GM1 GangliosidosisPhase 1/2NCT04273269
A Safety and Efficacy Study of LYS-GM101 Gene Therapy in Patients With GM1 Gangliosidosis
A Phase 1/2 study testing LYS-GM101 in people with GM1 Gangliosidosis, run by LYSOGENE at 3 sites in 3 countries.
Trial summary
LYS-GM101 is a gene therapy for GM1 gangliosidosis intended to deliver a functional copy of the GLB1 gene to the central nervous system. This study will assess, in a 2-stage adaptive-design, the safety and efficacy of treatment in subjects with infantile GM1 gangliosidosis. Read more about this study
- Who is it for?
- Ages Up to 3 years
- Conditions the study is for
- GM1 Gangliosidosis
- What is being tested?
- LYS-GM101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 11 May 2021to 22 May 2023
- 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 Up to 3 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Documented GM1 gangliosidosis diagnosis based on genotyping confirming the β-gal gene mutations and/or documented deficiency of β-gal enzyme by laboratory testing
- Children with early infantile GM1 gangliosidosis less than 12 months of age with ability to swallow
- Children with late infantile GM1 gangliosidosis less than 3 years of age with ability to sit
Who cannot join
- Uncontrolled seizure disorder. Patients who are stable on anti-convulsive medications may be included
- More than 40% brain atrophy as measured by MRI total brain volume at screening
- Current participation in a clinical trial of another investigational medicinal product
- Past participation in a gene therapy trial
- History of hematopoietic stem cell transplantation
- Any condition that would contraindicate treatment with immunosuppressant therapy
Show all 13Show fewer
- Presence of concomitant medical condition or anatomical abnormality precluding lumbar puncture or intracisternal injection
- Presence of any permanent items (e.g., metal braces) precluding undergoing MRI
- History of non-GM1 gangliosidosis medical condition that would confound scientific rigor or interpretation of results
- Rare and unrelated serious comorbidities, e.g., Down syndrome, intraventricular hemorrhage in the new-born period, extreme low birth weight (<1500 grams) or known bleeding disorders
- Any vaccination 1 month prior to the planned immunosuppressant treatment
- Serology consistent with HIV exposure or consistent with active hepatitis B or C infection
- Grade 2 or higher lab abnormalities for Liver function tests (LFT), bilirubin, creatinine, hemoglobin, white blood cell (WBC) count, platelet count, prothrombin time (PT), and partial thromboplastin time (PTT), according to CTCAE v5.0
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
United States1 site
Children's Hospital of Orange County (CHOC)
Orange, California, 92868
France1 site
Hôpital Armand-Trousseau, Centre de Référence des Maladies Lysosomales (CRML), Service de Neuropédiatrie
Paris, 75012
United Kingdom1 site
Manchester University NHS Foundation Trust
Manchester, M13 9WL
About this study
Official title: An Open-Label Adaptive-Design Study of Intracisternal Adenoassociated Viral Vector Serotype rh.10 Carrying the Human β-Galactosidase cDNA for Treatment of GM1 Gangliosidosis
LYS-GM101 is a gene therapy for GM1 gangliosidosis intended to deliver a functional copy of the GLB1 gene to the central nervous system. This study will assess, in a 2-stage adaptive-design, the safety and efficacy of treatment in subjects with infantile GM1 gangliosidosis.
Read the detailed description
GM1 gangliosidosis is a fatal autosomal recessive disease caused by mutations in the GLB1 gene leading to accumulation of GM1 ganglioside in neurons and progressive neurodegeneration. There are three pediatric subtypes: early infantile, late infantile and juvenile. This is an interventional, multicenter, single-arm, 2-stage adaptive design study of LYS-GM101 for which the first stage (Stage 1) is for safety evaluation (FIH) and the second stage (Stage 2) will establish efficacy as compared to the natural history of the disease. The participants with infantile GM1 gangliosidosis will receive a single dose of LYS-GM101 by intracisternal injection. After a two-year evaluation period (main part of the study), each participant will be followed for an additional three-year long-term follow-up period.
