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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01813019
• Collaborator: (none)
• Enrollment: 50
• Locations: 15
• Arms: 2
• Duration (Months): 12
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.3

Study Details

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
• 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: Nov 1, 2013
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Nov 1, 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 Names: 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). [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	San Diego	California	United States	92103
2	Novartis Investigative Site	Watertown	Massachusetts	United States	02472
3	Novartis Investigative Site	Brooklyn	New York	United States	11229
4	Novartis Investigative Site	Burgas		Bulgaria	8000
5	Novartis Investigative Site	Pazardzhik		Bulgaria	4400
6	Novartis Investigative Site	Sofia		Bulgaria	1431
7	Novartis Investigative Site	Sofia		Bulgaria	1632
8	Novartis Investigative Site	Varna		Bulgaria	9020
9	Novartis Investigative Site	Strakonice		Czech Republic	386 29
10	Novartis Investigative Site	Berlin		Germany	10117
11	Novartis Investigative Site	Freiburg		Germany	79106
12	Novartis Investigative Site	Muenchen		Germany	80336
13	Novartis Investigative Site	Nürnberg		Germany	90419
14	Novartis Investigative Site	Ulm		Germany	89081
15	Novartis Investigative Site	Bern		Switzerland	3010

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01813019
• Other Study ID Numbers: CAFQ056A2225
• First Posted: Mar 18, 2013
• Last Update Posted: Jan 2, 2017
• Last Verified: Nov 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Obsessive compulsive disorder (OCD), obsessive fears, obsessions,; compulsions, OCD SSRI resistant
• Additional relevant MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder

Study Results

Participant Flow

Arm/Group Title	Placebo	AFQ056
Arm/Group Description	Matching Placebo b.i.d. dosing	AFQ056 b.i.d up-titration of 50mg,100mg, 150mg and 200 mg for 4 weeks then AFQ056 200mg b.i.d for 12 weeks and then a down-titration of AFQ056 100mg, 50mg and 25mg b.i.d for 3 weeks
Period Title: Overall Study
STARTED	24	26
COMPLETED	17	20
NOT COMPLETED	7	6

Baseline Characteristics

Arm/Group Title	Placebo	AFQ056	Total
Arm/Group Description	Matching Placebo b.i.d. dosing	AFQ056 b.i.d up-titration of 50mg,100mg, 150mg and 200 mg for 4 weeks then AFQ056 200mg b.i.d for 12 weeks and then a down-titration of AFQ056 100mg, 50mg and 25mg b.i.d for 3 weeks	Total of all reporting groups
Overall Participants	24	26	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.9 (10.06)	41.3 (13.27)	40.6 (11.74)
Gender (Count of Participants)
Female	13 54.2%	13 50%	26 52%
Male	11 45.8%	13 50%	24 48%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Pharmacodynamics (PD) analysis set only participants that were analyzed at baseline and Week 17. Positive change from baseline indicates a decrease in symptom severity

Arm/Group Title	Placebo	AFQ056
Arm/Group Description	Matching Placebo b.i.d. dosing	AFQ056 b.i.d up-titration of 50mg,100mg, 150mg and 200 mg for 4 weeks then AFQ056 200mg b.i.d for 12 weeks and then a down-titration of AFQ056 100mg, 50mg and 25mg b.i.d for 3 weeks
Measure Participants	17	21
Least Squares Mean (Standard Error) [Scores on a scale]	-8.0 (1.78)	-6.9 (1.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, AFQ056
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.671
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The study was terminated due to an interim analysis of the primary efficacy outcome. Study was prematurely terminated at the time of the first Interim Analysis (IA) as the study did not meet its primary efficacy objective therefore secondary objective was not measured.

Arm/Group Title	Placebo	AFQ056
Arm/Group Description	Matching Placebo b.i.d. dosing	AFQ056 b.i.d up-titration of 50mg,100mg, 150mg and 200 mg for 4 weeks then AFQ056 200mg b.i.d for 12 weeks and then a down-titration of AFQ056 100mg, 50mg and 25mg b.i.d for 3 weeks
Measure Participants	0	0

Adverse Events

Arm/Group Title	Placebo		AFQ056
Arm/Group Description	Matching Placebo b.i.d. dosing		AFQ056 b.i.d up-titration of 50mg,100mg, 150mg and 200 mg for 4 weeks then AFQ056 200mg b.i.d for 12 weeks and then a down-titration of AFQ056 100mg, 50mg and 25mg b.i.d for 3 weeks
All Cause Mortality
	Placebo		AFQ056
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		AFQ056
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/24 (8.3%)		1/26 (3.8%)
Cardiac disorders
Atrial fibrillation	1/24 (4.2%)		0/26 (0%)
Infections and infestations
Otitis media	0/24 (0%)		1/26 (3.8%)
Injury, poisoning and procedural complications
Face injury	1/24 (4.2%)		0/26 (0%)
Head injury	1/24 (4.2%)		0/26 (0%)
Limb injury	1/24 (4.2%)		0/26 (0%)
Nervous system disorders
VIIth nerve paralysis	0/24 (0%)		1/26 (3.8%)
Other (Not Including Serious) Adverse Events
	Placebo		AFQ056
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/24 (62.5%)		18/26 (69.2%)
Cardiac disorders
Bradycardia	2/24 (8.3%)		0/26 (0%)
Ear and labyrinth disorders
Vertigo	1/24 (4.2%)		2/26 (7.7%)
Gastrointestinal disorders
Abdominal pain upper	1/24 (4.2%)		2/26 (7.7%)
Dyspepsia	0/24 (0%)		2/26 (7.7%)
General disorders
Fatigue	1/24 (4.2%)		2/26 (7.7%)
Infections and infestations
Nasopharyngitis	4/24 (16.7%)		2/26 (7.7%)
Investigations
Aspartate aminotransferase increased	1/24 (4.2%)		2/26 (7.7%)
Musculoskeletal and connective tissue disorders
Back pain	0/24 (0%)		2/26 (7.7%)
Nervous system disorders
Disturbance in attention	0/24 (0%)		2/26 (7.7%)
Dizziness	2/24 (8.3%)		5/26 (19.2%)
Headache	8/24 (33.3%)		10/26 (38.5%)
Migraine	0/24 (0%)		2/26 (7.7%)
Psychiatric disorders
Abnormal dreams	1/24 (4.2%)		2/26 (7.7%)
Agitation	0/24 (0%)		2/26 (7.7%)
Depression	2/24 (8.3%)		1/26 (3.8%)
Insomnia	2/24 (8.3%)		6/26 (23.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.