Lysosomal DiseasesPhase 1/2NCT03952637
A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis
A Phase 1/2 study testing AAV9-GLB1, Abdominal ultrasound and Rituximab in people with Lysosomal Diseases and Gangliosidosis, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
Background: GM1 gangliosidosis is a disorder that destroys nerve cells. It is fatal. There is no treatment. People with GM1 are deficient in a certain enzyme. A gene therapy may help the body make this enzyme. This could improve GM1 symptoms. Read more about this study
- Who is it for?
- Ages 6 months to 12 years
- Conditions the study is for
- Lysosomal Diseases, Gangliosidosis, GM1
- What is being tested?
- AAV9-GLB1, Abdominal ultrasound and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2019to 1 Jan 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Type I subjects
- Male or female subjects >= 6 months old and <= 12 months old at time of full ICF signing
- Biallelic mutations in GLB1
- Documented deficiency of Beta-galactosidase enzyme by clinical laboratory testing
- Phenotype consistent with a diagnosis of Type I GM1 gangliosidosis
- Symptomatic subjects: as determined by the opinion of the Principal Investigator and based on the criteria set forth by Brunetti-Pierri et al:
Show all 19Show fewer
- Age of symptom onset <= 6 months of age
- Rapidly progressive with developmental delay and hypotonia
- Pre- symptomatic subjects: must have mutations confirmed to be associated with the Type I subtype
- AAV9 antibody titers <=1:50
- Agree to reside within 50 miles of the study site for at least 1 month following treatment
- Type II subjects
- Vineland-3 Adaptive Behavior composite standard score greater than or equal to 40
- Male or female subjects > 6 months old and < 12 years old at time of full ICF signing
- Biallelic mutations in GLB1
- Documented deficiency of beta-galactosidase enzyme by clinical laboratory testing
- Phenotype consistent with a diagnosis of Type II GM1 gangliosidosis, with symptom onset after the first year of life
- AAV9 antibody titers <=1:50
- Agree to reside within 50 miles of the study site for at least 1 month following treatment
Who cannot join
- AAV9 antibody titers >1:50
- Contraindications to concomitant medications
- Serious illness that would not allow travel to the study site
- Unwilling to undergo study interventions as outlined in the Schedule of Events
- Subjects receiving other unapproved, off-label or experimental therapies for GM1 gangliosidosis (i.e. miglustat, Tanganil) within the last 60 days
- Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered
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- Pregnant or lactating subjects
- Immunizations of any kind in the month prior to screening
- Evidence of cardiomyopathy on history, exam, or additional testing (echocardiogram or electrocardiogram) or other cardiac disease that in the opinion of the investigator would deem the subject unsafe to participate in the trial
- Indwelling ferromagnetic devices that would preclude MRI/fMRI/MRS imaging
- Ongoing medical condition that is deemed by the Principal Investigator to interfere with the conduct or assessments of the study
- History of infection with human immunodeficiency virus (HIV), hepatitis A, B, or C, or tuberculosis.
- History of or current chemotherapy, radiotherapy or other immunosuppressive therapy within the past 30 days. Corticosteroid treatment may be permitted at the discretion of the PI
- Abnormal laboratory values considered clinically significant per the investigator
- Failure to thrive, defined as:
- -- Falling 20 percentiles (20/100) in body weight in the 3 months preceding Screening/Baseline
- Underlying defect in immune function
- History of multiple and severe life-threatening infections
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY8664111010, prpl@cc.nih.gov
About this study
Background:
GM1 gangliosidosis is a disorder that destroys nerve cells. It is fatal. There is no treatment. People with GM1 are deficient in a certain enzyme. A gene therapy may help the body make this enzyme. This could improve GM1 symptoms.
Read more
Objective:
To test if a gene therapy helps Type I and Type II GM1 gangliosidosis symptoms.
Eligibility:
Type I subjects will be male and female >= 6 months <= 12 months of age at the time of full ICF signing.
Type II subjects will be male and female > 12 months old and < 12 years old at the time of full ICF signing.
Design:
Participants will be screened with their medical history and a phone survey.
Participants will stay at NIH for 8-10 weeks.
Participants will have baseline tests:
Blood, urine, and heart tests
Hearing tests
Ultrasound of abdomen
EEG: Sticky patches on the participant s head will measure brain function.
Lumbar puncture: A needle will be stuck into the participant s spine to remove fluid.
MRI scans, bone x-rays, and bone scans: Participants will lie in a machine that takes pictures of the body
IQ tests
Neurology exams
Central line placement
Skin biopsy: A small piece of the participant s skin will be removed.
Speech tests
Participants will have an x-ray while swallowing food.
Participants will take drugs by mouth and IV. This will get their immune system ready for therapy.
Participants will get the gene therapy by IV. They may stay at NIH for a week to watch for side effects.
Participants will have visits 3 and 6 months after treatment. Then visits will be every 6 months for 2 years. Then they will have a visit at 3 years. Visits will take 4-5 days.
Participants will return to NIH once a year for 2 years for tests in an extension study....
Read the detailed description
This is a non-randomized, Phase 1/2 clinical trial to study the safety and efficacy of a single dose gene transfer vector AAV9/GLB1 (AAV9-GLB1) by intravenous infusion to subjects with Type I and Type II GM1 gangliosidosis.