- Conditions
- GM1 Gangliosidosis
- Being tested
- LYS-GM101
- Keywords
- GM1 Gangliosidosis, Lysosomal Storage Disease, Landing Disease
- Medical subject headings
- Gangliosidosis, GM1, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LYS-GM101Genetic
LYS-GM101 is an adeno-associated viral vector serotype rh.10 (AAVrh.10) carrying the human β-galactosidase gene, formulated as a suspension for injection
| Study group | Role | What they receive |
|---|---|---|
| 8x10^12 vg/Kg LYS-GM101 | Experimental | Subjects will receive a single infusion: 8x10^12 vg/Kg LYS-GM101 Receives: Genetic: LYS-GM101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1: Physical examination by body system
Physical examination by body system: normal/abnormal and change from previous assessment
Measured: Up to 6 months (multiple visits)
Stage 1: Neurological examination
Neurological examination: normal/abnormal motor activity and coordination, and change from previous assessment
Measured: Up to 6 months (multiple visits)
Stage 1: Vital signs: change from baseline in heart rate
Vital signs: change from baseline in heart rate
Measured: Up to 6 months (multiple visits)
Stage 1: Vital signs: change from baseline in body temperature
Vital signs: change from baseline in body temperature
Measured: Up to 6 months (multiple visits)
Stage 1: Vital signs: change from baseline in diastolic and systolic blood pressure
Vital signs: change from baseline in diastolic and systolic blood pressure
Measured: Up to 6 months (multiple visits)
Stage 1: Imaging: presence of bleeding post-administration
Imaging: presence of bleeding post-administration
Measured: Up to 6 months (multiple visits)
Stage 1: Change from baseline in biochemistry laboratory parameters
Change from baseline in biochemistry laboratory parameters
Measured: Up to 6 months (multiple visits)
Stage 1: Change from baseline in coagulation and hematology laboratory parameters
Change from baseline in coagulation and hematology laboratory parameters
Measured: Up to 6 months (multiple visits)
Stage 1: Incidence of treatment-emergent adverse event and serious adverse events
Incidence of treatment-emergent adverse event and serious adverse events
Measured: Up to 6 months (multiple visits)
Stage 1: Assessment of humoral immune response by measurement of antibodies anti-AAV and anti-beta-galactosidase (ELISA) and cellular immune response by beta-galactosidase-specific T-cell proliferation assay
Assessment of humoral immune response by measurement of antibodies anti-AAV and anti-beta-galactosidase (ELISA) and cellular immune response by beta-galactosidase-specific T-cell proliferation assay
Measured: Up to 6 months (multiple visits)
Secondary outcomes (6)
Motor Function
Assess change from baseline in motor function using the Hammersmith Infant Neurological Evaluation (HINE) or Hammersmith Functional Motor Scale-Expanded (HFMSE) instruments
Measured: Up to 2 years (multiple visits)
Brain MRI
Assess brain atrophy and brain volume
Measured: Up to 2 years (multiple visits)
Developmental changes (VABS-II)
Assess developmental change from baseline in the Vineland Adaptive Behavior Scale-II-Expanded Interview (VABS-II) instrument
Measured: Up to 2 years (multiple visits)
Developmental changes (BSID-III or KABC-II)
Assess developmental change from baseline in the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) or the Kaufman Assessment Battery for Children, 2nd Edition (KABC-II) instruments
Measured: Up to 2 years (multiple visits)
Blood and cerebrospinal fluid (CSF) biomarkers (beta-galactosidase)
Assess change in beta-galactosidase activity measured from baseline
Measured: Up to 2 years (multiple visits)
Blood and cerebrospinal fluid (CSF) biomarkers (GM1 ganglioside)
Assess change in GM1 ganglioside level measured from baseline
Measured: Up to 2 years (multiple visits)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2020
- Study start11 May 2021
- Primary completion22 May 2023
- Study completion22 May 2023
Why it stopped: The clinical trial is closed due to Lysogene's cessation of activities. This study closure is not due to safety reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GM1 GangliosidosisStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- LYSOGENE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Operations, Study director, LYSOGENE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04273269
- Sponsor's protocol ID
- P1-GM-101
- Status last verified
- Jun 2023
- First submitted
- 21 Jan 2020
- Last updated
- 9 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum Gene Ther. 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067.
PubMed 37624739
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Adaptive-Design Study of Intracisternal Adenoassociated Viral Vector Serotype rh.10 Carrying the Human β-Galactosidase cDNA for Treatment of GM1 Gangliosidosis
- ClinicalTrials.gov ID
- NCT04273269
- Acronym / sponsor ID
- P1-GM-101
- Conditions
- GM1 Gangliosidosis
- Keywords
- GM1 Gangliosidosis, Lysosomal Storage Disease, Landing Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The clinical trial is closed due to Lysogene's cessation of activities. This study closure is not due to safety reasons.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- LYSOGENEIndustry (pharma, biotech, devices)
- Study start
- 11 May 2021 (actual)
- Primary completion
- 22 May 2023 (actual)
- Study completion
- 22 May 2023 (actual)
- First posted
- 18 Feb 2020 (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.
LYS-GM101 is a gene therapy for GM1 gangliosidosis intended to deliver a functional copy of the GLB1 gene to the central nervous system. This study will assess, in a 2-stage adaptive-design, the safety and efficacy of treatment in subjects with infantile GM1 gangliosidosis.
