mut Subtype Isolated Methylmalonic Acidemia (MMA)
- ClinicalTrials.gov ID
- NCT05778877
- Acronym / sponsor ID
- reiMMAgine / SEL-302.101
- Conditions
- Methylmalonic Acidemia (MMA)
- Keywords
- MMA, gene therapy, methylmalonic acidemia, adeno associated virus, organic acidemia, Methylmalonyl-CoA Mutase
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Decided by sponsor
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Selecta Biosciences, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National Human Genome Research Institute (NHGRI)
- Study start
- 19 Dec 2022 (actual)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Aug 2029 (estimated)
- First posted
- 21 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
MMA is a rare inborn error of branched chain amino acid metabolism. Despite strict dietary adherence and vigilant monitoring and care, affected individuals have recurrent episodes of severe illness and develop complications from different organ systems that can be life-threatening. Liver transplants can help, but gene transfer therapy could offer an alternative treatment option. This study will be an open-label, single dose, single center study of SEL-302 consisting of two investigative therapeutics: a gene transfer therapy that is using an inactive virus, called adeno-associated-virus 8 (AAV8), to deliver the MMUT gene to the liver, by itself called MMA-101, and an immunotherapy called SEL-110, a nano-encapsulated form of sirolimus.
The study will enroll two cohorts treating up to a total of 6 subjects.
Cohort 1: 3 adolescents (≥12 and <18 years of age) Cohort 2: 3 children (≥3 and <12 years of age, with a minimum body weight of 15 kg)
The dose of MMA-101 administered to each subject will be 1.0E13 vg/kg. Each progression to the next subject dosed in the study will be reviewed and approved by a data safety monitoring committee.
The first subject in Cohort 1 will receive only MMA-101. The second adolescent subject in Cohort 1 will be treated with 0.15 mg/kg of SEL-110 followed by MMA-101 on Day 1 and two repeat doses of 0.15 mg/kg of SEL-110 at Day 28 and Day 56. The dose of SEL-110 in the third subject in Cohort 1 may be increased up to 0.3 mg/kg depending on results from the second subject. After assessment of safety and efficacy of Cohort 1, Cohort 2 will be started in younger children.
The dose of SEL-110 in Cohort 2 for the first subject will be 0.15 mg/kg of SEL-110 immediately prior to the dose of MMA-101 on Day 1 and two repeat doses of 0.15 mg/kg of SEL-110 at Day 28 and Day 56. The dose of SEL-110 in the second and third subject in Cohort 2 may be increased up to 0.3 mg/kg at one or more of the three doses depending on results of all previously treated subjects.
The primary efficacy endpoints of reduction in serum methylmalonic acid (sMMA) levels and increases in the 1-13C sodium propionate oxidation breath test (POBT) will be assessed at an interim timepoint for safety evaluation (Day 84) and at the primary endpoint of 1 year.
All subjects will be monitored closely for safety for the first year of the study and then annually for an additional 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - Adolescents | Experimental | Drug: SEL-302IV 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 |
| Cohort 2 - Children | Experimental | Drug: SEL-302IV 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 |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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:
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SEL-302Also: AAV8-MMUTSEL-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 | Drug | Cohort 1 - Adolescents, Cohort 2 - Children |
Primary outcome
Safety and tolerability of SEL-302
Time frame: From the initial administration of SEL-302 up to 5 years for long-term follow-up.
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.
PD Activity of SEL-302
Time frame: From initial treatment with SEL-302 up to 5 years for long-term follow-up.
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.
PD Activity of SEL-302
Time frame: From initial treatment with SEL-302 up to 5 years for long-term follow-up.
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.
Assess the change in Neutralizing antibody (Nab) titers for MMA-101 with treatment of SEL-110
Time frame: From initial treatment with SEL-302 up to 5 years for long-term follow-up.
Measure Nab serum titers from baseline at multiple timepoints following treatment on Day 28, Day 56, and Day 84.
5 secondary outcomes
Maximum plasma concentration (Cmax) of sirolimus
Time frame: From initial treatment with SEL-302 up to 84 days following administration of SEL-110.
Area Under Curve (AUC) of sirolimus
Time frame: 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
Time frame: 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)
Time frame: From initial treatment with SEL-302 for up to 5 years for long-term follow-up.
Zarit Burden Interview
Time frame: From initial treatment with SEL-302 for up to 5 years for long-term follow-up.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SEL-302 in people with Methylmalonic Acidemia (MMA), run by Selecta Biosciences, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of SEL-302 (time frame: From the initial administration of SEL-302 up to 5 years for long-term follow-up.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.