Recruiting: Tetra Therapeutics Phase 3 Clinical Trial of Zatolmilast in Fragile X Syndrome

Two Tetra Therapeutics studies are recruiting males aged 9 to 45 to participate in potential registration trials for a new treatment for Fragile X syndrome (FXS), to be followed by a 2-year open label extension study in which all subjects will receive active treatment.

BPN14770-CNS-204 

• Adolescent males 9 to 17 years, weighing ≥ 55 lbs and ≤ 97 percentile of BMI for age
• Double-blind
• Randomized 2 active : 1 placebo
• 13 weeks treatment

BPN14770-CNS-301

• Adult males 18-45 years, with BMI between 18-36 kg/m²
• Double-blind
• Randomized 2 active : 1 placebo
• 13 weeks treatment

BPN14770-CNS-302

• 2-year open label extension
• for subjects who complete studies 204 or 301 through Week 13

Primary Eligibility Criteria

• FXS with a molecular genetic confirmation FMR1 >200 CGG repetitions.
• Current treatment with < 3 psychotropic medications. Anti-epileptics don’t count as psychotropic if used for treatment of seizures.
• Permitted psychotropics must be at a stable dose for at least 4 weeks prior to screening and must remain stable.
• Anti-epileptic medications must be at a stable dose for 12 weeks before screening and must remain stable.
• Subjects with a history of seizure currently receiving treatment must be seizure-free for 3 months prior to screening, or 2 years if not on treatment.
• Behavioral/non-pharmacological treatments stable for 4 weeks prior to screening and must remain stable.
• Subject must be willing to practice barrier methods of contraception or be abstinent.
• Must have consistent caregiver who can attend all visits. 

Overview of Visit Schedule

BPN14770-CNS-204/301 Assessments

• Screening (14 to 28 days before Day 1)
• Day 1 - Baseline 
• Week 1 - Telephone call
• Week 4 - Safety * 
• Week 8 - Safety and Efficacy 
• Week 10 - Safety *
• Week 13 - Safety and Efficacy
• Week 14 - Follow up telephone call – only if not entering BPN14770-CNS-302 Open Label Extension

BPN14770-CNS-302 Assessments

• Day 1 (same as Week 13 of 204/301)
• Week 1 - Safety (phone call)
• Weeks 4, 8, 10, 17, 21, 39 - Safety *
• Weeks 65, 91 - Safety (phone call)
• Weeks 13, 26, 52, 78, 104 - Safety and Efficacy 
• Week 106 - Follow up telephone call

* These safety-only visits may be completed remotely using a sponsor-provided visiting nurse service, followed by a call from the clinic.

Screening and Day 1 visits and post-treatment visits to assess both safety and efficacy are expected to last 4-6 hours. Home-based, remote nursing visits to assess safety will generally last about an hour and will be followed by a phone call from the clinical site.

Other than routine blood draws, there are no invasive procedures or scans in these studies. Subjects will complete an IQ test at screening, and a portion of the same test at later visits; subjects will also complete cognitive assessments on an iPad.

Caregivers will be asked to assess overall improvement, as well as specific improvement in daily living, language, academic skills (adolescents only) , and emotions/behaviors. Caregivers will also be asked to complete the Vineland-3, ABC and ADAMS assessment tools.

Participants will be provided fully coordinated travel support at no cost to families.

About BPN14770 (Zatolmilast)

BPN14770, also known as zatolmilast, is a selective PDE4D negative allosteric modulator being developed for the treatment of FXS,
Alzheimer’s disease, and other cognitive disorders.

A previous Phase 2a study in FXS (adults males, n=30) comparing BPN14770 25 mg to placebo dosed twice daily showed:

• Statistically significant changes in performance-based and parentrated scales on measures of communication and language
• A consistent advantage across diverse clinical domains (including cognitive and behavioral) on parent-rated, clinician-rated and
  performance measures
• BPN14770 was well-tolerated, with no serious or severe adverse events related to treatment.