Detailed description
GM1 gangliosidosis is a fatal autosomal recessive disease caused by mutations in the GLB1 gene leading to accumulation of GM1 ganglioside in neurons and progressive neurodegeneration. There are three pediatric subtypes: early infantile, late infantile and juvenile. This is an interventional, multicenter, single-arm, 2-stage adaptive design study of LYS-GM101 for which the first stage (Stage 1) is for safety evaluation (FIH) and the second stage (Stage 2) will establish efficacy as compared to the natural history of the disease. The participants with infantile GM1 gangliosidosis will receive a single dose of LYS-GM101 by intracisternal injection. After a two-year evaluation period (main part of the study), each participant will be followed for an additional three-year long-term follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 8x10^12 vg/Kg LYS-GM101 | Experimental | Genetic: LYS-GM101Subjects will receive a single infusion: 8x10^12 vg/Kg LYS-GM101 |
Who may qualify
- Ages
- Up to 3 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Documented GM1 gangliosidosis diagnosis based on genotyping confirming the β-gal gene mutations and/or documented deficiency of β-gal enzyme by laboratory testing
- Children with early infantile GM1 gangliosidosis less than 12 months of age with ability to swallow
- Children with late infantile GM1 gangliosidosis less than 3 years of age with ability to sit
Key exclusion criteria (13 listed)
- Uncontrolled seizure disorder. Patients who are stable on anti-convulsive medications may be included
- More than 40% brain atrophy as measured by MRI total brain volume at screening
- Current participation in a clinical trial of another investigational medicinal product
- Past participation in a gene therapy trial
- History of hematopoietic stem cell transplantation
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 |
|---|---|---|
| LYS-GM101LYS-GM101 is an adeno-associated viral vector serotype rh.10 (AAVrh.10) carrying the human β-galactosidase gene, formulated as a suspension for injection | Genetic | 8x10^12 vg/Kg LYS-GM101 |
Primary outcome
Stage 1: Physical examination by body system
Time frame: Up to 6 months (multiple visits)
Physical examination by body system: normal/abnormal and change from previous assessment
Stage 1: Neurological examination
Time frame: Up to 6 months (multiple visits)
Neurological examination: normal/abnormal motor activity and coordination, and change from previous assessment
Stage 1: Vital signs: change from baseline in heart rate
Time frame: Up to 6 months (multiple visits)
Vital signs: change from baseline in heart rate
Stage 1: Vital signs: change from baseline in body temperature
Time frame: Up to 6 months (multiple visits)
Vital signs: change from baseline in body temperature
Stage 1: Vital signs: change from baseline in diastolic and systolic blood pressure
Time frame: Up to 6 months (multiple visits)
Vital signs: change from baseline in diastolic and systolic blood pressure
Stage 1: Imaging: presence of bleeding post-administration
Time frame: Up to 6 months (multiple visits)
Imaging: presence of bleeding post-administration
Stage 1: Change from baseline in biochemistry laboratory parameters
Time frame: Up to 6 months (multiple visits)
Change from baseline in biochemistry laboratory parameters
Stage 1: Change from baseline in coagulation and hematology laboratory parameters
Time frame: Up to 6 months (multiple visits)
Change from baseline in coagulation and hematology laboratory parameters
Stage 1: Incidence of treatment-emergent adverse event and serious adverse events
Time frame: Up to 6 months (multiple visits)
Incidence of treatment-emergent adverse event and serious adverse events
Stage 1: Assessment of humoral immune response by measurement of antibodies anti-AAV and anti-beta-galactosidase (ELISA) and cellular immune response by beta-galactosidase-specific T-cell proliferation assay
Time frame: Up to 6 months (multiple visits)
Assessment of humoral immune response by measurement of antibodies anti-AAV and anti-beta-galactosidase (ELISA) and cellular immune response by beta-galactosidase-specific T-cell proliferation assay
6 secondary outcomes
Motor Function
Time frame: Up to 2 years (multiple visits)
Brain MRI
Time frame: Up to 2 years (multiple visits)
Developmental changes (VABS-II)
Time frame: Up to 2 years (multiple visits)
Developmental changes (BSID-III or KABC-II)
Time frame: Up to 2 years (multiple visits)
Blood and cerebrospinal fluid (CSF) biomarkers (beta-galactosidase)
Time frame: Up to 2 years (multiple visits)
Blood and cerebrospinal fluid (CSF) biomarkers (GM1 ganglioside)
Time frame: Up to 2 years (multiple visits)
Results and safety
The study was stopped early (reason given: The clinical trial is closed due to Lysogene's cessation of activities. This study closure is not due to safety reasons.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Derived from this study: PubMed 37624739De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum Gene Ther. 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067.
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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.
Clinical Operations study director
LYSOGENE
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing LYS-GM101 in people with GM1 Gangliosidosis, run by LYSOGENE at 3 sites in 3 countries.
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 3 inclusion and 13 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 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, France, United Kingdom. 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 stopped early (reason given: The clinical trial is closed due to Lysogene's cessation of activities. This study closure is not due to safety reasons.). Results are not available in the source record.
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?
Stage 1: Physical examination by body system (time frame: Up to 6 months (multiple visits)). The study lists 10 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 NCT04273269, 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 9 Jun 2023.