This is the classic website, which will be retired eventually. Please visit the modernized instead.
Working… Menu

Safety, Tolerability, and Efficacy of Arbaclofen in 16p11.2 Deletion

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. Identifier: NCT04271332
Recruitment Status : Recruiting
First Posted : February 17, 2020
Last Update Posted : April 19, 2023
Information provided by (Responsible Party):
Clinical Research Associates, LLC

Brief Summary:
This Phase 2 study examines the safety, tolerability, and efficacy of arbaclofen in pediatric subjects with 16p11.2 deletion. Male or female subjects aged 5 to 17 years of age will be randomized to receive either placebo or arbaclofen in a double-blind study design. If the subject completes all study requirements through Visit 4 (Close-out Visit), he/she may be eligible for an optional open-label study with arbaclofen.

Condition or disease Intervention/treatment Phase
16P11.2 Deletion Syndrome Drug: Arbaclofen Drug: Placebo oral tablet Phase 2

Detailed Description:

This study will enroll male or female subjects, aged 5 to 17 years, who have the 16p11.2 bp4-bp5 deletion. Subjects will be randomized to treatment with either placebo or arbaclofen. Subjects and study staff will be blinded to treatment assignment throughout the study. Both placebo and arbaclofen will be administered as orally disintegrating tablets. Dosing will be flexible, with subjects titrating up to the highest tolerated dose, with maximum permissible dose dependent on age. The treatment period is 16 weeks, after which subjects will taper off of study drug. Subjects will be required to attend multiple study visits, and to communicate with the study staff by phone multiple times throughout the study.

The primary efficacy assessment focuses on speech. Secondary and exploratory endpoints assess motor, memory, general cognitive, and other neuropsychological abilities, and brain electrophysiology. The safety evaluations include blood tests, physical exam, and assessment of adverse events.

Subjects who complete study participation through the end of the Withdrawal Period may be eligible to enroll in a subsequent open-label study. Dosing will be flexible, with subjects titrating up to the highest tolerated dose, with maximum permissible dose dependent on age. The treatment period is 16 weeks, after which subjects will taper off arbaclofen.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Placebo-controlled
Primary Purpose: Treatment
Official Title: An Exploratory, Randomized, Double-Blind, Placebo-Controlled and Open-label Extension Study of the Safety, Tolerability, and Efficacy of Arbaclofen in Subjects With 16p11.2 Deletion
Actual Study Start Date : September 1, 2022
Estimated Primary Completion Date : December 22, 2024
Estimated Study Completion Date : March 23, 2025

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arbaclofen
Arbaclofen will be dosed flexibly, with maximum permissible dose depending on age.
Drug: Arbaclofen
Arbaclofen tablet
Other Names:
  • R-baclofen
  • STX209

Placebo Comparator: Placebo
The placebo tablet is manufactured to match arbaclofen in shape, size, color, and taste, and will be administered in the same manner as arbaclofen.
Drug: Placebo oral tablet
Manufactured to match Arbaclofen in size, shape, color and taste
Other Name: Sugar pill

Primary Outcome Measures :
  1. Goldman-Fristoe Test of Articulation, 3rd edition (GFTA-3), Sounds-in-Words [ Time Frame: 12 weeks ]
    The GFTA-3 is the most widely used, standardized test of articulation for children and adolescents.

Secondary Outcome Measures :
  1. Wide Range Assessment of Memory and Learning - 2nd edition (WRAML2) [ Time Frame: 12 weeks ]
    The WRAML2 is a standardized test that measures memory functioning.

  2. Bruininks-Oseretsky Test - 2nd edition (BOT-2), Fine Motor Control and Body Coordination subtests [ Time Frame: 12 weeks ]
    The BOT-2 is an individually administered, comprehensive measure of gross and fine motor skills.

  3. Differential Ability Scale, 2nd edition (DAS-II) [ Time Frame: 12 weeks ]
    The DAS-II is an individually-administered clinical instrument for assessing the cognitive abilities that are important to learning.

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.

Layout table for eligibility information
Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:To be eligible to participate in this study, all of the following criteria must be met:

  1. Diagnosis of 16p11.2 BP4-BP5 deletion.
  2. Male or female subjects, 5 through 17 years of age, at Screening.
  3. Neurodevelopmental disability requiring current educational or other therapeutic support.
  4. Any educational, behavioral, other therapeutic, and/or dietary interventions must have been continuous during the 2 months prior to Screening (with the exception of the anti-epileptic drug (AED) 6-month requirement in Inclusion Criterion #5). Subjects and their parent/caregiver/legally authorized representative (LAR) may not electively initiate new, or modify ongoing, interventions for the duration of the study. Typical school vacations are not considered modifications of stable programming.
  5. Subjects with a history of seizure disorder must have been seizure-free and on a stable antiepileptic therapy regimen for 6 months OR must have been seizure-free for the 3 years prior to Screening if not currently receiving antiepileptics. If currently receiving treatment with antiepileptics that are typically monitored by serum concentration, serum concentrations of the antiepileptic drugs must be tested and confirmed to be within the therapeutic range at Screening.
  6. All medication regimens must be stable for 30 days prior to Screening.
  7. Prior to the conduct of any study-specific procedures, the subject must provide assent to participate in the study (if developmentally appropriate), and the parent/caregiver/LAR must provide written informed consent. If the caregiver attending the clinic visits is not the parent or LAR, written consent must also be obtained from the parent or LAR for the subject's participation in the study.
  8. The subject's parent/caregiver/LAR must be able to speak and understand English sufficiently to understand the nature of the study and to allow for the completion of all study assessments. The parent/caregiver/LAR should be capable of providing reliable information about the subject's condition, agree to oversee the administration of the study drug, and accompany the subject to all clinic visits. The same parent/caregiver/LAR should accompany the subject to each visit.
  9. Negative pregnancy test for females who are 9 years of age or older. Both male and female subjects who are sexually active must agree to consistently use an accepted form of contraception (i.e., surgical sterilization, intrauterine contraceptive device, subcutaneous implant, oral contraceptive, or diaphragm or condom in combination with contraceptive cream/jelly, or abstinence) throughout the trial and for 30 days (females) or 90 days (males) following last study drug administration.

Exclusion Criteria:Subjects are not permitted to enroll in the study if any of the following criteria are met:

  1. Subjects with additional known genetic disorder besides 16p11.2 BP4-BP5 deletion.
  2. Subjects receiving remote or hybrid schooling at Screening.
  3. Subjects with an additional neurologic or psychiatric condition that might confound performance on assessments measures, e.g., significant impairment in hearing or vision, severe motor impairment (e.g., non-ambulatory) from cerebral palsy, birth injury, or other injury, or cleft lip or palate (including submucous cleft).
  4. Subjects with any seizures within the previous 6 months; subjects who are not currently receiving antiepileptics AND have had one or more seizures during the 3 years prior to Screening; and subjects who are shown to have non-therapeutic AED levels at Screening.
  5. Subjects with any medical or psychiatric condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. This includes, but is not limited to substance use disorders, impairment of renal function, evidence or history of malignancy or any significant hematological, endocrine, cardiovascular, respiratory, hepatic, or gastrointestinal disease.
  6. Subjects who plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
  7. Subjects who are currently treated or have been treated with racemic baclofen in the last 30 days.
  8. Subjects currently treated with antipsychotic medication(s).
  9. Subjects currently treated with more than 2 psychoactive medications, including antiepileptics used as an anti-seizure treatment, but not including sleep aids used on an as-needed basis.
  10. Subjects currently treated with drugs having anxiolytic properties, including but not limited to: buspirone and beta-blockers. Benzodiazepines administered on a regular schedule (more than 3x/week) are not permitted. Use of antidepressants may be permitted with approval of the Medical Monitor. Other prohibited and restricted medications are shown in Appendix A.
  11. Subjects currently treated with vigabatrin, tiagabine, or riluzole.
  12. Subjects taking another investigational drug currently or within the last 30 days.
  13. Subjects who are not able or willing to take oral disintegrating tablets.
  14. Subjects who have a history of hypersensitivity to racemic baclofen.
  15. Subjects who, in the Investigator's opinion, might not be suitable for the study.

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 identifier (NCT number): NCT04271332

Layout table for location contacts
Contact: Paul Wang, MD 860-961-6022.
Contact: Karen Walton-Bowen 917.239.4745

Layout table for location information
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 15031
Contact: Meaghan Dyer    617-355-8300   
Principal Investigator: Lisa Prock, MD         
United States, New York
New York State Psychiatric Institute (NYSPI) Recruiting
New York, New York, United States, 10032
Contact: Alyssa Verdes    914-997-5532   
Contact: Suvekcha Bhattachan    914-997-5532   
Principal Investigator: Jeremy Veenstra-VanderWeele, MD         
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77054
Contact: Ivana Lozano    832-824-8364   
Principal Investigator: Robin Kochel, Phd         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98915
Contact: Erin Royal    206-616-1181   
Sponsors and Collaborators
Clinical Research Associates, LLC
Layout table for investigator information
Study Director: Paul Wang, MD Clinical Research Associates, LLC
Layout table for additonal information
Responsible Party: Clinical Research Associates, LLC Identifier: NCT04271332    
Other Study ID Numbers: CRA16p201
First Posted: February 17, 2020    Key Record Dates
Last Update Posted: April 19, 2023
Last Verified: April 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
GABA-B Receptor Agonists
GABA Agonists
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action