Updated 2024-04-10 with current trial sites and expanded age range. Additional sites will be added here as they open.
Tetra Therapeutics is accepting males ages 9-45 with Fragile X syndrome for large scale clinical phase 3 trials of their phosphodiesterase (PDE) inhibitor
Individuals who complete the placebo-controlled trial are then eligible to continue taking the drug, as part of an open label continuation trial.
These trials mark a major milestone for community-based drug development. FRAXA-funded research pointed the way to phosphodiesterase inhibitors to treat Fragile X many years ago. However, finding a good phosphodiesterase (PDE) inhibitor was a challenge because there was so much interest in the pharmaceutical world in developing these drugs for Alzheimer's disease and other blockbuster indications.
FRAXA then partnered with Tetra Therapeutics to test their advanced PDE 4D inhibitor in Fragile X mice, with remarkable results.
The results in the mice justified clinical trials, so FRAXA and Tetra organized and co-funded the first Fragile X trials of this investigational drug. The outcome was a genuine breakthrough for the field: statistically significant improvement in Fragile X subjects on a wide range of outcome measures. Behavior improved, quality of life improved, electrophysiology improved, and most importantly of all, cognition improved markedly. There are no drugs currently approved to treat intellectual disability.
If the new trials are successful, our community could see the first approved treatment for Fragile X syndrome on the market.
Enrollment Information
Participation in this clinical trial includes reimbursement for expenses. This can include prepaid travel arrangements (transportation and hotel accommodation) and meal expenses, subject to certain restrictions.
To Sign Up for this Fragile X clinical trial, contact a location listed below.
UC Davis Health System
Davis, CA
Accepting males ages 9-45
Abigail Borbe
amoradelhigareda@ucdavis.edu
(916) 703-0281
Amnova Clinical Research
Irvine, CA
Accepting males ages 9-45
Maggie Wang
maggie@amnovaresearch.com
CHOC Thompson Autism Center
Orange, CA
Accepting males ages 9-45
Elyssa Smith
Elyssa.smith@choc.org
(714) 509-8300 x32683
Children's Hospital Colorado
Aurora, CO
Accepting males ages 9-45
Erika Peterson
erika.peterson@childrenscolorado.org
(720) 777-8590
Emory University
Atlanta, GA
Accepting males ages 9-45
Jean Luan McColl
jean.luan@emory.edu
(864) 678-6912
Rush University
Chicago, IL
Accepting males ages 9-45
Abigail Ayemoba
Abigail_ayemoba@rush.edu
University of Kansas Medical Center
Kansas City, KS
Accepting males ages 9-45
Jasi Bonilla
jbonilla@kumc.edu
(913) 945-9790
UMass Chan Medical School
Worcester, MA
Accepting males ages 9-45
Taylor Merk
Taylor.Merk@umassmed.edu
(774) 455-4119
Kennedy Krieger Institute
Baltimore, MD
Accepting males ages 9-45
Maria Halaguena
halaguena@kennedykrieger.org
(443) 923-3826
Icahn School of Medicine
New York, NY
Accepting males ages 9-45
Venus Fan
venus.fan@mssm.edu
(929) 989-7016
Cincinnati Children's Hospital Medical Center
Cincinnati, OH
Accepting males ages 9-45
Jessica Michael
Jessica.michael@cchmc.org
(513) 517-1550
Suburban Research Associates
Media, PA
Accepting males ages 9-45
Meghan Verano
mvarano@suburbanresearch.com
Online Application
Clinic for Special Children
Strasburg, PA
Accepting males ages 9-45
Karlla Brigatti
kbrigatti@clinicforspecialchildren.org
Greenwood Genetic Center
Greenwood, SC
Accepting males ages 9-18
Nicole Johnston
njohnston@ggc.org
(864) 678-6912
University of Utah/Primary Children's Hospital
Salt Lake City, UT
Accepting males ages 9-18
Hina Yazdani
hina.yazdani@hsc.utah.edu
July 12, 2022 – Grand Rapids, MI – Tetra Therapeutics, a Shionogi Group Company, focused on the development of compounds for the treatment of brain disorders associated with cognitive and memory deficits, today announced the initiation of three Phase 2b/3 clinical studies of the investigational drug BPN14770 (zatolmilast) as a potential treatment for Fragile X syndrome (FXS), the most common genetic form of autism. A selective small molecule inhibitor of phosphodiesterase-4D (PDE4D), BPN14770 has shown positive results in a previous Phase 2 study in FXS in adult males (Berry-Kravis EM, et al. Inhibition of phosphodiesterase-4D in adults with Fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial. Nat Med. 2021;27(5):862-870.). BPN14770 has also received Orphan Drug Designation from the US Food and Drug Agency (FDA) for the potential treatment of FXS.
The Phase 2b/3 studies comprise two separate 150 subject, randomized, double-blind, placebo-controlled studies: one in an adolescent male population (ages 12-17), one in an adult male population (18-45), and a third open label extension study open to patients in both populations at the conclusion of the primary study. Endpoints for the studies include cognitive and behavioral assessments of the efficacy of BPN14770 by a variety of standard tests and determinations of the experimental drug’s safety and tolerability. The study will also gather pharmacokinetic data on BPN14770. The studies are being conducted at multiple sites across the United States lead by principal investigator Elizabeth M. Berry-Kravis, MD, PhD at Rush University Medical Center, Chicago, Illinois. The studies are expected to be conducted over the next two years. Additional information is available through clinicaltrials.gov (Identifiers: NCT05163808, NCT05358886, NCT05367960).
“We are excited to initiate these pivotal trials with BPN 14770 in patients with Fragile X syndrome, and are hopeful that the results of these studies will enable us to seek approval from FDA,” said Chad Coberly, JD, Chief Executive Officer of Tetra Therapeutics.”
“We are anxious to get started with these studies that offer hope for people living with Fragile X syndrome and their caregivers” said Dr. Elizabeth Berry-Kravis, pediatric neurologist, Rush University Medical Center, and principal investigator. “Given our previous positive results with BPN14770 in the phase 2 study, we are hopeful these studies at a larger scale will show similar results. I find it exciting that we have a drug that potentially corrects a core deficit in FXS, a decrease in cAMP, that has been documented in patients as well as in the fly and mouse models of the disorder.”
About BPN14770
BPN14770 is an investigational new drug that selectively inhibits phosphodiesterase-4D to enhance early and late stages of memory formation. Preclinical animal models show that BPN14770 has the potential to promote the maturation of connections between neurons, which is impaired in patients with FXS, and to protect connections between neurons which otherwise are lost in patients with Alzheimer’s Disease. Tetra has completed investigational Phase 2 studies of BPN14770 in adults with FXS and in Alzheimer’s disease. BPN14770 also has received Orphan Drug Designation from the US Food and Drug Administration (FDA).
About Tetra Therapeutics
Tetra Therapeutics, a Shionogi Group Company, is a clinical stage biotechnology company focused on developing a portfolio of therapeutic products to people suffering from Fragile X syndrome, Alzheimer's disease, traumatic brain injury, and other brain disorders. Tetra Therapeutics is headquartered in Grand Rapids, Michigan. For more information, please visit the company's website at www.tetratherapeutics.com.
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.
Post Revisions
- 2024/02 - Updated to include new age range, protocol amendments and additional recruiting sites.
- 2023/10 - Updated to include open label extension trial.
- 2023/06 - Updated with additional recruiting sites.
- 2022/10 - Updated as clinical trial now recruiting at first location.
- 2022/07 - Original post published.
