Low-Dose Ketamine in Children With ADNP Syndrome

NCT04388774 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: GCO 20-1253
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2A, single dose, open-label study to evaluate the safety, tolerability, and efficacy of a low-dose, 40-minute infusion into the veins (intravenous infusion or "IV") of ketamine in children with ADNP syndrome (Activity-Dependent Neuroprotective Protein). The study team will enroll 10 participants, ages 5 to 12, at Mount Sinai. The study participation is expected to last 4 weeks and will include 5 scheduled clinic visits in order to complete safety monitoring, clinical assessments, and biomarker collection. At the conclusion of this study, the study team expects to demonstrate the safety and tolerability of low-dose ketamine in children with ADNP syndrome. Additionally, the study team anticipates identifying meaningful signals of efficacy in clinical outcome measures using RNA and DNA sequencing to analyze ADNP protein expression and DNA methylation profiles, a natural process by which methyl groups are added to the DNA to change its activity, in order to assess sensitivity to change with low-dose ketamine treatment and inform future phase 3 studies. Ketamine is not currently approved by the Food and Drug Administration to treat this syndrome, but it is approved for use in children in other situations, for example in anesthesia.

Conditions

ADNP Syndrome

Keywords

Ketamine; ADNP; Activity-Dependent Neuroprotector Protein; Chromosome Disorders; Chromosome Aberrations

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Adverse Event

  Number of Participants with an adverse event as defined by the Systematic Longitudinal Assessment of Adverse Events (SLAES) which is a comprehensive form that assesses medical and behavioral conditions that were present at screening and/or baseline. Conditions are considered treatment emergent if their severity increased significantly after the participant had taken at least one dose of the study treatment. Treatment emergent adverse events will be tracked considered in the adverse event safety analysis. Severity of adverse events are categorized as mild, moderate, severe, life-threatening, or resulting in death and the treating physician indicates if the adverse event was related or unrelated to study drug.

  Week 4

Secondary Outcomes (12)

• Aberrant Behavior Checklist

  Baseline, Week 1

• Anxiety, Depression and Mood Scales (ADAMS)

  Baseline and Week 1

• Repetitive Behavior Scale-Revised (RBS-R)

  Baseline, Week 1

• Clinical Global Impressions - Improvement Scale (CGI-I)

  Baseline, Week 2, and Week 4

• Childrens Sleep Habits Questionnaire

  Baseline, Week 1

Study Arms (1)

Ketamine

EXPERIMENTAL

Total dose administration or 0.5 mg/kg of ketamine

Drug: Ketamine

Interventions

Ketamine DRUG

A single 40-minute intravenous infusion

Ketamine

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• to 12 years old (inclusive) at the time of informed consent;
• Has a diagnosis of ADNP syndrome, confirmed by genetic testing prior to subject randomization;
• Has a Clinical Global Impression-Severity score of 4 (moderately ill) or greater at screening;
• Any concomitant medication, including anti-epileptic and/or behavioral medications, supplements, and special diets, must be at a stable dose for at least 4 weeks before;
• Has an English-speaking caregiver capable of providing informed consent and able to attend all scheduled study visits, oversee the administration of study drug, and provide feedback regarding the subject's behavior and other symptoms as described in the protocol;
• Provide assent to the protocol (when applicable);
• Has a caregiver who will agree not to post any of the subject's personal medical data related to the study or information related to the study on any website or social media site (e.g., Facebook and Twitter) until they have been notified that the study is completed.

You may not qualify if:

• Has a concomitant disease (e.g., gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or any clinically significant finding at screening that could interfere with the conduct of the study or that would pose an unacceptable risk to the subject in this study;
• Has clinically significant lab abnormalities or vital signs at the time of screening (e.g., alanine aminotransferase or aspartate aminotransferase \>2.5 × upper limit of normal; total bilirubin or creatinine \>1.5 × upper limit of normal). Re-testing of safety labs is allowed;
• Hypertension that is not well controlled (systolic BP \>130-140 mm Hg or diastolic BP \>85-95 mm Hg depending on age);
• A blood pressure reading over 160/90 or two separate readings over 140/90 at screening or baseline visits;
• Thyroid impairment, as reflected by a TSH \> 4.2 mU/L;
• Cardiac disease, as reflected by an EKG that is abnormal and of concern for cardiac disease;
• Has had changes in his/her medication regimen within the previous month;
• Has a history of uncontrollable seizure disorder or seizure episodes within 1 month of screening;
• Has a history of suicidal behavior or considered by the investigator to be at high risk of suicide;
• Has a current or past history of psychotic symptoms;
• Has enrolled in any clinical trial or used of any investigational agent, device, and/or investigational procedure within the 30 days before screening or does so concurrently with this study.

Sponsors & Collaborators

• Alexander Kolevzon: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Chromosome Disorders; Chromosome Aberrations

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Dr. Alexander Kolevzon
• Organization: Icahn School of Medicine at Mount Sinai

alexander.kolevzon@mssm.edu

(212) 659-8762

Study Officials

• Alexander Kolevzon, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 12, 2020
• First Posted: May 14, 2020
• Study Start: August 19, 2020
• Primary Completion: June 8, 2021
• Study Completion: June 8, 2021
• Last Updated: July 7, 2023
• Results First Posted: July 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)