RECRUITING

Safety and Efficacy of GS-100 Gene Therapy in Patients With NGLY1 Deficiency

Conditions

NGLY1 Deficiency Gene Therapy Intervention study Infusions, Intraventricular Biomarker Enzyme Replacement Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

A non-randomized, open-label, dose escalation study of a single intracerebroventricular (ICV) administration of a gene replacement therapy in subjects who are 2 to 18 years old with NGLY1 Deficiency.

Official Title

A Phase 1/2/3 Open-label, Single Arm, Dose-finding Study to Investigate Long-term Safety, Tolerability and Efficacy of GS-100, an Adeno-associated Virus Serotype 9 (AAV9) Vector-mediated Gene Transfer of Human NGLY1, in Patients With NGLY1 Deficiency

Quick Facts

Study Start:2024-02-13

Study Completion:2028-01-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06199531

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:2 Years to 18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Patients must be 2 to 18 years of age, inclusive, at the time of signing the informed consent form (ICF) * Patients with a confirmed diagnosis of NGLY1 Deficiency based on detection of biallelic pathogenic variants in the NGLY1 gene via commercially available molecular genetic sequencing * Patients with at least one of the following signs or symptoms: 1. Global developmental delay and/or intellectual disability 2. Hyperkinetic movement disorder 3. Transient elevation of transaminases 4. (Hypo)alacrima 5. Peripheral neuropathy * For patients with epilepsy who require anti-seizure medications for seizure control: must be on a stable regimen for 28 days prior to enrollment * Patients willing and capable per investigator opinion to comply with study procedures and requirements * Females of childbearing potential must have a negative serum pregnancy test at screening and must agree to use an acceptable method of highly effective contraception from screening through the end of the study * Patients or parent(s)/guardian(s) must be willing and able to provide written consent after the nature of the study has been explained and prior to performance of any research-related procedures	* Patients at Level 5 of both the Gross Motor Function Classification System Expanded and Revised (GMFCS E\&R) and the Communication Function Classification System (CFCS) scales as assessed by the investigator * Contraindication to use of corticosteroids or history of a condition that could worsen with corticosteroid therapy, as assessed, and determined by the investigator * Signs / symptoms of increased intracranial pressure (ICP), history of space occupying lesion, or ventricular shunt that would preclude ICV procedures or safety assessments * Have active malignancy (except non-melanoma skin cancer), autoimmune, metabolic (i.e., diabetes), hematologic, cardiac, or renal disease, or uncontrolled epilepsy, that is of clinical significance defined as requiring regular medical attention or treatment * Vital signs outside age-based normative values: 1. Blood pressure: values \> 99th percentile as cited in the National Heart, Lung and Blood Institute (NHLBI) guidelines for blood pressure levels based on subject's age, height and sex (nhlbi.nih.gov/files/docs/guidelines/child_tbl.pdf) 2. Temperature: evidence of fever such as body temperature (e.g., orally measured) of 38.0°C (100.3°F) 3. Respiratory rate in breaths per minute: toddler (1-3 years old): 24-40; preschooler (4-5 years old): 22-34 breaths per minute; school-aged child (6-12 years old): 18-30 breaths per minute; adolescence (13-18 years old): 12-16. 4. Oxygen saturation on room air \< 92% * Any condition that in the opinion of the investigator or the study medical monitor would prevent the patient from fully complying with the requirements of the study (including the corticosteroid treatment outline in the protocol) and/or would impact or interfere with the evaluation and interpretation of patient safety or efficacy results * Known allergy or hypersensitivity to the GS-100 investigational product formulation * Prior treatment with gene therapy * Treatment with any investigational product (IP) within 30 days or 5 half-lives of the IP, whichever is longer, prior to screening period. For patients who have received a prior investigational product, all ongoing AEs experienced while receiving the investigational product must have been resolved prior to screening for this study * Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study that does not interfere with the requirements of the current protocol and does not have the potential to impact the evaluation of safety and efficacy of GS-100 * Liver dysfunction at screening as defined by the following 1. ALT: \> 3 x upper limit of normal (ULN) 2. aspartate aminotransferase (AST): \> 3 x ULN 3. INR: ≥1.4 x ULN 4. Total bilirubin: \> 2 x ULN unless Gilbert's syndrome is documented * Any current infection with hepatitis B virus (HBV) as evidenced by positive HBV surface antigen (HBsAg), and/or HBV core antibody (HBcAb) at screening. Isolated HBsAb positivity for HBV vaccination in conjunction with negative confirmatory HBV DNA testing at screening is not exclusionary * Any prior or current infection with hepatitis C virus (HCV) as evidenced by positive HCV antibody testing and confirmed by positive polymerase chain reaction (PCR) RNA testing at screening * Any of the following abnormal laboratory values: 1. Hemoglobin level: \< 9 g/dL 2. Absolute neutrophil count: \< 1000 cells/microliter 3. Platelet count: \< 100,000/mm3 4. Creatinine: \> 1.25 x ULN * Have a major surgery planned during the screening period through 52 weeks following GS-100 infusion, including major dental procedures (e.g., wisdom tooth extraction) * Pregnant or breastfeeding female patient * Patients that demonstrate elevated serum adrenocorticotropic hormone (ACTH) 1.5 times the upper limit of normal for the reference range must be referred for consultation with a pediatric endocrinologist to rule out primary adrenal insufficiency prior to being enrolled into the study. Patients may re-screen for participation in the study after medical consultation and / or possible treatment has been initiated to address any adrenal insufficiency

Inclusion Criteria

Exclusion Criteria

* Patients must be 2 to 18 years of age, inclusive, at the time of signing the informed consent form (ICF)
* Patients with a confirmed diagnosis of NGLY1 Deficiency based on detection of biallelic pathogenic variants in the NGLY1 gene via commercially available molecular genetic sequencing
* Patients with at least one of the following signs or symptoms:
1. Global developmental delay and/or intellectual disability
2. Hyperkinetic movement disorder
3. Transient elevation of transaminases
4. (Hypo)alacrima
5. Peripheral neuropathy
* For patients with epilepsy who require anti-seizure medications for seizure control: must be on a stable regimen for 28 days prior to enrollment
* Patients willing and capable per investigator opinion to comply with study procedures and requirements
* Females of childbearing potential must have a negative serum pregnancy test at screening and must agree to use an acceptable method of highly effective contraception from screening through the end of the study
* Patients or parent(s)/guardian(s) must be willing and able to provide written consent after the nature of the study has been explained and prior to performance of any research-related procedures

* Patients at Level 5 of both the Gross Motor Function Classification System Expanded and Revised (GMFCS E\&R) and the Communication Function Classification System (CFCS) scales as assessed by the investigator
* Contraindication to use of corticosteroids or history of a condition that could worsen with corticosteroid therapy, as assessed, and determined by the investigator
* Signs / symptoms of increased intracranial pressure (ICP), history of space occupying lesion, or ventricular shunt that would preclude ICV procedures or safety assessments
* Have active malignancy (except non-melanoma skin cancer), autoimmune, metabolic (i.e., diabetes), hematologic, cardiac, or renal disease, or uncontrolled epilepsy, that is of clinical significance defined as requiring regular medical attention or treatment
* Vital signs outside age-based normative values:
1. Blood pressure: values \> 99th percentile as cited in the National Heart, Lung and Blood Institute (NHLBI) guidelines for blood pressure levels based on subject's age, height and sex (nhlbi.nih.gov/files/docs/guidelines/child_tbl.pdf)
2. Temperature: evidence of fever such as body temperature (e.g., orally measured) of 38.0°C (100.3°F)
3. Respiratory rate in breaths per minute: toddler (1-3 years old): 24-40; preschooler (4-5 years old): 22-34 breaths per minute; school-aged child (6-12 years old): 18-30 breaths per minute; adolescence (13-18 years old): 12-16.
4. Oxygen saturation on room air \< 92%
* Any condition that in the opinion of the investigator or the study medical monitor would prevent the patient from fully complying with the requirements of the study (including the corticosteroid treatment outline in the protocol) and/or would impact or interfere with the evaluation and interpretation of patient safety or efficacy results
* Known allergy or hypersensitivity to the GS-100 investigational product formulation
* Prior treatment with gene therapy
* Treatment with any investigational product (IP) within 30 days or 5 half-lives of the IP, whichever is longer, prior to screening period. For patients who have received a prior investigational product, all ongoing AEs experienced while receiving the investigational product must have been resolved prior to screening for this study
* Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study that does not interfere with the requirements of the current protocol and does not have the potential to impact the evaluation of safety and efficacy of GS-100
* Liver dysfunction at screening as defined by the following
1. ALT: \> 3 x upper limit of normal (ULN)
2. aspartate aminotransferase (AST): \> 3 x ULN
3. INR: ≥1.4 x ULN
4. Total bilirubin: \> 2 x ULN unless Gilbert's syndrome is documented
* Any current infection with hepatitis B virus (HBV) as evidenced by positive HBV surface antigen (HBsAg), and/or HBV core antibody (HBcAb) at screening. Isolated HBsAb positivity for HBV vaccination in conjunction with negative confirmatory HBV DNA testing at screening is not exclusionary
* Any prior or current infection with hepatitis C virus (HCV) as evidenced by positive HCV antibody testing and confirmed by positive polymerase chain reaction (PCR) RNA testing at screening
* Any of the following abnormal laboratory values:
1. Hemoglobin level: \< 9 g/dL
2. Absolute neutrophil count: \< 1000 cells/microliter
3. Platelet count: \< 100,000/mm3
4. Creatinine: \> 1.25 x ULN
* Have a major surgery planned during the screening period through 52 weeks following GS-100 infusion, including major dental procedures (e.g., wisdom tooth extraction)
* Pregnant or breastfeeding female patient
* Patients that demonstrate elevated serum adrenocorticotropic hormone (ACTH) 1.5 times the upper limit of normal for the reference range must be referred for consultation with a pediatric endocrinologist to rule out primary adrenal insufficiency prior to being enrolled into the study. Patients may re-screen for participation in the study after medical consultation and / or possible treatment has been initiated to address any adrenal insufficiency

Contacts and Locations

Study Contact

Regina Deck, RN/MSN/CCRP

CONTACT

805-857-3860

gina@gracescience.com

Study Locations (Sites)

Oakland Children's Hospital (UCSF Benioff)

Oakland, California, 94609

United States

Texas Children's Hospital (Baylor College of Medicine)

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Grace Science, LLC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-02-13

Study Completion Date2028-01-31

Study Record Updates

Study Start Date2024-02-13

Study Completion Date2028-01-31

Terms related to this study

Keywords Provided by Researchers

Gene Therapy
Intervention study
Infusions, Intraventricular
Biomarker
Enzyme Replacement Therapy

Additional Relevant MeSH Terms

NGLY1 Deficiency