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

NCT04271332 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CRA16p201
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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.

Conditions

16P11.2 Deletion Syndrome

Outcome Measures

Primary Outcomes (1)

• Goldman-Fristoe Test of Articulation, 3rd edition (GFTA-3), Sounds-in-Words

  The GFTA-3 is the most widely used, standardized test of articulation for children and adolescents.

  12 weeks

Secondary Outcomes (3)

• Wide Range Assessment of Memory and Learning - 2nd edition (WRAML2)

  12 weeks

• Bruininks-Oseretsky Test - 2nd edition (BOT-2), Fine Motor Control and Body Coordination subtests

  12 weeks

• Differential Ability Scale, 2nd edition (DAS-II)

  12 weeks

Study Arms (2)

Arbaclofen

EXPERIMENTAL

Arbaclofen will be dosed flexibly, with maximum permissible dose depending on age.

Drug: Arbaclofen

Placebo

PLACEBO COMPARATOR

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

Interventions

Arbaclofen DRUG

Arbaclofen tablet

Also known as: R-baclofen, STX209

Arbaclofen

Placebo oral tablet DRUG

Manufactured to match Arbaclofen in size, shape, color and taste

Also known as: Sugar pill

Placebo

Eligibility Criteria

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

You may qualify if:

• Diagnosis of 16p11.2 BP4-BP5 deletion.
• Male or female subjects, 5 through 17 years of age, at Screening.
• Neurodevelopmental disability requiring current educational or other therapeutic support.
• 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.
• All medication regimens must be stable for 30 days prior to Screening.
• 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.
• 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.
• 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.

You may not qualify if:

• Subjects with additional known genetic disorder besides 16p11.2 BP4-BP5 deletion.
• Subjects receiving remote or hybrid schooling at Screening.
• 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).
• 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.
• 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.
• Subjects who plan to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
• Subjects who are currently treated or have been treated with racemic baclofen in the last 30 days.
• Subjects currently treated with antipsychotic medication(s).
• 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.
• 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.
• Subjects currently treated with vigabatrin, tiagabine, or riluzole.
• Subjects taking another investigational drug currently or within the last 30 days.
• Subjects who are not able or willing to take oral disintegrating tablets.
• Subjects who have a history of hypersensitivity to racemic baclofen.
• Subjects who, in the Investigator's opinion, might not be suitable for the study.

Sponsors & Collaborators

• Clinical Research Associates, LLC: lead

Study Sites (4)

Boston Children's Hospital

Boston, Massachusetts, 15031, United States

Location

New York State Psychiatric Institute (NYSPI)

New York, New York, 10032, United States

Location

Texas Children's Hospital

Houston, Texas, 77054, United States

Location

University of Washington

Seattle, Washington, 98915, United States

Location

MeSH Terms

Conditions

16p11.2 Deletion Syndrome

Interventions

arbaclofen placarbil; Sugars

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Paul Wang, MD

  Clinical Research Associates, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo-controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: September 1, 2022
• Primary Completion: December 22, 2024
• Study Completion: March 23, 2025
• Last Updated: May 30, 2024

Record last verified: 2024-05

Locations

US (4)