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A Study of the Safety and Tolerability of GTX-102 in Children With Angelman Syndrome (KIK-AS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04259281
Recruitment Status : Recruiting
First Posted : February 6, 2020
Last Update Posted : February 18, 2020
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
GeneTX Biotherapeutics, LLC

Brief Summary:
This is a Phase 1/2, open-label, multiple-dose, dose-escalating study to evaluate the safety, tolerability, and plasma and cerebrospinal fluid (CSF) concentrations of GTX-102 in pediatric patients with Angelman syndrome. Approximately 20 patients (male and female) ≥ 4 and ≤ 17 years of age with a genetically confirmed diagnosis of full maternal UBE3A gene deletion (within 15q11.2-q13 region) will be enrolled.

Condition or disease Intervention/treatment Phase
Angelman Syndrome Drug: GTX-102 Phase 1 Phase 2

Detailed Description:

This is a Phase 1/2, open-label, multiple-dose, dose-escalating study to evaluate the safety, tolerability, and plasma and CSF concentrations of GTX-102 in pediatric patients with AS.

The study includes screening, baseline, treatment, and safety follow-up periods. Eligible patients who meet all of the inclusion criteria and none of the exclusion criteria and who successfully complete all screening and baseline assessments will be assigned to one of 5 sequential dose cohorts. GTX-102 will be administered by intrathecal (IT) injection via lumbar puncture (LP) at Baseline followed by 3 subsequent IT injections on study Days 30, 58 and 86. The procedure for IT administration of GTX-102 will performed by a clinician with experience in LP and anesthetic care will be directed by experienced anesthesiologists with a focus on patient safety and comfort. The total duration of study for each patient is anticipated to be approximately 6 months. An open-label extension (OLE) study will be conducted under a separate protocol where patients can receive continued treatment with GTX-102.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-label, Multiple-dose, Dose-escalating Clinical Trial of the Safety and Tolerability of GTX-102 in Pediatric Patients With Angelman Syndrome (AS)
Estimated Study Start Date : February 2020
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GTX-102 Cohort 1
Dose A
Drug: GTX-102
antisense oligonucleotide

Experimental: GTX-102 Cohort 2
Dose B
Drug: GTX-102
antisense oligonucleotide

Experimental: GTX-102 Cohort 3
Dose C
Drug: GTX-102
antisense oligonucleotide

Experimental: GTX-102 Cohort 4
Dose D
Drug: GTX-102
antisense oligonucleotide

Experimental: GTX-102 Cohort 5
Dose E
Drug: GTX-102
antisense oligonucleotide




Primary Outcome Measures :
  1. Safety: incidence of adverse events [ Time Frame: Day 128 (end of study) ]
    Number of patients with adverse events (AEs)

  2. Safety: incidence of serious adverse events [ Time Frame: Day 128 (end of study) ]
    Number of patients with serious adverse events (SAEs)

  3. Safety: severity of adverse events [ Time Frame: Day 128 (end of study) ]
    Severity of AEs


Secondary Outcome Measures :
  1. Pharmacokinetics of GTX-102 [ Time Frame: Day 2, Day 3, Day 4, Day 30, Day 58, Day 86, Day 128 (end of study) ]
    Maximum drug concentration (Cmax)


Other Outcome Measures:
  1. Pharmacodynamics of GTX-102 [ Time Frame: Day 86 ]
    UBE3A protein levels in CSF

  2. Exploratory: Change in motor function by wearable device [ Time Frame: Day 128 (end of study) ]
    Ambulation measured by wearable device

  3. Exploratory: Change in development [ Time Frame: Change from baseline to Day 128 (end of study) on total score ]
    Developmental assessment by Bayley Scales of Infant/Toddler Development 4 (BSID-4)

  4. Exploratory: Change in communication [ Time Frame: Change from baseline to Day 128 (end of study) on total score ]
    Observer Reported Communication Assessment (ORCA)

  5. Exploratory: Seizure frequency [ Time Frame: Day 128 (end of study) ]
    Seizure frequency by diary

  6. Exploratory: Change in sleep [ Time Frame: Day 128 (end of study) ]
    Assessment of sleep by diary

  7. Exploratory: Change in behaviors [ Time Frame: Day 128 (end of study) ]
    Aberrant Behaviors Check List Community Version (ABC-C)

  8. Exploratory: Adaptive behaviors [ Time Frame: Change from baseline to Day 128 (end of study) on total score ]
    Vineland Adaptive Behaviors Scale-3 (VABS-3)

  9. Exploratory: Global Clinical Status [ Time Frame: Day 128 (end of study) ]
    Clinical Global Impression of Severity - Angelman syndrome version (CGI-S-AS)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   4 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent from parent(s) or legal guardian(s)
  • Documented genetic confirmation of full maternal UBE3A gene deletion causing AS (e.g. DNA methylation testing with either a chromosomal microarray or FISH) in the region of 15q11.2-q13 including class I, II or III).
  • Age ≥ 4 to ≤ 17 years at screening
  • Stable seizure control (defined as clinically stable with no changes in antiepileptic medications over the prior 1 month before screening visit, other than weight associated dose adjustments)
  • Platelet count, prothrombin time (PT) / international normalized ratio (INR) and partial thromboplastin time (PTT) within normal limits
  • Normal renal function with serum creatinine and spot urine protein within normal limits
  • Normal hepatic function with total bilirubin, aspartate aminotransferase (AST),alanine aminotransferase (ALT) and alkaline phosphatase within normal limits
  • Willing and able to comply with scheduled visits, drug administration plan, laboratory tests, study restrictions, and all study procedures LP.
  • Able to tolerate the anesthetic regimen required for LP procedure

Exclusion Criteria:

  • Any change in medications (excluding antiepileptic drugs) or diet intended to treat symptoms of AS (e.g. sleeping aids, supplements, ketogenic or low-glycemic index diet, other) over the prior 3 months before screening.
  • Inability to ambulate independently or with an assistive device or caregiver hand-hold
  • Any bleeding or platelet disorder
  • Any clinically significant (CS) cardiovascular, endocrine, hepatic, renal, pulmonary, gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition that, in the judgment of the Investigator, will pose a safety risk, will make the patient unsuitable for participation in, and/or unable to complete the study procedures.
  • Any laboratory abnormality, that, in the Investigator's opinion, could adversely affect the safety of the patient, make it unlikely that the course of treatment or follow up would be completed, or impair the assessment of study result
  • Any active infection
  • Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture
  • Drugs that increase the risk of bleeding (e.g. heparin, low molecular weight heparin, platelet inhibitors).
  • Use of any investigational oligonucleotide in the past 6 months
  • Any prior use of gene therapy
  • Use of any investigational drugs in the past 6 months
  • Any medical condition that would require intubation for the anesthesia procedure

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04259281


Contacts
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Contact: Scott Stromatt, MD 206-225-6749 info@genetxbio.com

Locations
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United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Haley Richter       haley_e_richter@rush.edu   
Sponsors and Collaborators
GeneTX Biotherapeutics, LLC
Ultragenyx Pharmaceutical Inc

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Responsible Party: GeneTX Biotherapeutics, LLC
ClinicalTrials.gov Identifier: NCT04259281    
Other Study ID Numbers: GTX-102-001
First Posted: February 6, 2020    Key Record Dates
Last Update Posted: February 18, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Angelman Syndrome
Syndrome
Disease
Pathologic Processes
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn