CLARITY: Phase IIb-III Study of BL-1020 Small Molecule for Schizophrenia

• Sponsor: BioLineRx, Ltd. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01363349
• Collaborator: (none)
• Enrollment: 269
• Locations: 39
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a randomized, double-blind, active-controlled, 6 month study designed to evaluate the cognitive effects of treatment with CYP-1020 compared to risperidone. The primary efficacy endpoint will occur after 6 weeks of treatment; additional (secondary) efficacy endpoints will occur after 12 and 24 weeks of treatment.

Up to 450 patients will be randomized to CYP-1020 or risperidone in a 1:1 ratio. The study will utilize a flexible dose escalation scheme designed to allow patients to titrate to their maximally tolerated dose; doses of CYP-1020 may range from a minimum of 15 mg to a maximum of 35 mg, whereas doses of risperidone will range from a minimum of 1 mg to 3 mg BID (2-6 mg daily). To ensure effective blinding across all treatment groups, all patients will be treated twice daily with study drug and/or placebo, as indicated (i.e., double-dummy design).

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Cognitive Effect on Schizophrenic Patients	Drug: CYP-1020; Drug: Risperidone	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 269 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Active-Controlled,Phase 2/3 Study to Determine the Short-Term (6-Week) and Long-Term (6 Month) Cognitive and Anti-Psychotic Efficacy, Safety and Tolerability of CYP-1020 Compared to Risperidone in Patients With Schizophrenia
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CYP-1020 Dose titration 15-35mg/day for 6 months	Drug: CYP-1020; CYP-1020 (formerly known as BL-1020) is an orally available new chemical entity.; Other Names: BL-1020
Active Comparator: Risperidone Dose titration 2-6mg/day for 6 months	Drug: Risperidone

Outcome Measures

Primary Outcome Measures

1. Cognition [Baseline and 6 weeks]

   To evaluate the cognitive benefits of treatment with CYP-1020 (formerly known as BL-1020) compared to risperidone after 6 weeks of treatment in patients experiencing acute exacerbation of schizophrenia. Assessed by calculating difference between CYP-1020 and Risperidone on mean change from baseline to Week 6 endpoint on MATRICS Consensus Cognition Battery (MCCB) normative composite score. MCCB is a neuropsychological test battery that comprises 10 measures of 7 different cognitive areas including speed of processing, verbal learning, memory-verbal and non verbal reasoning and problem solving, visual learning, social cognition, attention/vigilance.The study was terminated after the interim analysis. MCBB total score ranges from -50 to 150. Change from Baseline by Visit (LOCF)Higher score means better cognitive functioning.

Secondary Outcome Measures

1. Long Term Cognition [12 and 24 weeks of treatment]

   Evaluation of the cognitive benefits of treatment with BL-1020 compared to risperidone after 12 and 24 weeks of treatment

2. Long Term Schizophrenia Treatment [Baseline and 6, 12 and 24 weeks of treatment]

   Evaluation of the antipsychotic efficacy of BL-1020 compared to risperidone after 6, 12 and 24 weeks of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or non-pregnant or lactating female, 18-50 years of age inclusive

2. Patients must have exhibited symptoms meeting the criteria of schizophrenia for at least one year, but not more than 20 years, prior to Screening

3. Recent onset (not more than 30 days) of worsening of psychiatric symptoms at Screening.

4. Currently experiencing an acute exacerbation of schizophrenia, as defined by the following results at Screening and Baseline:

• ≥70 total score on the PANSS

• ≥4 (moderate) on two of the following four PANSS items: (1) delusions, (2) hallucinatory behaviors, (3) conceptual disorganization or (4) suspiciousness/persecution, where at least one of the two items must be either delusions or hallucinatory behaviors

1. CGI-S score between 4 and 6 (moderately ill to severely ill) at the Screening and Baseline visits.

2. Has exhibited a sufficient clinical response to at least one previous course of an anti-psychotic agent prescribed at a generally recognized therapeutic dose.

