2.1 Primary The primary objective of the study is to evaluate the efficacy of troriluzole as adjunctive therapy compared to placebo in subjects with OCD who have had an inadequate response to their current OCD treatment based on the change in their…
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Source
Brief title
Condition
- Psychiatric and behavioural symptoms NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Improvement in obsessive-compulsive symptomatology is assessed using the Y-BOCS
change from baseline in the total score.
Secondary outcome
• Safety and tolerability are assessed using the frequency of unique subjects
with: SAEs; AEs leading to discontinuation; AEs judged to be related to study
medication; and clinically significant laboratory abnormalities that are
observed during the double-blind phase;
• Improvement in functional disability is assessed using the change in the
Sheehan Disability Scale (SDS) total score from baseline;
• Improvement in global clinical condition is assessed using the change in the
CGI-S score from baseline
Background summary
Biohaven Pharmaceuticals, Inc. is developing a new drug, troriluzole, for the
treatment of Obsessive-Compulsive Disorder (OCD) as well as for other
neurologic and psychiatric disorders. Troriluzole is a tripeptide prodrug of
the glutamate modulating agent riluzole that has been optimized for improved
bioavailability, pharmacokinetics and dosing. The proposed study in OCD is
based on recent preclinical, clinical and neuroimaging studies that implicate
glutamatergic hyperactivity in the pathogenesis of OCD. Additionally,
preliminary efficacy findings from BHV4157-202, a proof-of-concept study,
indicate, troriluzole 200 mg, administered once daily as adjunctive therapy in
subjects with OCD who had an inadequate response to SOC treatment showed
numerically greater improvement versus placebo in the total Y-BOCS score in the
randomization phase. Biohaven hypothesizes that the pleiotropic effects of
riluzole (e.g., glutamate modulation) may target mechanisms underlying
pathologic brain function that is associated with OCD, and thus provide
symptomatic benefit in patients suffering from Obsessive Compulsive Disorder
(OCD).
The proposed study is based on recent preclinical, clinical, genetic and
neuroimaging studies that implicate glutamatergic hyperactivity in the
pathogenesis of OCD. In multiple published clinical case studies, the use of
agents that modulate brain glutamate have been suggested to have efficacy in
patients with refractory OCD.
Study objective
2.1 Primary
The primary objective of the study is to evaluate the efficacy of troriluzole
as adjunctive therapy compared to placebo in subjects with OCD who have had an
inadequate response to their current OCD treatment based on the change in their
Y-BOCS score.
2.2 Secondary
• To assess the safety and tolerability of troriluzole, relative to placebo, in
subjects with OCD;
• Evaluate the efficacy of troriluzole compared to placebo on functional
disability as measured by the Sheehan Disability Scale (SDS);
• Evaluate the efficacy of troriluzole compared to placebo on global clinical
condition as measured by the Clinical Global Impression- Severity Scale
(CGI-S);
Study design
BHV4157-303 is a Phase III, multicenter, randomized, double-blind, 2-arm
placebo- controlled parallel-group study designed to assess safety,
tolerability, and efficacy of troriluzole as adjunctive therapy in a population
of subjects with OCD who have had an inadequate response to standard of care
treatment.
The expected duration of study participation for each subject is up to 18
weeks, including:
• Screening phase up to 6 weeks
• Treatment period 10 weeks
Post-treatment safety period: subjects will have a follow-up safety visit two
weeks after discontinuing study drug or if eligible, will participate in the
Open Label Extension Study, BHV4157-209
Intervention
Subjects who are stable on SOC medication and having an inadequate response (as
defined above) will be randomized to additionally receive placebo (QD) or
troriluzole in ration 1:1. Subjects will receive either placebo or troriluzole
200mg for the first two weeks and then will be increased to 280 mg (or matching
placebo) for the duration of the study.
Study burden and risks
Analysis of the available data with troriluzole from in-vitro studies,
preclinical studies (in rats and monkeys), and clinical studies in healthy
subjects as well as patients with OCD, GAD, SCA, and AD, supports a favorable
benefit-risk profile. Therefore, it is considered that the benefits of
evaluating troriluzole as a potential treatment for OCD outweigh the risks.
Haros Str 103
Budapest 1222
NL
Haros Str 103
Budapest 1222
NL
Listed location countries
Age
Inclusion criteria
1.Primary diagnosis of OCD as per Diagnostic and Statistical Manual of Mental
Disorders, Fifth Edition as confirmed by the MINI at Screening; The duration of
the subject's illness must be >= 1 year;
2.Subjects must be currently experiencing non-response or inadequate response
to their current SOC medication defined as: Subjects Y-BOCS total score must be
>= 22 at Screening and Baseline, reflecting moderate or severe OCD symptoms.
3.Subjects must currently be on an SSRI (with the exception of fluvoxamine, see
Section 1.1.3), or clomipramine, venlafaxine or desvenlafaxine monotherapy
treatment for an adequate duration and at an adequate dose defined as in
clinical trial protocol
4.Subjects must be on stable doses of other psychotropic medication (with
exclusions specified below) for at least 12 weeks prior to screening;
5.CGI-S score of >= 4 at screening and baseline;
6.Women of child bearing potential (WOCBP) and fertile men (including those
vasectomized for less than 6 months) with female partners whoare WOCBP (not
having undergone bilateral tubal occlusion procedure and not postmenopausal)
must agree to use highly effective birth control, including two methods of
contraception, for the duration of the study (i.e., beginning 30 days prior to
Baseline and extending to 30 days for women and 90 days for men after the last
dose of study drug). The
two methods of contraception should include:
i.One barrier method (e.g. diaphragm with spermicide, condom with spermicidal
gel, cervical cap)*
ii.One other method that could include hormonal contraceptives (e.g. combined
estrogen and progesterone containing, or progesterone only with oral, vaginal,
injectable, or transdermal route of administration), intrauterine device, or
intrauterine hormone releasing system used for at least 4 weeks prior to sexual
intercourse
7.WOCBP must have a negative serum pregnancy test at screening and a negative
urine pregnancy test within approximately 24 hours prior to dosing at Baseline
8.It is required that men who are sexually active with WOCBP agree to use two
methods of contraception for the duration of the study (beginning at first
treatment and extending to 90 days after the last dose of study drug).
Exclusion criteria
1.Subjects with a history of more than two (2) previous failed or inadequate
treatment classes SSRIs, clomipramine, venlafaxine, or desvenlafaxine, given
for an adequate duration at an adequate dose as defined by the criteria taken
from the MGH-TRQ-OCD .
2.Subjects should be excluded at screening or baseline if any medical or
psychiatric condition other than OCD, as specified in the inclusion criteria,
could predominantly explain or contribute significantly to the subjects'
symptoms or that could confound assessment of OCD symptoms;
3.Current or prior history, per DSM-5 criteria, of bipolar I or II disorder,
schizophrenia or other psychotic disorders, schizoaffective disorder, autism or
autistic spectrum disorders, borderline personality disorder, antisocial
personality disorder, body dysmorphic disorder, hoarding disorder (symptoms of
hoarding disorder as part of the OCD diagnosis are allowed, but a primary
diagnosis of hoarding disorder is excluded); a current diagnosis of Tourette's
disorder is also excluded;
4.Any eating disorder within the last 12 months;
5.Primary active major depressive episode or primary active anxiety disorder
within the past 6 months.
6.Acute suicidality or suicide attempt or self-injurious behavior in the last
12 months.
7.Any positive ("yes") C-SSRS response to questions 1-5 in last 6 months at
screening and/or Since the Last Visit (before dosing) at the baseline visit;
9.Subjects who may have received a non-biological investigational agent in any
clinical trial within 30 days or a biological agent within 90 days prior to
screening;
10.History of psychosurgery, Deep Brain Stimulation (DBS) or Electroconvulsive
Therapy (ECT).
11.History of substance use disorder (drug or alcohol) in the last 12 months,
with the exception of tobacco, as defined by DSM-5 criteria;
12.Positive urine drug screening for cannabis (both medical and recreational
use of cannabis are prohibited; subjects will be expected to refrain from use
during the period of the study), amphetamines (including MDMA/ecstasy),
cocaine, barbiturate, PCP, and/or opiates at screening.
13. Women who are pregnant or brestfeeding
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-004653-69-NL |
| ClinicalTrials.gov | NCT04693351 |
| CCMO | NL76918.018.21 |