Study to Evaluate the Effect of AFQ056 in Obsessive Compulsive Disorder (OCD) Patients Resistant to Selective Serotonin Reuptake Inhibitor (SSRI) Therapy

• ClinicalTrials.gov Identifier: NCT01813019
• Recruitment Status: Terminated
• First Posted: March 18, 2013
• Results First Posted: July 21, 2016
• Last Update Posted: January 2, 2017
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

The purpose of this study is to determine whether AFQ056 as an add on therapy to SSRIs can have beneficial effects by reducing the total score of Y-BOCS (Yale and Brown Obsessive Compulsive Scale) in OCD patients resistant to SSRI treatment (failed SSRI over 12 weeks at appropriate doses).

Condition or disease	Intervention/treatment	Phase
Patient Diagnosed With OCD and Resistant to SSRI Treatment; Failed SSRI Over 12 Weeks at Appropriate Doses	Drug: AFQ056; Drug: Placebo	Phase 2

Detailed Description:

This was a randomized, double-blind, parallel group, placebo-controlled, 12-weeks 200 mg b.i.d oral dose treatment of AFQ056 (following a 4 week up-titration period and followed by a 3 week down-titration period) or matched placebo in patients diagnosed with OCD and on background SSRI treatment for at least 12 weeks. Study was prematurely terminated at the time of the first Interim Analysis (IA) as the study did not meet its primary efficacy objective.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group Proof of Concept Study to Evaluate the Effect of AFQ056 in Obsessive Compulsive Disorder (OCD) Patients Resistant to Selective Serotonin Reuptake Inhibitor (SSRI) Therapy
• Study Start Date: November 2013
• Actual Primary Completion Date: November 2014
• Actual Study Completion Date: November 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: AFQ056; Following baseline, approximately 60 patients who are considered eligible will be randomized to AFQ056 arm and will receive the dosing regimen of 4 weeks AFQ056 b.i.d up-titration period of 50 mg,100 mg, 150 mg and 200 mg , followed by 12 weeks AFQ056 200 mg fixed dose* and then a 3 week down-titration of 100 mg, 50 mg and 25 mg AFQ056 b.i.d) *patients that do not tolerate 200 mg b.i.d may be down-titrated to 150 mg b.i.d.	Drug: AFQ056; mGluR5 antagonist; Other Name: Mavoglurant
Placebo Comparator: Placebo; Following baseline, approximately 60 patients who are considered eligible will be randomized to Placebo arm and will receive the dosing regimen of 4 weeks Placebo b.i.d up-titration period of 50 mg,100 mg, 150 mg and 200 mg , followed by 12 weeks Placebo 200 mg fixed dose* and then a 3 week down-titration of 100 mg, 50 mg and 25 mg Placebo b.i.d) *patients that do not tolerate 200 matching placebo AFQ056 mg b.i.d may be down-titrated to 150 mg b.i.d.	Drug: Placebo; Matched placebo

Outcome Measures

Primary Outcome Measures :

1. Yale - Brown Obsessive Compulsive Scale (Y-BOCS) Absolute Change From Baseline at Week 17 (End of 16-week Dosing). [ Time Frame: baseline, week 17 ]

   The Y-BOCS is a 10 item clinician-rated scale used to both determine the severity of OCD and to monitor symptom improvement throughout the course of the study. The Y-BOCS, specifically measures the severity of symptoms of OCD without being biased towards the type of obsessions or compulsions present. The scale includes questions about the amount of time spent on, how much impairment or distress experienced from, and how much resistance and control over these obsessive thoughts and compulsions. Each item is rated from 0 ("no symptoms") to 4 ("extreme symptoms") and yields a total possible score range from 0 to 40, with the following ranges indicating degree of severity:

   0-7 = sub-clinical 8-15 = mild 16-23 = moderate 24-31 = severe 32-40 = extreme Baseline was compared to week 17 (end of week 16 dosing) to produce an absolute change.