3. Must have completed at least 5 years of formal education or its equivalent

Exclusion Criteria:

1. Breastfeeding or pregnant

2. Symptoms of schizophrenia for more than 20 years at the time of screening.

3. Psychotic symptoms that have failed to improve (based on Investigator's opinion or documented medical history) following sufficient treatment with therapeutic doses of two or more anti-psychotics agents over the preceding 2 years

4. Prior history of neuroleptic malignant syndrome

5. Prior history or current evidence of moderate or severe tardive dyskinesia (mild is acceptable).

6. Abnormal ECG evaluation

7. History of confirmed epilepsy or prior seizure disorder (history of a single febrile seizure is not exclusionary)

8. In the opinion of the investigator, unstable medical disease (e.g., malignancy, poorly controlled diabetes or hypertension, ischemic cardiac disease, dilated cardiomyopathy or valvular heart disease, pulmonary disease, liver disease, kidney disease)

9. Acute infectious disease (e.g., malaria, dengue fever, hepatitis A), or chronic infectious disease (e.g., history of AIDS or HIV positivity, tuberculosis)

10. Likely allergy, sensitivity or intolerance to BL-1020, perphenazine, risperidone, paliperidone, or any of the drug product excipients

11. Any suicide attempt within the preceding 2 years

12. Any Substance Dependence disorder

13. High likelihood of substance abuse

14. Diagnosis with one of the following DSM-IV-TR Axis I diagnoses: schizophreniform disorder, schizoaffective disorder, bipolar disorder, substance dependency, mood disorder with psychotic features; psychotic disorder NOS

15. Requiring chronic treatment with benzodiazepines

16. Requiring chronic treatment with mood stabilizers

17. Previously treated with clozapine within 6 months prior to screening

18. Any abnormal clinical laboratory test result that is judged by the Investigator to be clinically significant

19. History of, or serologic evidence of, acute or chronic active hepatitis B or C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Psychiatry, Sheath VS General Hospital, Sheath KM School of Post Graduate Medicine & Research	Ahmedabad		India
2	Saoji Tupkari Hospital	Aurangabad		India
3	Spandana Nursing Home	Bangalore		India
4	KHM Hospital	Chennai		India
5	Asha Hospital	Hyderabad		India
6	Department of Psychiatry, Owaisi Hospital & Research Centre	Hyderabad		India
7	RK Yadav Memorial Mental Health and De-addiction Hospital	Jaipur		India
8	Mahendru Psychiatric Centre	Kanpur		India
9	Dreamland Nursing Home	Kolkata		India
10	Dayanand Medical College & Hospital	Ludhiana		India
11	Centre for Psychiatric Research, Department of Psychiatry, K.S Hegde Medical Academy	Mangalore		India
12	Jaslok Hospital&Research Centre	Mumbai		India
13	JSS Medical College Hospital	Mysore		India
14	Sujata Birla Hospital	Nashik		India
15	Vimhans Hospital	New Delhi		India
16	S.V.Medical College	Tirupati		India
17	Deva Mental Health Care	Varanasi		India
18	Vijayawada Institute of Mental Health & Neurosciences	Vijayawada		India
19	IMSP Spitalul Clinic de Psihiatrie, Sectia 14	Chisinau		Moldova, Republic of
20	IMSP Spitalul Clinic de Psihiatrie, Sectia 17	Chisinau		Moldova, Republic of
21	IMSP Spitalul Clinic de Psihiatrie, Sectia 8	Chisinau		Moldova, Republic of
22	pitalul Clinic Judetean de Urgenta Arad Clinica Psihiatrie	Arad		Romania
23	Spitalul de Psihiatrie si Neurologie Brasov	Brasov		Romania
24	Spitalul Clinic de Psihiatrie "Prof. Dr. Al. Obregia"	Bucharest		Romania
25	Spitalul Clinic de Psihiatrie Dr. Alexandru Obregia Department 13	Bucharest		Romania
26	Spitalul Clinic de Psihiatrie Dr. Alexandru Obregia Department 1	Bucharest		Romania
27	Spitalul Clinic de Psihiatrie Dr. Alexandru Obregia Department 8	Bucharest		Romania
28	Spitalul Clinic de Psihiatrie Dr. Alexandru Obregia Department 9	Bucharest		Romania
29	Spitalul de Psihiatrie C.E.T.T.T. "Sf. Stelian"	Bucharest		Romania
30	Spitalul Judetean Cluj Napoca	Cluj Napoca		Romania
31	Spitalul Clinic Judetean de Urgenta Constanţa Clinica de Psihiatrie	Constanta		Romania
32	Spitalul Clinic de Neuropsihiatrie Clinica de Psihiatrie nr. 2	Craiova		Romania
33	Spitalul de Neuropsihiatrie Clinica de Psihiatrie I	Craiova		Romania
34	Spitalul Clinic de Psihiatrie Socola	Iasi		Romania
35	Spital Clinic de Neurologie si Psihiatrie Oradea	Oradea		Romania
36	Spitalul Clinic Municipal "Dr.Gavril Curteanu" Oradea	Oradea		Romania
37	Spitalul de Psihiatrie "Dr. Gh. Preda"	Sibiu		Romania
38	Spitalul Judetean de Urgenta Targoviste Clinica Psihiatrie Adulti nr. 7	Targoviste		Romania
39	Spitalul Clinic Judetean Mures, Clinica Psihiatrie Nr. 2	Targu-Mures		Romania

