BPN14770 for Fragile X Syndrome
Recruiting in Palo Alto (17 mi)
+25 other locations
Age: 18 - 65
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Tetra Discovery Partners
Disqualifiers: Renal impairment, Hepatic impairment, Substance abuse, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a medication called BPN14770 in men aged 18 to 45 who have Fragile X Syndrome. The medication aims to improve brain function by balancing chemicals that help with thinking and memory.
Will I have to stop taking my current medications?
The trial allows participants to continue taking up to three prescribed psychotropic medications, as long as the doses have been stable for at least 4 weeks before the screening and remain stable during the study. Anti-epileptic medications are also allowed if they are stable for 12 weeks before screening.
How is the drug BPN14770/zatolmilast unique for treating Fragile X Syndrome?
BPN14770/zatolmilast is unique because it targets a different mechanism in the brain compared to other treatments, potentially offering a new approach to managing Fragile X Syndrome. While other drugs like mavoglurant focus on blocking specific receptors (mGluR5), BPN14770/zatolmilast may work through different pathways, providing an alternative option for patients.
12345Eligibility Criteria
This trial is for male adults aged 18 to 45 with Fragile X Syndrome who can swallow capsules and have stable medication regimens. They must not be participating in other trials, have significant diseases or impairments that could affect results, or a history of substance abuse within the last year. If sexually active, they should use barrier contraception.Inclusion Criteria
I have Fragile X Syndrome confirmed by a genetic test.
Subject must be willing to practice barrier methods of contraception while on the study if sexually active. Abstinence is also considered a reasonable form of birth control in this study population
Subject and caregiver are able to attend the clinic regularly and reliably
+11 more
Exclusion Criteria
I am starting or have recently started psychotherapy or cognitive behavior therapy.
I do not have active conditions like AIDS, hepatitis B, hepatitis C, or tuberculosis.
My liver tests are more than twice the normal limit.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either 25mg BID BPN14770 or placebo for 13 weeks
13 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests BPN14770 (zatolmilast), comparing it against a placebo in a randomized, double-blind setup. Participants won't know if they're getting the actual drug or a dummy pill as researchers observe its effects on males with Fragile X Syndrome.
2Treatment groups
Active Control
Placebo Group
Group I: Study DrugActive Control1 Intervention
25mg BID BPN14770
Group II: PlaceboPlacebo Group1 Intervention
Placebo
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Amnova Clinical ResearchIrvine, CA
Phoenix Childrens Hospital Barrow Neurological InstitutePhoenix, AZ
Clinic for Special ChildrenStrasburg, PA
Kennedy Krieger InstituteBaltimore, MD
More Trial Locations
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Who Is Running the Clinical Trial?
Tetra Discovery PartnersLead Sponsor
References
Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. [2016]Fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autistic spectrum disorder, is typically caused by transcriptional silencing of the X-linked FMR1 gene. Work in animal models has described altered synaptic plasticity, a result of the up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling, as a putative downstream effect. Post hoc analysis of a randomized, placebo-controlled, crossover phase 2 trial suggested that the selective mGluR5 antagonist mavoglurant improved behavioral symptoms in FXS patients with completely methylated FMR1 genes. We present the results of two phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies of mavoglurant in FXS, designed to confirm this result in adults (n = 175, aged 18 to 45 years) and adolescents (n = 139, aged 12 to 17 years). In both trials, participants were stratified by methylation status and randomized to receive mavoglurant (25, 50, or 100 mg twice daily) or placebo over 12 weeks. Neither of the studies achieved the primary efficacy end point of improvement on behavioral symptoms measured by the Aberrant Behavior Checklist-Community Edition using the FXS-specific algorithm (ABC-C(FX)) after 12 weeks of treatment with mavoglurant. The safety and tolerability profile of mavoglurant was as previously described, with few adverse events. Therefore, under the conditions of our study, we could not confirm the mGluR theory of FXS nor the ability of the methylation state of the FMR1 promoter to predict mavoglurant efficacy. Preclinical results suggest that future clinical trials might profitably explore initiating treatment in a younger population with longer treatment duration and longer placebo run-ins and identifying new markers to better assess behavioral and cognitive benefits.
A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. [2022]A pilot open label, single dose trial of fenobam, an mGluR5 antagonist, was conducted to provide an initial evaluation of safety and pharmacokinetics in adult males and females with fragile X syndrome (FXS).
Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome. [2013]We conducted a randomized, double-blind, placebo-controlled crossover study of folinic acid therapy (dl-Leucovorin, 15 mg/day) or placebo for males with Fragile X (fra(x)) syndrome. Twenty-one patients were enrolled in the study. The treatment periods were 3 months in length. Patients were followed with chemistry panels and complete blood counts. No differences between placebo and treatment phases were noted in any laboratory parameter. Instruments to measure functioning were the Vineland Adaptive Behavioral Scales, Peabody Picture Vocabulary Test-Revised, Conners Parent and Teaching Rating Scales, the ADD-H: Comprehensive Teacher's Rating Scales (ACTeRS), and a questionnaire designed by the investigators. At the crossover point, 2 parents requested to withdraw from the study because they felt their children had made dramatic gains during the first half of the study and had lost those gains after the crossover point. Both parents had accurately predicted that their sons were receiving folinic acid during the first half of the study. However, no statistically significant differences could be demonstrated between the treatment and placebo phases of the study with any instrument when the results were averaged over the entire cohort. After the conclusion of the study, approximately one-half of the parents believed that their children had benefitted from the folinic acid therapy and elected to continue treatment. Thus far, no significant side effects have been noted from long-term folinic acid therapy so we are offering all Fragile X patients a 3-month trial of medication.
Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents. [2019]Fragile X syndrome (FXS) is the most common monogenic cause of inherited intellectual and developmental disabilities. Mavoglurant, a selective metabotropic glutamate receptor subtype-5 antagonist, has shown positive neuronal and behavioral effects in preclinical studies, but failed to demonstrate any behavioral benefits in two 12-week, randomized, placebo-controlled, double-blind, phase IIb studies in adults and adolescents with FXS. Here we report the long-term safety (primary endpoint) and efficacy (secondary endpoint) results of the open-label extensions. Adolescent (n = 119, aged 12-19 years) and adult (n = 148, aged 18-45 years) participants received up to 100 mg bid mavoglurant for up to 34 months. Both extension studies were terminated prematurely due to lack of proven efficacy in the core studies. Mavoglurant was well tolerated with no new safety signal. Five percent of adults and 16.9 percent of adolescents discontinued treatment due to adverse events. Gradual and consistent behavioral improvements as measured by the ABC-CFX scale were observed, which were numerically superior to those seen in the placebo arm of the core studies. These two extension studies confirm the long-term safety of mavoglurant in FXS, but further investigations are required to determine whether and under which conditions the significant preclinical results obtained with mGluR5 inhibition can translate to humans.
Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study. [2018]A phase II randomized, placebo-controlled, double-blind study and subsequent open-label extension study evaluated the efficacy, safety, and tolerability of mavoglurant (AFQ056), a selective metabotropic glutamate receptor subtype-5 antagonist, in treating behavioral symptoms in adolescent patients with fragile X syndrome (FXS). A novel method was applied to analyze changes in symptom domains in patients with FXS using the narratives associated with the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale.