Methylmalonic AcidemiaPhase 1/2SUNRISENCT04581785
Gene Therapy With hLB-001 in Pediatric Patients With Severe Methylmalonic Acidemia
A Phase 1/2 study testing hLB-001 in people with Methylmalonic Acidemia, run by LogicBio Therapeutics, Inc at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 12 years
- Conditions the study is for
- Methylmalonic Acidemia
- What is being tested?
- hLB-001
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 4 sitesUnited States
- Study dates
- 29 May 2021to 10 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 months to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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;
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Clinical Trial Site
Atlanta, Georgia, 30322
Clinical Trial Site
Nashville, Tennessee, 37232
Clinical Trial Site
Pittsburgh, Pennsylvania, 15224
Clinical Trial Site
Seattle, Washington, 98105
About this study
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
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.
- Conditions
- Methylmalonic Acidemia
- Being tested
- hLB-001
- Keywords
- inborn errors of metabolism, mut0, mut-, mut deficiency, organic acidemia, SUNRISE
- Medical subject headings
- Methylmalonic acidemia, Metabolism, Inborn Errors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hLB-001Biological
hLB-001 via IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 Part A | Experimental | 3 year-olds to 12 year-olds Receives: Biological: hLB-001 |
| Dose Level 1 Part B | Experimental | 6 month to 2 year-olds Receives: Biological: hLB-001 |
| Dose Level 1 Part C | Experimental | 6 month to 12 year-olds Receives: Biological: hLB-001 |
| Dose Level 2 Part A | Experimental | 3 year-olds to 12 year-olds Receives: Biological: hLB-001 |
| Dose Level 2 Part B | Experimental | 6 month to 2 year-olds Receives: Biological: hLB-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline up to Week 52
Secondary outcomes (5)
Change From Baseline in Serum Methylmalonic Acid Level at Week 52
Measured: Baseline, Week 52
Change From Baseline in Serum Methylcitrate Level at Week 52
Measured: Baseline, Week 52
Change From Baseline in Serum Fibroblast Growth Factor 21 (FGF21) Level at Week 52
Measured: Baseline, Week 52
Percent Change From Baseline in Propionate Oxidation Rate at Week 52
Measured: 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).
Measured: Baseline, Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start29 May 2021
- Primary completion10 Jan 2023
- Study completion10 Jan 2023
Why it stopped: Due to low likelihood of clinical benefit in treated participants.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Methylmalonic AcidemiaStudies 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- LogicBio Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04581785
- Sponsor's protocol ID
- LB001-001
- Acronym
- SUNRISE
- Status last verified
- Feb 2024
- First submitted
- 2 Oct 2020
- Last updated
- 23 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bedoyan JK, Morgan T, Sun A, Li H, Gruskin D, Payton M, Chereau F, Swenson ES, Lin Q, Kay MA, Vockley J. First-in-human nuclease-free homologous recombination-dependent gene editing in pediatric patients with methylmalonic acidemia: results of a phase 1/2 study. Gene Ther. 2026 May;33(3):345-357. doi: 10.1038/s41434-026-00609-1. Epub 2026 Mar 30.
PubMed 41912673
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04581785
- Acronym / sponsor ID
- SUNRISE / LB001-001
- Conditions
- Methylmalonic Acidemia
- Keywords
- inborn errors of metabolism, mut0, mut-, mut deficiency, organic acidemia, SUNRISE
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to low likelihood of clinical benefit in treated participants.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- LogicBio Therapeutics, IncIndustry (pharma, biotech, devices)
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- 29 May 2021 (actual)
- Primary completion
- 10 Jan 2023 (actual)
- Study completion
- 10 Jan 2023 (actual)
- First posted
- 9 Oct 2020 (actual)
- Results
- Posted 23 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 Part A | Experimental | Biological: hLB-0013 year-olds to 12 year-olds |
| Dose Level 1 Part B | Experimental | Biological: hLB-0016 month to 2 year-olds |
| Dose Level 1 Part C | Experimental | Biological: hLB-0016 month to 12 year-olds |
| Dose Level 2 Part A | Experimental | Biological: hLB-0013 year-olds to 12 year-olds |
| Dose Level 2 Part B | Experimental | Biological: hLB-0016 month to 2 year-olds |
Who may qualify
- Ages
- 6 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| hLB-001hLB-001 via IV infusion | Biological | Dose Level 1 Part A, Dose Level 1 Part B, Dose Level 1 Part C, Dose Level 2 Part A, Dose Level 2 Part B |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to Week 52
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.
Number of Participants With Infusional Toxicities
Time frame: Baseline up to Week 52
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.
5 secondary outcomes
Change From Baseline in Serum Methylmalonic Acid Level at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Serum Methylcitrate Level at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Serum Fibroblast Growth Factor 21 (FGF21) Level at Week 52
Time frame: Baseline, Week 52
Percent Change From Baseline in Propionate Oxidation Rate at Week 52
Time frame: Baseline, Week 52
Change From Baseline in Serum Albumin-2A Level at Week 52
Time frame: Baseline, Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41912673Bedoyan JK, Morgan T, Sun A, Li H, Gruskin D, Payton M, Chereau F, Swenson ES, Lin Q, Kay MA, Vockley J. First-in-human nuclease-free homologous recombination-dependent gene editing in pediatric patients with methylmalonic acidemia: results of a phase 1/2 study. Gene Ther. 2026 May;33(3):345-357. doi: 10.1038/s41434-026-00609-1. Epub 2026 Mar 30.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Methylmalonic Acidemia
RecruitingObservational study
Longitudinal Study of Ultra-rare Inherited Metabolic and Degenerative Neurological Diseases.
Inherited Disease, Rare Diseases
RecruitingObservational study
Clinical and Laboratory Study of Methylmalonic Acidemia
Organic Acidemia, Methylmalonic Acidemia
RecruitingObservational study
A Prospective Study of Pediatric Participants up to 16 Years of Age With Methylmalonic Acidemia (MMA) Due to Mutations in the MMUT Gene
Methylmalonic Acidemia (MMA)
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Active, not recruitingObservational study
Long-term Follow-up Study of Patients Who Received hLB-001 Gene Therapy
Methylmalonic Acidemia
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.
4 sites 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 hLB-001 in people with Methylmalonic Acidemia, run by LogicBio Therapeutics, Inc at 4 sites 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 6 inclusion and 6 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: stopped early, as of the sponsor's last update on 23 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Yes. Results are posted in the registry (first posted 23 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From first dose of study drug up to Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04581785, which also lists 1 linked publication.
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 23 Feb 2024.