Sponsors and Collaborators

• BioLineRx, Ltd.

Investigators

• Study Chair: Arnon Aharon, MD, BioLineRx, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: BioLineRx, Ltd.
• ClinicalTrials.gov Identifier: NCT01363349
• Other Study ID Numbers: 1020-CLIN-201; NCT01365299
• First Posted: Jun 1, 2011
• Last Update Posted: Sep 18, 2014
• Last Verified: Sep 1, 2014

• Additional relevant MeSH terms: Schizophrenia; Risperidone

Study Results

Participant Flow

Arm/Group Title	CYP-1020	Risperidone
Arm/Group Description	CYP-1020: CYP-1020 (formerly known as BL-1020) is an orally available new chemical entity.	2-6 mg, 6 months Risperidone
Period Title: Overall Study
STARTED	133	136
Randomized	133	136
COMPLETED	66	66
NOT COMPLETED	67	70

Baseline Characteristics

Arm/Group Title	CYP-1020	Risperidone	Total
Arm/Group Description	CYP-1020: CYP-1020 (formerly known as BL-1020) is an orally available new chemical entity.	2-6 mg, 6 months Risperidone	Total of all reporting groups
Overall Participants	133	136	269
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.3 (8.76)	32.3 (7.97)	32.8 (8.37)
Sex: Female, Male (Count of Participants)
Female	49 36.8%	49 36%	98 36.4%
Male	84 63.2%	87 64%	171 63.6%
Race/Ethnicity, Customized (number of participants) [Number]
asian	92 69.2%	94 69.1%	186 69.1%
caucasian	41 30.8%	42 30.9%	83 30.9%
Region of Enrollment (participants) [Number]
Romania	41 30.8%	42 30.9%	83 30.9%
India	92 69.2%	94 69.1%	186 69.1%

Outcome Measures

1. Primary Outcome

Title	Cognition
Description	To evaluate the cognitive benefits of treatment with CYP-1020 (formerly known as BL-1020) compared to risperidone after 6 weeks of treatment in patients experiencing acute exacerbation of schizophrenia. Assessed by calculating difference between CYP-1020 and Risperidone on mean change from baseline to Week 6 endpoint on MATRICS Consensus Cognition Battery (MCCB) normative composite score. MCCB is a neuropsychological test battery that comprises 10 measures of 7 different cognitive areas including speed of processing, verbal learning, memory-verbal and non verbal reasoning and problem solving, visual learning, social cognition, attention/vigilance.The study was terminated after the interim analysis. MCBB total score ranges from -50 to 150. Change from Baseline by Visit (LOCF)Higher score means better cognitive functioning.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Analysis for MCCB Score ITT population.

Arm/Group Title	CYP-1020	Risperidone
Arm/Group Description	CYP-1020: CYP-1020 (formerly known as BL-1020) is an orally available new chemical entity.	2-6 mg, 6 months Risperidone
Measure Participants	133	136
MCCB Baseline Score	8.7 (13.66)	8.2 (13.86)
MCCB Week 6 Score	13.5 (12.92)	12.5 (13.68)

2. Secondary Outcome

Title	Long Term Cognition
Description	Evaluation of the cognitive benefits of treatment with BL-1020 compared to risperidone after 12 and 24 weeks of treatment
Time Frame	12 and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Long Term Schizophrenia Treatment
Description	Evaluation of the antipsychotic efficacy of BL-1020 compared to risperidone after 6, 12 and 24 weeks of treatment
Time Frame	Baseline and 6, 12 and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	CYP-1020		Risperidone
Arm/Group Description	CYP-1020: CYP-1020 (formerly known as BL-1020) is an orally available new chemical entity.		2-6 mg, 6 months Risperidone
All Cause Mortality
	CYP-1020		Risperidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CYP-1020		Risperidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/133 (4.5%)		5/136 (3.7%)
Infections and infestations
pneumonia	1/133 (0.8%)	1	0/136 (0%)	0
Musculoskeletal and connective tissue disorders
muscle rigidity	1/133 (0.8%)	1	0/136 (0%)	0
Psychiatric disorders
schizophrenia	2/133 (1.5%)	2	3/136 (2.2%)	3
completed suicide	1/133 (0.8%)	1	0/136 (0%)	0
delerium	1/133 (0.8%)	1	0/136 (0%)	0
insomnia	0/133 (0%)	0	1/136 (0.7%)	1
persecutory delusion	1/133 (0.8%)	1	0/136 (0%)	0
sleep disorder	0/133 (0%)	0	1/136 (0.7%)	1
suicidal ideation	0/133 (0%)	0	1/136 (0.7%)	1
Renal and urinary disorders
pollakiuria	0/133 (0%)	0	1/136 (0.7%)	1
Other (Not Including Serious) Adverse Events
	CYP-1020		Risperidone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	105/133 (78.9%)		101/136 (74.3%)
Gastrointestinal disorders
vomiting	8/133 (6%)	8	3/136 (2.2%)	3
salivary hypersecretion	11/133 (8.3%)	11	6/136 (4.4%)	6
Infections and infestations
NASOPHARYNGITIS	9/133 (6.8%)	9	2/136 (1.5%)	2
Metabolism and nutrition disorders
DECREASED APPETITE	7/133 (5.3%)	7	3/136 (2.2%)	3
Musculoskeletal and connective tissue disorders
MUSCLE RIGIDITY	32/133 (24.1%)	32	24/136 (17.6%)	24
Nervous system disorders
TREMOR	30/133 (22.6%)	30	28/136 (20.6%)	28
AKATHISIA	18/133 (13.5%)	18	18/136 (13.2%)	18
SOMNOLENCE	11/133 (8.3%)	11	12/136 (8.8%)	12
SEDATION	8/133 (6%)	8	2/136 (1.5%)	2
Psychiatric disorders
INSOMNIA	20/133 (15%)	20	26/136 (19.1%)	26
RESTLESSNESS	11/133 (8.3%)	11	12/136 (8.8%)	12
ANXIETY	8/133 (6%)	8	9/136 (6.6%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.