Secondary Outcome Measures :

1. Y-BOCS Reduction in Total Score From Baseline [ Time Frame: 16 weeks ]
   If a subject demonstrates at least 25% reduction in total Y-BOCS from Baseline then they will be classed as a responder whereas if a subject has a reduction in Y-BOCS of less than 25% then they will be categorized as a nonresponder.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male and female , non-smokers patients aged between 18 to 65 years (inclusive),
• A primary diagnosis of obsessive-compulsive disorder (OCD) as per Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR 4th ed, year 2000), as confirmed by an Independent Rater.
• Be on a stable appropriate dose of selective serotonin reuptake inhibitor (SSRI) treatment for at least 12 weeks prior to Baseline.
• Have an insufficient response to current SSRI treatment (as per Inclusion Criterion 4) and confirmed by an Independent Rater.
• Have a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) of score ≥ 16 at Screening (and confirmed by an Independent Rater).
• Patient must have their eligibility confirmed following the remote interview conducted by the Independent Rater.
• Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Exclusion Criteria:

• Diagnosis of primary OCD symptom of hoarding.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception (not including oral contraceptives) during dosing and for 30 days after last dosing of study medication.
• History of more than two unsatisfactory trials with different SSRI within a period of 2 years prior to screening (not including the current treatment with SSRI's given in an adequate dose for at least 12 weeks).
• Diagnosed with any primary DSM-IV-TR Axis I disorder other than OCD (as confirmed by an Independent Rater); with the exception of depression.
• History of eating disorder (e.g. anorexia, bulimia) according to DSMIV within the last 6 months prior to Screening, (as confirmed by an Independent Rater).
• Diagnosed with antisocial personality disorder (DSM-IV-TR Axis II), as confirmed by an Independent Rater.
• Has current or past medical history of bipolar disorder, schizophrenia or other psychotic disorders, schizoaffective disorder, autism or autistic spectrum disorders, borderline personality disorder, within the last 6 months prior to Screening.
• Smokers (use of tobacco products in the previous 3 months).
• History of hallucinations/psychosis that would require antipsychotic treatment or DSM-IV criteria being met
• Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non- Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.

Contacts and Locations

Locations

United States, California

Novartis Investigative Site

San Diego, California, United States, 92103

United States, Massachusetts

Novartis Investigative Site

Watertown, Massachusetts, United States, 02472

United States, New York

Novartis Investigative Site

Brooklyn, New York, United States, 11229

Bulgaria

Novartis Investigative Site

Burgas, Bulgaria, 8000

Novartis Investigative Site

Pazardzhik, Bulgaria, 4400

Novartis Investigative Site

Sofia, Bulgaria, 1431

Novartis Investigative Site

Sofia, Bulgaria, 1632

Novartis Investigative Site

Varna, Bulgaria, 9020

Czech Republic

Novartis Investigative Site

Strakonice, Czech Republic, 386 29

Germany

Novartis Investigative Site

Berlin, Germany, 10117

Novartis Investigative Site

Freiburg, Germany, 79106

Novartis Investigative Site

Muenchen, Germany, 80336

Novartis Investigative Site

Nürnberg, Germany, 90419

Novartis Investigative Site

Ulm, Germany, 89081

Switzerland

Novartis Investigative Site

Bern, Switzerland, 3010

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rutrick D, Stein DJ, Subramanian G, Smith B, Fava M, Hasler G, Cha JH, Gasparini F, Donchev T, Ocwieja M, Johns D, Gomez-Mancilla B. Mavoglurant Augmentation in OCD Patients Resistant to Selective Serotonin Reuptake Inhibitors: A Proof-of-Concept, Randomized, Placebo-Controlled, Phase 2 Study. Adv Ther. 2017 Feb;34(2):524-541. doi: 10.1007/s12325-016-0468-5. Epub 2017 Jan 2.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01813019
• Other Study ID Numbers: CAFQ056A2225
• First Posted: March 18, 2013
• Results First Posted: July 21, 2016
• Last Update Posted: January 2, 2017
• Last Verified: November 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Obsessive compulsive disorder (OCD), obsessive fears, obsessions,; compulsions, OCD SSRI resistant

Additional relevant MeSH terms:

Compulsive Personality Disorder; Obsessive-Compulsive Disorder; Personality Disorders; Mental Disorders; Anxiety Disorders