Type I subjects in this study will be male and female, >= 6 months old and <=12 months of age at the time of full ICF signing, with a diagnosis of Type I GM1 gangliosidosis. Type II subjects in this study will be male and female, > 6 months old and < 12 years old at the time of full ICF signing, with a diagnosis of Type II GM1 gangliosidosis. The subjects must have biallelic mutations in GLB1, a deficiency of Beta-galactosidase enzyme documented by testing in a CLIA-certified clinical laboratory, and serum AAV9 antibodies titers <= 1:50). Other inclusion/exclusion criteria apply. In Stage 1, up to 6 Type II subjects will receive 1.5E13 vg/kg of the gene transfer agent, and up to 6 Type II subjects will receive 4.5E13 vg/kg, and up to 6 Type II subjects will recieve 7.5E13 vg/kg of the gene transfer agent. In Stage 1, up to 3 Type I subjects will receive 1.5E13 of the gene transfer agent (Cohort 1) and up to 3 will then receive 4.5E13 of the gene transfer agent (Cohort 2). Dosing will be staggered to ensure subject safety.
Following the last Stage 1 subject s 6 months visit, data will be reviewed, and Stage 2 dosing will be determined. Up to 12 Type II and 6 Type I subjects are planned to be treated in Stage 2 of the study. If Stage 2 dosing is to proceed, it will be reflected in a protocol amendment.
The primary objective of Stage 1 of the study is to assess the safety of the AAV9-GLB1 vector following intravenous infusion. Stage 1 secondary and exploratory objectives include assessment of gene therapy on disease biomarkers, neurologic development and motor function, brain volume and myelination, and immune tolerance to the gene transfer vector.
Stage 2 of the study will assess the safety and efficacy of AAV9-GLB1 vector following intravenous infusion of the dose selected based on data from both Type I and II subjects.
Type I and Type II subjects have differing disease progression and symptomatology, justifying distinct endpoints and timepoint measures.
GM1 gangliosidosis is an autosomal recessive, neurodegenerative lysosomal storage disorder resulting from mutations in the GLB1 gene, encoding the enzyme Beta-galactosidase (Betagal). Betagal functions by removing terminal galactose moieties from GM1 ganglioside, a glycosphingolipid present in highest quantity in the CNS, primarily found in neurons. Betagal deficiency leads to accumulation of GM1 ganglioside and its asialo derivative (GA1) in the CNS. The age of onset and progression of GM1 gangliosidosis differs depending on the amount of residual Betagal activity, but the disease is generally divided into three clinical forms: Type I (infantile), Type IIa and IIb (late-infantile and juvenile), and Type III (adult or chronic). This clinical trial will treat GM1 Type I and Type II subjects.
The Type I form is the most severe, with age of onset less than 12 months of age and death often before age 3. Clinical findings of hypotonia and developmental delay/regression are found in almost all patients. In addition to symptoms resulting from severe CNS degeneration, evidenced by the presence of cherry-red maculae, infants often exhibit peripheral signs, including hepatosplenomegaly, skeletal dysplasia, cardiomyopathy, and coarse facial features.
The Type II form of GM1 generally has onset between 3 and 5 years with plateauing, then regression of developmental milestones (juvenile) or onset of symptoms after 12 months but before 24 months, plateauing of milestones then regression (late infantile).
Clinical features vary but in addition to CNS manifestations typically include a degree of skeletal involvement and mild hepatosplenomegaly. The primary symptoms are frequent falls, poor coordination, dysarthria and cognitive decline. Disease progression is variable, with subjects surviving well into the third decade (juvenile) or into the late teens (late infantile), but with severe cognitive and physical disabilities.
GM1 gangliosidosis is extremely rare, with an incidence estimated at 1:100,000 to 1:200,000. The disease is uniformly fatal with no effective therapy. Care is limited to symptomatic medical management. Intravenous administration of a gene transfer vector to deliver a normal copy of the GLB1 gene to the CNS could potentially provide an effective treatment for GM1 gangliosidosis.
- Conditions
- Lysosomal Diseases, Gangliosidosis, GM1
- Being tested
- AAV9-GLB1, Abdominal ultrasound, Rituximab, Sirolimus, Methylprednisolone
- Keywords
- Lysosomal Diseases
- Medical subject headings
- Gangliosidoses
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV9-GLB1Biological
The risks of administering this treatment in a subject with GM1 gangliosidosis are not completely known. The major risk associated with intravenous infusion is from the subject s immunological response to the viral capsid and/or the beta-gal protein. To reduce this possibility, immune modulation therapy is being started prior to vector delivery and maintained for six months afterward. There is a theoretical risk that the integration of a small percentage of the rAAV vector DNA into the host cell genome could cause cellular transformation to cancer cells and lead to a malignancy. This has never been seen in subjects receiving intravenous AAV9 gene therapy so the risk of this complication, is likely very low.
Abdominal ultrasoundProcedure or surgery
Abdominal ultrasound will be performed as part of screening and safety follow- up studies. The ultrasound will be performed in a radiology department and will take approximately 20-30 minutes.
RituximabDrug
We are proposing the use of immune modulation to transiently deplete B-cells using rituximab. It will be infused at -21 days and -14 days before gene transfer.
SirolimusDrug
Sirolimus is a macrocytic lactone that inhibits T lymphocyte activation and proliferation by inhibiting activation of mammalian Target of Rapamycin (mTOR) kinase that suppresses cytokinedriven T-cell proliferation. We plan to give sirolimus from day -21 to Day 90 with option to extend to day 365 if clinically indicated.
Subjects will receive IV methylprednisolone 1 mg/kg or a maximum dose of 50 mg, 60-120 minutes prior to vector administration on day 0 to mitigate potential acute innate immune response against the vector.
PrednisoneDrug
Prednisone (oral solution, dose 0.5 mg/kg) will be taken daily on Days 1-3.
Audiology assessment with ABRDiagnostic test
The audiology assessment will be performed in the Audiology Clinic using a standard audiogram to measure thresholds for pure tones and speech, word recognition, tympanometry, and otoacoustic emissions if the subject is capable and tolerant of these measures. The assessment will take approximately 30 minutes. The ABR is a noninvasive neurophysiologic test to evaluate electrical signal transmission from the 8th cranial nerve to the brainstem and the cortex in response to specific tones. Electrodes are placed on the scalp and on each earlobe. An earphone gives off a brief click or tone and the electrodes pick up the brain's responses to these sounds and record them. This will be performed by a trained neurophysiology technician to monitor possible change in hearing during treatment. The procedure will be performed in the Interventional Radiology suite while the subject is sedated following the MRI, fMRI, and MRS of the brain.
Bone density scan (DEXA)Diagnostic test
Type II subjects - This is a noninvasive enhanced form of X-ray that is used to measure bone loss. Loss of bone density is a known complication with GM1 gangliosidosis due to decrease in weight-bearing activities with disease progression. The procedure will be performed in the Nuclear Medicine Department. The subject s femur, spine, and whole body will be scanned at baseline and then yearly for 3 years. The procedure will take approximately 10 minutes and may be limited due to the subject s cooperation.
Electrocardiogram (EKG)Diagnostic test
Performed as part of screening and for safety before sedated procedures. The ECG will take approximately 10 minutes and may be limited due to the subject s cooperation.
EchocardiogramDiagnostic test
Performed as part of screening. The Echo will be done in the Echo Lab and may take approximately 20-30 minutes. The exam may be limited due to the subject s cooperation level.
Electroencephalogram (EEG) awake and extended overnightOther
Completed at baseline. The subject will also have an EEG if clinically indicated (for example encephalopathy, seizures, or other change in neurological status or if changes on the previous study are deemed to warrant a follow up study) during post treatment follow up. The procedures will be conducted in the Neurology Testing Department. The total time for an awake EEG, including lead placement, is approximately 40 minutes. An extended overnight EEG will take approximately 12 hours. The exam may be limited due to the subject s cooperation level.
Laboratory testsDiagnostic test
Performed on blood and urine include safety labs, clinically indicated labs and research collections. Additional specimens may be collected for the PI s biorepository or as clinically indicated. Blood volumes for clinical diagnostic testing and research will be consistent with Clinical Center laboratory guidelines.
Lumbar punctureProcedure or surgery
Performed to obtain cerebrospinal fluid (CSF) to measure GM1 ganglioside, beta-gal enzyme, AAV antibodies, Pentasaccharide biomarkers and other research tests. CSF will also be sent for cell count and differential, glucose, protein, and culture as well as CSF neurotransmitters. The amount of CSF obtained will be less than or equal to 0.75 mL/kg body weight. The procedure will be performed while under sedation following MRI imaging. If a sedated MRI is not being performed, then the LP will be performed in consultation with the pediatric consult service using conscious sedation and local anesthesia. The procedure will take approximately 15 minutes.
Brain MRI/MRS/fMRIProcedure or surgery
Magnetic resonance imaging (MRI), functional MRI (fMRI) and spectroscopy (MRS) Procedure/Surgery - The subject will undergo noncontrast MRI, including DTI sequences, fMRI, and MRS in the 3T scanner using the same image acquisition sequences and the same MRS voxels to capture the same metabolites as prior sequencing under natural history protocol 02-HG0107. The MRI, fMRI, and MRS will be interpreted for signs of disease progression or stabilization and any signs of treatment toxicity by two board-certified radiologists with specialty training in neuroradiology. The scan will require anesthesia. Sedation will be administered by the anesthesia service after a preanesthesia consultation to assess risk. The type of sedation and whether the subject will be intubated for the procedure will be at the discretion of the anesthesia service.
Neurocognitive testingBehavioural
Type II Subjects - The Vineland-3 will be administered under the supervision of a psychologist. The Vineland-3 provides several types of scores, measure of personal and social independence designed to examine the domains of communication, daily living skills, social skills and motor development. Other standard neurocognitive instruments may be used depending on the subject s ability, and some visits will (may) include a measure of intelligence /cognitive development if the child is able to achieve a basal score. Neurocognitive testing will take approximately 2-3 hours depending on subject cooperation. The assessments will not address sensitive topics. Type I Subjects - Bayley Scales of Infant and Toddler Development (BSID-III), a well-normed and validated, examiner-administered evaluation of cognition, language, and motor skills for children from birth to 42 months of age.
Neurology examOther
Neurology exam will be performed by a neurologist in the screening and followup appointments to monitor for any adverse reactions and to assess for clinical response to the treatment. The exam will be scripted for consistency within subject visits and between subjects and will take approximately 30 minutes to one hour. The exam will be videotaped. The exam may be limited due to the subject s cooperation level.
PICC or other Central line placementBehavioural
PICC line or other central line placement will be done under sedation in Interventional Radiology. The procedure will be done under sedation and may take 20 minutes. A chest Xray will be done after placement to confirm correct positioning of the catheter.
Skeletal surveyProcedure or surgery
A skeletal survey will be performed to assess the degree of skeletal involvement of the disease. This will include X-rays of the a/p lateral spine, chest, and pelvis. The exam will take approximately 30 minutes. The exam may be limited due to the subject s cooperation level.
Skin biopsyProcedure or surgery
Skin biopsy will be performed on subjects who have not already had a skin biopsy under the 02-HG-0107 protocol. The procedure will be done under sedation using local anesthetic. After washing the skin with chlorhexidine and numbing the skin with injectable lidocaine, a 3mm circle of skin is removed under sterile conditions and the wound is dressed. The entire procedure takes approximately 5 minutes.
Speech and modified barium swallow studyProcedure or surgery
Performed as a marker of response to treatment and safety. The swallow assessments will include a parental swallowing questionnaire and cranial nerve assessment. The NIH Swallowing Questionnaire from the Speech Language Pathology Section is designed to identify the presence and or absence of functional swallowing dysfunction as perceived by the subject and or caregiver. This 4point scale assists with further identification of clinical/research assessments of oral pharyngeal swallowing function if indicated in the form of a modified barium swallow. In addition to swallow assessments, tape recording of speech will also be included with diadochokinetic tasks and sustained phonations as well as speech if able. Recordings will be stored on a shared drive accessible only by the study team. The assessment may take approximately 30 minutes to 1 hour.
Ophthalmology examProcedure or surgery
The ophthalmology exam will be performed by an ophthalmologist in the screening and follow-up appointments to support subtype diagnosis and assess efficacy. Pictures of bilateral macula will be taken and saved to a secure database. OCT will also be performed. These exams will only be administered to Type I subjects.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | In Stage 1, up to 6 Type II subjects will receive 1.5E13 vg/kg of the gene transfer agent, up to 6 Type II subjects will receive 4.5E13 vg/kg, and up to 6 Type II subjects will receive 7.5E13 vg/kg of the gene transfer agent. In Stage 1, up to 3 Type I subjects will receive 1.5E13 of the gene transfer agent (Cohort 1) and up to 3 will then receive 4.5E13 of the gene transfer agent (Cohort 2). Receives: Biological: AAV9-GLB1; Procedure: Abdominal ultrasound; Drug: Rituximab; Drug: Sirolimus; Drug: Methylprednisolone; Drug: Prednisone; Diagnostic Test: Audiology assessment with ABR; Diagnostic Test: Bone density scan (DEXA); Diagnostic Test: Electrocardiogram (EKG); Diagnostic Test: Echocardiogram; Other: Electroencephalogram (EEG) awake and extended overnight; Diagnostic Test: Laboratory tests; Procedure: Lumbar puncture; Procedure: Brain MRI/MRS/fMRI; Behavioral: Neurocognitive testing; Other: Neurology exam; Behavioral: PICC or other Central line placement; Procedure: Skeletal survey; Procedure: Skin biopsy; Procedure: Speech and modified barium swallow study; Procedure: Ophthalmology exam |
| 2 | Experimental | Following the last Stage 1 subject s 6 months visit, data will be reviewed, and Stage 2 dosing and assessments will be determined. If Stage 2 dosing is to proceed, it will be reflected in a protocol amendment. Receives: Biological: AAV9-GLB1; Procedure: Abdominal ultrasound; Drug: Rituximab; Drug: Sirolimus; Drug: Methylprednisolone; Drug: Prednisone; Diagnostic Test: Audiology assessment with ABR; Diagnostic Test: Bone density scan (DEXA); Diagnostic Test: Electrocardiogram (EKG); Diagnostic Test: Echocardiogram; Other: Electroencephalogram (EEG) awake and extended overnight; Diagnostic Test: Laboratory tests; Procedure: Lumbar puncture; Procedure: Brain MRI/MRS/fMRI; Behavioral: Neurocognitive testing; Other: Neurology exam; Behavioral: PICC or other Central line placement; Procedure: Skeletal survey; Procedure: Skin biopsy; Procedure: Speech and modified barium swallow study; Procedure: Ophthalmology exam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Assess the safety of the AAV9/GLB1 vector (AAV9-GLB1) following intravenous delivery.
Measured: Several time points over 3 years
Secondary outcomes (7)
Brain MRI/MRS/fMRI
Type II subjects - Assess brain volume using a 3T MRI, and central nervous system (CNS) metabolite levels by magnetic resonance spectroscopy (MRI) between pre- and post-treatment and compared to historical controls
Measured: Varies between Type II and Type I subjects.
CGI scale
Type II subjects - Assess change in disease severity using the Clinical Global Impressions (CGI) scale.
Measured: Several timepoints over 3 years
Developmental changes
Type II subjects: Assess developmental change in the Growth Scale Scores on the Vineland Adaptive Behavior Scales Third Edition (Vineland-3) instrument between pre- and post-treatment. Type I subjects - Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) Composite score change from baseline
Measured: Varies between Type II and Type I subjects.
Motor function
Type II subjects - Assess motor function using mobility scales developed as part of the natural history study
Measured: Varies between Type II and Type I subjects.
Neurological function
Type I subjects - Neurological functional and developmental change from baseline
Measured: Several timepoints over 3 years
Overall survival
Type I subjects life span is under 5 years
Measured: Throughout study
Diffusion tensor imaging
Change in differential tractography using diffusion tensor imaging (DTI) pre- and post-treatment
Measured: Comparing timepoints throughout the study. Varies between Type II and Type I subjects.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2019
- Study start19 Aug 2019
- Primary completion1 Jan 2030 (estimated)
- Study completion1 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lysosomal DiseasesStudies 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
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Collaborators
- Sio Gene Therapies
- Responsible party
- Sponsor
- Investigators
- Cynthia J Tifft, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03952637
- Sponsor's protocol ID
- 190101
- Other IDs
- 19-HG-0101
- Status last verified
- 17 Sep 2026
- First submitted
- 15 May 2019
- Last updated
- 21 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: pending
Publications
Lewis CJ, D'Souza P, Johnston JM, Acosta MT, Farmer C, Baker EH, Crowell A, Mojica Y, Ashraf S, Joseph L, Vezina G, Quezado Z, Yousef MH, Vardar Z, Shazeeb MS, Corti M, Blackwood M, Coleman K, Batista R, Thurm A, De Boever E, Gahl WA, Byrne BJ, Flotte TR, Jiang X, Gross AL, Keeler AM, Gray-Edwards H, Martin DR, Sena-Esteves M, Tifft CJ. AAV9 Gene Therapy in Type II GM1 Gangliosidosis - A Phase 1-2 Trial. N Engl J Med. 2026 Mar 26;394(12):1184-1194. doi: 10.1056/NEJMoa2510935. Epub 2026 Feb 6.
