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

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

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).

Study Overview

• Status: Terminated
• Conditions: Schizophrenia; Cognitive Effect on Schizophrenic Patients
• Intervention / Treatment: Drug: Risperidone; Drug: CYP-1020

• Study Type: Interventional
• Enrollment (Actual): 269
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Ahmedabad, India
    • Department of Psychiatry, Sheath VS General Hospital, Sheath KM School of Post Graduate Medicine & Research
  • Aurangabad, India
    • Saoji Tupkari Hospital
  • Bangalore, India
    • Spandana Nursing Home
  • Chennai, India
    • KHM Hospital
  • Hyderabad, India
    • Asha hospital
  • Hyderabad, India
    • Department of Psychiatry, Owaisi Hospital & Research Centre
  • Jaipur, India
    • RK Yadav Memorial Mental Health and De-addiction Hospital
  • Kanpur, India
    • Mahendru Psychiatric Centre
  • Kolkata, India
    • Dreamland Nursing Home
  • Ludhiana, India
    • Dayanand Medical College & Hospital
  • Mangalore, India
    • Centre for Psychiatric Research, Department of Psychiatry, K.S Hegde Medical Academy
  • Mumbai, India
    • Jaslok Hospital&Research Centre
  • Mysore, India
    • JSS Medical College Hospital
  • Nashik, India
    • Sujata Birla Hospital
  • New Delhi, India
    • Vimhans Hospital
  • Tirupati, India
    • S.V.Medical College
  • Varanasi, India
    • Deva Mental Health Care
  • Vijayawada, India
    • Vijayawada Institute of Mental Health & Neurosciences
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • IMSP Spitalul Clinic de Psihiatrie, Sectia 14
  • Chisinau, Moldova, Republic of
    • IMSP Spitalul Clinic de Psihiatrie, Sectia 17
  • Chisinau, Moldova, Republic of
    • IMSP Spitalul Clinic de Psihiatrie, Sectia 8
• Romania
  • Arad, Romania
    • pitalul Clinic Judetean de Urgenta Arad Clinica Psihiatrie
  • Brasov, Romania
    • Spitalul de Psihiatrie și Neurologie Brașov
  • Bucharest, Romania
    • Spitalul Clinic de Psihiatrie "Prof. Dr. Al. Obregia"
  • Bucharest, Romania
    • Spitalul Clinic de Psihiatrie Dr. Alexandru Obregia Department 13
  • Bucharest, Romania
    • Spitalul Clinic de Psihiatrie Dr. Alexandru Obregia Department 1
  • Bucharest, Romania
    • Spitalul Clinic de Psihiatrie Dr. Alexandru Obregia Department 8
  • Bucharest, Romania
    • Spitalul Clinic de Psihiatrie Dr. Alexandru Obregia Department 9
  • Bucharest, Romania
    • Spitalul de Psihiatrie C.E.T.T.T. "Sf. Stelian"
  • Cluj Napoca, Romania
    • Spitalul Judetean Cluj Napoca
  • Constanta, Romania
    • Spitalul Clinic Judetean de Urgenta Constanţa Clinica de Psihiatrie
  • Craiova, Romania
    • Spitalul Clinic de Neuropsihiatrie Clinica de Psihiatrie nr. 2
  • Craiova, Romania
    • Spitalul de Neuropsihiatrie Clinica de Psihiatrie I
  • Iasi, Romania
    • Spitalul Clinic de Psihiatrie Socola
  • Oradea, Romania
    • Spital Clinic de Neurologie si Psihiatrie Oradea
  • Oradea, Romania
    • Spitalul Clinic Municipal "Dr.Gavril Curteanu" Oradea
  • Sibiu, Romania
    • Spitalul de Psihiatrie "Dr. Gh. Preda"
  • Targoviste, Romania
    • Spitalul Judetean de Urgenta Targoviste Clinica Psihiatrie Adulti nr. 7
  • Targu-Mures, Romania
    • Spitalul Clinic Judetean Mures, Clinica Psihiatrie Nr. 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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
5. CGI-S score between 4 and 6 (moderately ill to severely ill) at the Screening and Baseline visits.
6. Has exhibited a sufficient clinical response to at least one previous course of an anti-psychotic agent prescribed at a generally recognized therapeutic dose.
7. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognition	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.	Baseline and 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long Term Cognition	Evaluation of the cognitive benefits of treatment with BL-1020 compared to risperidone after 12 and 24 weeks of treatment	12 and 24 weeks of treatment
Long Term Schizophrenia Treatment	Evaluation of the antipsychotic efficacy of BL-1020 compared to risperidone after 6, 12 and 24 weeks of treatment	Baseline and 6, 12 and 24 weeks of treatment

Collaborators and Investigators

• Sponsor: BioLineRx, Ltd.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: May 30, 2011
• First Submitted That Met QC Criteria: May 31, 2011
• First Posted (Estimate): June 1, 2011

Study Record Updates

• Last Update Posted (Estimate): September 18, 2014
• Last Update Submitted That Met QC Criteria: September 17, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 1020-CLIN-201