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

Primary Purpose

Patient Diagnosed With OCD and Resistant to SSRI Treatment, Failed SSRI Over 12 Weeks at Appropriate Doses

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AFQ056
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Patient Diagnosed With OCD and Resistant to SSRI Treatment focused on measuring Obsessive compulsive disorder (OCD), obsessive fears, obsessions,, compulsions, OCD SSRI resistant

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AFQ056

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Yale - Brown Obsessive Compulsive Scale (Y-BOCS) Absolute Change From Baseline at Week 17 (End of 16-week Dosing).
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

Y-BOCS Reduction in Total Score From Baseline
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.

Full Information

First Posted
March 14, 2013
Last Updated
November 15, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01813019
Brief Title
Study to Evaluate the Effect of AFQ056 in Obsessive Compulsive Disorder (OCD) Patients Resistant to Selective Serotonin Reuptake Inhibitor (SSRI) Therapy
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 Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Terminated
Why Stopped
Study was prematurely terminated at the time of the first Interim Analysis (IA) as the study did not meet its primary efficacy objective.
Study Start Date
November 2013 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patient Diagnosed With OCD and Resistant to SSRI Treatment, Failed SSRI Over 12 Weeks at Appropriate Doses
Keywords
Obsessive compulsive disorder (OCD), obsessive fears, obsessions,, compulsions, OCD SSRI resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AFQ056
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AFQ056
Other Intervention Name(s)
Mavoglurant
Intervention Description
mGluR5 antagonist
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo
Primary Outcome Measure Information:
Title
Yale - Brown Obsessive Compulsive Scale (Y-BOCS) Absolute Change From Baseline at Week 17 (End of 16-week Dosing).
Description
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.
Time Frame
baseline, week 17
Secondary Outcome Measure Information:
Title
Y-BOCS Reduction in Total Score From Baseline
Description
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.
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Novartis Investigative Site
City
Watertown
State/Province
Massachusetts
ZIP/Postal Code
02472
Country
United States
Facility Name
Novartis Investigative Site
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11229
Country
United States
Facility Name
Novartis Investigative Site
City
Burgas
ZIP/Postal Code
8000
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Pazardzhik
ZIP/Postal Code
4400
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Sofia
ZIP/Postal Code
1632
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Varna
ZIP/Postal Code
9020
Country
Bulgaria
Facility Name
Novartis Investigative Site
City
Strakonice
ZIP/Postal Code
386 29
Country
Czech Republic
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
80336
Country
Germany
Facility Name
Novartis Investigative Site
City
Nürnberg
ZIP/Postal Code
90419
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Novartis Investigative Site
City
Bern
ZIP/Postal Code
3010
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
28044255
Citation
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.
Results Reference
derived

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

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