PubMed 41665410Lewis CJ, D'Souza P, Johnston JM, Acosta MT, Farmer C, Baker EH, Crowell A, Mojica Y, Rahman S, Joseph L, Hartman A, Vezina G, Quezado Z, Yousef MH, Luckett A, Vardar Z, Shazeeb MS, Corti M, Blackwood M, Coleman K, Thurm A, De Boever E, Gahl WA, Byrne BJ, Flotte TR, Jiang X, Gross AL, Keeler AM, Gray-Edwards H, Martin DR, Sena-Esteves M, Tifft CJ. AAV9 Gene Therapy in GM1 Gangliosidosis Type II: A Phase 1/2 Trial. medRxiv [Preprint]. 2025 Jul 29:2025.07.28.25332074. doi: 10.1101/2025.07.28.25332074.
PubMed 40766118Liu S, Ma W, Feng Y, Zhang Y, Jia X, Tang C, Tang F, Wu X, Huang Y. AAV9-coGLB1 Improves Lysosomal Storage and Rescues Central Nervous System Inflammation in a Mutant Mouse Model of GM1 Gangliosidosis. Curr Gene Ther. 2022;22(4):352-365. doi: 10.2174/1566523222666220304092732.
PubMed 35249485
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis
- ClinicalTrials.gov ID
- NCT03952637
- Acronym / sponsor ID
- 190101
- Conditions
- Lysosomal Diseases, Gangliosidosis, GM1
- Keywords
- Lysosomal Diseases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Collaborators
- Sio Gene Therapies
- Study start
- 19 Aug 2019 (actual)
- Primary completion
- 1 Jan 2030 (estimated)
- Study completion
- 1 Jan 2030 (estimated)
- First posted
- 16 May 2019 (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.
Background:
GM1 gangliosidosis is a disorder that destroys nerve cells. It is fatal. There is no treatment. People with GM1 are deficient in a certain enzyme. A gene therapy may help the body make this enzyme. This could improve GM1 symptoms.
Objective:
To test if a gene therapy helps Type I and Type II GM1 gangliosidosis symptoms.
Eligibility:
Type I subjects will be male and female >= 6 months <= 12 months of age at the time of full ICF signing.
Type II subjects will be male and female > 12 months old and < 12 years old at the time of full ICF signing.
Design:
Participants will be screened with their medical history and a phone survey.
Participants will stay at NIH for 8-10 weeks.
Participants will have baseline tests:
Blood, urine, and heart tests
Hearing tests
Ultrasound of abdomen
EEG: Sticky patches on the participant s head will measure brain function.
Lumbar puncture: A needle will be stuck into the participant s spine to remove fluid.
MRI scans, bone x-rays, and bone scans: Participants will lie in a machine that takes pictures of the body
IQ tests
Neurology exams
Central line placement
Skin biopsy: A small piece of the participant s skin will be removed.
Speech tests
Participants will have an x-ray while swallowing food.
Participants will take drugs by mouth and IV. This will get their immune system ready for therapy.
Participants will get the gene therapy by IV. They may stay at NIH for a week to watch for side effects.
Participants will have visits 3 and 6 months after treatment. Then visits will be every 6 months for 2 years. Then they will have a visit at 3 years. Visits will take 4-5 days.
Participants will return to NIH once a year for 2 years for tests in an extension study....
Detailed description
This is a non-randomized, Phase 1/2 clinical trial to study the safety and efficacy of a single dose gene transfer vector AAV9/GLB1 (AAV9-GLB1) by intravenous infusion to subjects with Type I and Type II GM1 gangliosidosis.
Type I subjects in this study will be male and female, >= 6 months old and <=12 months of age at the time of full ICF signing, with a diagnosis of Type I GM1 gangliosidosis. Type II subjects in this study will be male and female, > 6 months old and < 12 years old at the time of full ICF signing, with a diagnosis of Type II GM1 gangliosidosis. The subjects must have biallelic mutations in GLB1, a deficiency of Beta-galactosidase enzyme documented by testing in a CLIA-certified clinical laboratory, and serum AAV9 antibodies titers <= 1:50). Other inclusion/exclusion criteria apply. In Stage 1, up to 6 Type II subjects will receive 1.5E13 vg/kg of the gene transfer agent, and up to 6 Type II subjects will receive 4.5E13 vg/kg, and up to 6 Type II subjects will recieve 7.5E13 vg/kg of the gene transfer agent. In Stage 1, up to 3 Type I subjects will receive 1.5E13 of the gene transfer agent (Cohort 1) and up to 3 will then receive 4.5E13 of the gene transfer agent (Cohort 2). Dosing will be staggered to ensure subject safety.
Following the last Stage 1 subject s 6 months visit, data will be reviewed, and Stage 2 dosing will be determined. Up to 12 Type II and 6 Type I subjects are planned to be treated in Stage 2 of the study. If Stage 2 dosing is to proceed, it will be reflected in a protocol amendment.
The primary objective of Stage 1 of the study is to assess the safety of the AAV9-GLB1 vector following intravenous infusion. Stage 1 secondary and exploratory objectives include assessment of gene therapy on disease biomarkers, neurologic development and motor function, brain volume and myelination, and immune tolerance to the gene transfer vector.
Stage 2 of the study will assess the safety and efficacy of AAV9-GLB1 vector following intravenous infusion of the dose selected based on data from both Type I and II subjects.
Type I and Type II subjects have differing disease progression and symptomatology, justifying distinct endpoints and timepoint measures.
GM1 gangliosidosis is an autosomal recessive, neurodegenerative lysosomal storage disorder resulting from mutations in the GLB1 gene, encoding the enzyme Beta-galactosidase (Betagal). Betagal functions by removing terminal galactose moieties from GM1 ganglioside, a glycosphingolipid present in highest quantity in the CNS, primarily found in neurons. Betagal deficiency leads to accumulation of GM1 ganglioside and its asialo derivative (GA1) in the CNS. The age of onset and progression of GM1 gangliosidosis differs depending on the amount of residual Betagal activity, but the disease is generally divided into three clinical forms: Type I (infantile), Type IIa and IIb (late-infantile and juvenile), and Type III (adult or chronic). This clinical trial will treat GM1 Type I and Type II subjects.
The Type I form is the most severe, with age of onset less than 12 months of age and death often before age 3. Clinical findings of hypotonia and developmental delay/regression are found in almost all patients. In addition to symptoms resulting from severe CNS degeneration, evidenced by the presence of cherry-red maculae, infants often exhibit peripheral signs, including hepatosplenomegaly, skeletal dysplasia, cardiomyopathy, and coarse facial features.
The Type II form of GM1 generally has onset between 3 and 5 years with plateauing, then regression of developmental milestones (juvenile) or onset of symptoms after 12 months but before 24 months, plateauing of milestones then regression (late infantile).
Clinical features vary but in addition to CNS manifestations typically include a degree of skeletal involvement and mild hepatosplenomegaly. The primary symptoms are frequent falls, poor coordination, dysarthria and cognitive decline. Disease progression is variable, with subjects surviving well into the third decade (juvenile) or into the late teens (late infantile), but with severe cognitive and physical disabilities.
GM1 gangliosidosis is extremely rare, with an incidence estimated at 1:100,000 to 1:200,000. The disease is uniformly fatal with no effective therapy. Care is limited to symptomatic medical management. Intravenous administration of a gene transfer vector to deliver a normal copy of the GLB1 gene to the CNS could potentially provide an effective treatment for GM1 gangliosidosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: AAV9-GLB1, Procedure: Abdominal ultrasound, Drug: Rituximab, Drug: Sirolimus, Drug: Methylprednisolone, Drug: Prednisone, Diagnostic Test: Audiology assessment with ABR, Diagnostic Test: Bone density scan (DEXA), Diagnostic Test: Electrocardiogram (EKG), Diagnostic Test: Echocardiogram, Other: Electroencephalogram (EEG) awake and extended overnight, Diagnostic Test: Laboratory tests, Procedure: Lumbar puncture, Procedure: Brain MRI/MRS/fMRI, Behavioral: Neurocognitive testing, Other: Neurology exam, Behavioral: PICC or other Central line placement, Procedure: Skeletal survey, Procedure: Skin biopsy, Procedure: Speech and modified barium swallow study, Procedure: Ophthalmology examIn Stage 1, up to 6 Type II subjects will receive 1.5E13 vg/kg of the gene transfer agent, up to 6 Type II subjects will receive 4.5E13 vg/kg, and up to 6 Type II subjects will receive 7.5E13 vg/kg of the gene transfer agent. In Stage 1, up to 3 Type I subjects will receive 1.5E13 of the gene transfer agent (Cohort 1) and up to 3 will then receive 4.5E13 of the gene transfer agent (Cohort 2). |
| 2 | Experimental | Biological: AAV9-GLB1, Procedure: Abdominal ultrasound, Drug: Rituximab, Drug: Sirolimus, Drug: Methylprednisolone, Drug: Prednisone, Diagnostic Test: Audiology assessment with ABR, Diagnostic Test: Bone density scan (DEXA), Diagnostic Test: Electrocardiogram (EKG), Diagnostic Test: Echocardiogram, Other: Electroencephalogram (EEG) awake and extended overnight, Diagnostic Test: Laboratory tests, Procedure: Lumbar puncture, Procedure: Brain MRI/MRS/fMRI, Behavioral: Neurocognitive testing, Other: Neurology exam, Behavioral: PICC or other Central line placement, Procedure: Skeletal survey, Procedure: Skin biopsy, Procedure: Speech and modified barium swallow study, Procedure: Ophthalmology examFollowing the last Stage 1 subject s 6 months visit, data will be reviewed, and Stage 2 dosing and assessments will be determined. If Stage 2 dosing is to proceed, it will be reflected in a protocol amendment. |
Who may qualify
- Ages
- 6 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (19 listed)
- Type I subjects
- Male or female subjects >= 6 months old and <= 12 months old at time of full ICF signing
- Biallelic mutations in GLB1
- Documented deficiency of Beta-galactosidase enzyme by clinical laboratory testing
- Phenotype consistent with a diagnosis of Type I GM1 gangliosidosis
Key exclusion criteria (18 listed)
- AAV9 antibody titers >1:50
- Contraindications to concomitant medications
- Serious illness that would not allow travel to the study site
- Unwilling to undergo study interventions as outlined in the Schedule of Events
- Subjects receiving other unapproved, off-label or experimental therapies for GM1 gangliosidosis (i.e. miglustat, Tanganil) within the last 60 days
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 |
|---|---|---|
| AAV9-GLB1The risks of administering this treatment in a subject with GM1 gangliosidosis are not completely known. The major risk associated with intravenous infusion is from the subject s immunological response to the viral capsid and/or the beta-gal protein. To reduce this possibility, immune modulation therapy is being started prior to vector delivery and maintained for six months afterward. There is a theoretical risk that the integration of a small percentage of the rAAV vector DNA into the host cell genome could cause cellular transformation to cancer cells and lead to a malignancy. This has never been seen in subjects receiving intravenous AAV9 gene therapy so the risk of this complication, is likely very low. | Biological | 1, 2 |
| Abdominal ultrasoundAbdominal ultrasound will be performed as part of screening and safety follow- up studies. The ultrasound will be performed in a radiology department and will take approximately 20-30 minutes. | Procedure or surgery | 1, 2 |
| RituximabWe are proposing the use of immune modulation to transiently deplete B-cells using rituximab. It will be infused at -21 days and -14 days before gene transfer. | Drug | 1, 2 |
| SirolimusSirolimus is a macrocytic lactone that inhibits T lymphocyte activation and proliferation by inhibiting activation of mammalian Target of Rapamycin (mTOR) kinase that suppresses cytokinedriven T-cell proliferation. We plan to give sirolimus from day -21 to Day 90 with option to extend to day 365 if clinically indicated. | Drug | 1, 2 |
| MethylprednisoloneSubjects will receive IV methylprednisolone 1 mg/kg or a maximum dose of 50 mg, 60-120 minutes prior to vector administration on day 0 to mitigate potential acute innate immune response against the vector. | Drug | 1, 2 |
| PrednisonePrednisone (oral solution, dose 0.5 mg/kg) will be taken daily on Days 1-3. | Drug | 1, 2 |
| Audiology assessment with ABRThe audiology assessment will be performed in the Audiology Clinic using a standard audiogram to measure thresholds for pure tones and speech, word recognition, tympanometry, and otoacoustic emissions if the subject is capable and tolerant of these measures. The assessment will take approximately 30 minutes. The ABR is a noninvasive neurophysiologic test to evaluate electrical signal transmission from the 8th cranial nerve to the brainstem and the cortex in response to specific tones. Electrodes are placed on the scalp and on each earlobe. An earphone gives off a brief click or tone and the electrodes pick up the brain's responses to these sounds and record them. This will be performed by a trained neurophysiology technician to monitor possible change in hearing during treatment. The procedure will be performed in the Interventional Radiology suite while the subject is sedated following the MRI, fMRI, and MRS of the brain. | Diagnostic test | 1, 2 |
| Bone density scan (DEXA)Type II subjects - This is a noninvasive enhanced form of X-ray that is used to measure bone loss. Loss of bone density is a known complication with GM1 gangliosidosis due to decrease in weight-bearing activities with disease progression. The procedure will be performed in the Nuclear Medicine Department. The subject s femur, spine, and whole body will be scanned at baseline and then yearly for 3 years. The procedure will take approximately 10 minutes and may be limited due to the subject s cooperation. | Diagnostic test | 1, 2 |
| Electrocardiogram (EKG)Performed as part of screening and for safety before sedated procedures. The ECG will take approximately 10 minutes and may be limited due to the subject s cooperation. | Diagnostic test | 1, 2 |
| EchocardiogramPerformed as part of screening. The Echo will be done in the Echo Lab and may take approximately 20-30 minutes. The exam may be limited due to the subject s cooperation level. | Diagnostic test | 1, 2 |
| Electroencephalogram (EEG) awake and extended overnightCompleted at baseline. The subject will also have an EEG if clinically indicated (for example encephalopathy, seizures, or other change in neurological status or if changes on the previous study are deemed to warrant a follow up study) during post treatment follow up. The procedures will be conducted in the Neurology Testing Department. The total time for an awake EEG, including lead placement, is approximately 40 minutes. An extended overnight EEG will take approximately 12 hours. The exam may be limited due to the subject s cooperation level. | Other | 1, 2 |
| Laboratory testsPerformed on blood and urine include safety labs, clinically indicated labs and research collections. Additional specimens may be collected for the PI s biorepository or as clinically indicated. Blood volumes for clinical diagnostic testing and research will be consistent with Clinical Center laboratory guidelines. | Diagnostic test | 1, 2 |
| Lumbar puncturePerformed to obtain cerebrospinal fluid (CSF) to measure GM1 ganglioside, beta-gal enzyme, AAV antibodies, Pentasaccharide biomarkers and other research tests. CSF will also be sent for cell count and differential, glucose, protein, and culture as well as CSF neurotransmitters. The amount of CSF obtained will be less than or equal to 0.75 mL/kg body weight. The procedure will be performed while under sedation following MRI imaging. If a sedated MRI is not being performed, then the LP will be performed in consultation with the pediatric consult service using conscious sedation and local anesthesia. The procedure will take approximately 15 minutes. | Procedure or surgery | 1, 2 |
| Brain MRI/MRS/fMRIMagnetic resonance imaging (MRI), functional MRI (fMRI) and spectroscopy (MRS) Procedure/Surgery - The subject will undergo noncontrast MRI, including DTI sequences, fMRI, and MRS in the 3T scanner using the same image acquisition sequences and the same MRS voxels to capture the same metabolites as prior sequencing under natural history protocol 02-HG0107. The MRI, fMRI, and MRS will be interpreted for signs of disease progression or stabilization and any signs of treatment toxicity by two board-certified radiologists with specialty training in neuroradiology. The scan will require anesthesia. Sedation will be administered by the anesthesia service after a preanesthesia consultation to assess risk. The type of sedation and whether the subject will be intubated for the procedure will be at the discretion of the anesthesia service. | Procedure or surgery | 1, 2 |
| Neurocognitive testingType II Subjects - The Vineland-3 will be administered under the supervision of a psychologist. The Vineland-3 provides several types of scores, measure of personal and social independence designed to examine the domains of communication, daily living skills, social skills and motor development. Other standard neurocognitive instruments may be used depending on the subject s ability, and some visits will (may) include a measure of intelligence /cognitive development if the child is able to achieve a basal score. Neurocognitive testing will take approximately 2-3 hours depending on subject cooperation. The assessments will not address sensitive topics. Type I Subjects - Bayley Scales of Infant and Toddler Development (BSID-III), a well-normed and validated, examiner-administered evaluation of cognition, language, and motor skills for children from birth to 42 months of age. | Behavioural | 1, 2 |
| Neurology examNeurology exam will be performed by a neurologist in the screening and followup appointments to monitor for any adverse reactions and to assess for clinical response to the treatment. The exam will be scripted for consistency within subject visits and between subjects and will take approximately 30 minutes to one hour. The exam will be videotaped. The exam may be limited due to the subject s cooperation level. | Other | 1, 2 |
| PICC or other Central line placementPICC line or other central line placement will be done under sedation in Interventional Radiology. The procedure will be done under sedation and may take 20 minutes. A chest Xray will be done after placement to confirm correct positioning of the catheter. | Behavioural | 1, 2 |
| Skeletal surveyA skeletal survey will be performed to assess the degree of skeletal involvement of the disease. This will include X-rays of the a/p lateral spine, chest, and pelvis. The exam will take approximately 30 minutes. The exam may be limited due to the subject s cooperation level. | Procedure or surgery | 1, 2 |
| Skin biopsySkin biopsy will be performed on subjects who have not already had a skin biopsy under the 02-HG-0107 protocol. The procedure will be done under sedation using local anesthetic. After washing the skin with chlorhexidine and numbing the skin with injectable lidocaine, a 3mm circle of skin is removed under sterile conditions and the wound is dressed. The entire procedure takes approximately 5 minutes. | Procedure or surgery | 1, 2 |
| Speech and modified barium swallow studyPerformed as a marker of response to treatment and safety. The swallow assessments will include a parental swallowing questionnaire and cranial nerve assessment. The NIH Swallowing Questionnaire from the Speech Language Pathology Section is designed to identify the presence and or absence of functional swallowing dysfunction as perceived by the subject and or caregiver. This 4point scale assists with further identification of clinical/research assessments of oral pharyngeal swallowing function if indicated in the form of a modified barium swallow. In addition to swallow assessments, tape recording of speech will also be included with diadochokinetic tasks and sustained phonations as well as speech if able. Recordings will be stored on a shared drive accessible only by the study team. The assessment may take approximately 30 minutes to 1 hour. | Procedure or surgery | 1, 2 |
| Ophthalmology examThe ophthalmology exam will be performed by an ophthalmologist in the screening and follow-up appointments to support subtype diagnosis and assess efficacy. Pictures of bilateral macula will be taken and saved to a secure database. OCT will also be performed. These exams will only be administered to Type I subjects. | Procedure or surgery | 1, 2 |
Primary outcome
Safety
Time frame: Several time points over 3 years
Assess the safety of the AAV9/GLB1 vector (AAV9-GLB1) following intravenous delivery.
7 secondary outcomes
Brain MRI/MRS/fMRI
Time frame: Varies between Type II and Type I subjects.
CGI scale
Time frame: Several timepoints over 3 years
Developmental changes
Time frame: Varies between Type II and Type I subjects.
Motor function
Time frame: Varies between Type II and Type I subjects.
Neurological function
Time frame: Several timepoints over 3 years
Overall survival
Time frame: Throughout study
Diffusion tensor imaging
Time frame: Comparing timepoints throughout the study. Varies between Type II and Type I subjects.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Derived from this study: PubMed 41665410Lewis CJ, D'Souza P, Johnston JM, Acosta MT, Farmer C, Baker EH, Crowell A, Mojica Y, Ashraf S, Joseph L, Vezina G, Quezado Z, Yousef MH, Vardar Z, Shazeeb MS, Corti M, Blackwood M, Coleman K, Batista R, Thurm A, De Boever E, Gahl WA, Byrne BJ, Flotte TR, Jiang X, Gross AL, Keeler AM, Gray-Edwards H, Martin DR, Sena-Esteves M, Tifft CJ. AAV9 Gene Therapy in Type II GM1 Gangliosidosis - A Phase 1-2 Trial. N Engl J Med. 2026 Mar 26;394(12):1184-1194. doi: 10.1056/NEJMoa2510935. Epub 2026 Feb 6.
- Derived from this study: PubMed 40766118Lewis CJ, D'Souza P, Johnston JM, Acosta MT, Farmer C, Baker EH, Crowell A, Mojica Y, Rahman S, Joseph L, Hartman A, Vezina G, Quezado Z, Yousef MH, Luckett A, Vardar Z, Shazeeb MS, Corti M, Blackwood M, Coleman K, Thurm A, De Boever E, Gahl WA, Byrne BJ, Flotte TR, Jiang X, Gross AL, Keeler AM, Gray-Edwards H, Martin DR, Sena-Esteves M, Tifft CJ. AAV9 Gene Therapy in GM1 Gangliosidosis Type II: A Phase 1/2 Trial. medRxiv [Preprint]. 2025 Jul 29:2025.07.28.25332074. doi: 10.1101/2025.07.28.25332074.
- Derived from this study: PubMed 35249485Liu S, Ma W, Feng Y, Zhang Y, Jia X, Tang C, Tang F, Wu X, Huang Y. AAV9-coGLB1 Improves Lysosomal Storage and Rescues Central Nervous System Inflammation in a Mutant Mouse Model of GM1 Gangliosidosis. Curr Gene Ther. 2022;22(4):352-365. doi: 10.2174/1566523222666220304092732.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. pending
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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.
Cynthia J Tifft, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
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 AAV9-GLB1, Abdominal ultrasound and Rituximab in people with Lysosomal Diseases and Gangliosidosis, run by National Human Genome Research Institute (NHGRI) 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 19 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 21 Sep 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean M Johnston ((240) 515-1448, johnstonjm@mail.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: Several time points over 3 years). 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 NCT03952637, which also lists 3 linked publications.
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 21 Sep 2026.