An adaptive, randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of RL-007 in the treatment of cognitive impairment associated with schizophrenia (CIAS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Recognify Life Sciences Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

13 Jun 2024 → 24 Apr 2025

Decision date (initial)

2024-05-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Recognify Life Sciences, Inc.

External identifiers

EU CT number

2023-506570-12-01

WHO UTN

U1111-1294-5774

ClinicalTrials.gov

NCT05686239

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the effects of RL-007 on cognitive performance in participants diagnosed with schizophrenia

Secondary objectives 2

1. To assess the safety and tolerability of RL-007 in participants diagnosed with schizophrenia
2. Other efficacy measures of interest

Conditions and MedDRA coding

Cognitive disorder

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Is an adult of any sex, gender, and race/ethnicity between 18 and 55 years of age, inclusive, at time of consent.
2. If participant is of child-bearing potential*, has a negative serum pregnancy test at screening and negative urine pregnancy test before dosing.
3. Is unable* to become pregnant or father a child, or agrees to be sexually abstinent or use a highly effective method of contraception from screening through 90 days post last dose and not to donate sperm or ovum(s) during this period. *See Appendix 1 for definition and guidance on acceptable contraception methods.
4. Diagnosis of schizophrenia, as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) with a duration of least 6 months. The diagnosis will be confirmed by utilizing the Mini International Neuropsychiatric Interview (MINI) with the Psychotic Disorders module.
5. Positive and Negative Symptoms Severity Score (PANSS) of less than or equal to 80 (inclusive), and a score of 5 or less on the following items: hallucinatory behavior (P3), grandiosity (P5), suspiciousness/persecution (P6), depression (G6) and a score of 4 or less on conceptual disorganization (P2).
6. Currently being treated with a single atypical antipsychotic* (other than clozapine) at a stable dose (defined as ±25% at least 1 month ago and no changes since) and must have been on that medication and clinically stable (defined as not requiring a change in treatment or any psychiatric care beyond regularly scheduled appointments) for at least 4 weeks before the screening visit. *Note: long-acting injectables are allowed. Participants need to be stable on a maintenance dose for at least one completed injection cycle before as per local prescribing information before screening start. Quetiapine (up to 100 mg, per night PRN), when used in addition to another antipsychotic medication is allowed when taken at least 12 hours prior to cognitive testing.
7. Modified Simpson-Angus Scale total score < 6, with all individual item scores < 3.
8. Clinical Global Impression – Severity score <5.
9. Is judged otherwise to be in good health based on medical history, physical examination, vital sign measurements, and laboratory safety tests performed at the screening visit and/or before the first dose of study drug.
10. Have a body mass index (BMI) ≤40.0 kg/m2 at the time of screening.
11. Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the Schedule of Assessments.
12. If the participant is a current smoker, they must be willing to abstain from smoking or other nicotine products for the 30 minutes prior to the cognitive testing.
13. Participant has reliable housing that is not expected to change during the study period with no expected significant life events (e.g., pending loss of housing, residential status change, travel, surgery, etc.) that could affect study outcomes throughout entire study period.
14. Sufficient fluency in the local country language to understand and complete study instructions and assessments.
15. Willing and able* to provide written informed consent. *Defined as having the legal capacity to independently sign the informed consent. Participants with a legal guardian are not eligible to enroll.

Exclusion criteria 23

1. Known sensitivity to any of the planned study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Sponsor, contraindicates participation in the study.
2. Prior exposure to RL-007
3. History of hospitalization for medical indication or psychiatric hospitalization within 3 months prior to screening.
4. Current use or within 5 half-lives or 14 days of randomization, whichever is longer, of cytochrome P450 3A4 (CYP3A4) sensitive substrates with a narrow therapeutic index (see Investigator Site File for list of applicable drugs).
5. Participants who present a serious risk of suicide, as evidenced by: •Participants who answer “yes” on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C SSRS) and meeting these criteria within the past 6 months, OR •Participants who, in the Investigator’s or medical monitor’s judgment, pose a significant suicide risk
6. Participants who present a risk of serious harm to others, as evidenced by any history within the past 2 years and any expressed homicidal ideation (with or without plan).
7. Any history of gastrointestinal (GI) surgery, or other condition, that may affect GI absorption or any history of GI bleeding or peptic ulcer.
8. Current primary diagnosis of another major psychiatric disorder (via MINI), intellectual disability, or any major neurological disease, brain injury, epilepsy, or severe brain trauma. Note: secondary diagnoses, other than affective disorders and substance abuse disorders may be discussed on a case-by-case basis with the medical monitor.
9. Evidence or history of significant cognitive impairment, other than associated with schizophrenia, that in the judgment of the Investigator or Sponsor would confound interpretation of study data or prevent safe and satisfactory completion of the study protocol.
10. Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years prior to screening.
11. History of cardiovascular, cerebrovascular, or peripheral vascular disease that in the judgement of the Investigator or Sponsor would confound interpretation of study data or prevent safe and satisfactory completion of the study protocol. Clinically significant screening values measured after 5 minutes of rest in a seated position include: a) Abnormal systolic blood pressure (<90 or >145 mmHg) b) Abnormal diastolic blood pressure (<40 or >95 mmHg) c) Abnormal respiratory rate (<10 or >22 breaths per minute)
12. Has a clinically significant history or presence of electrocardiogram (ECG) findings as judged by the Principal Investigator (PI) or designee at screening, including: a) HR <40 bpm or > 100 bpm b) Average QT interval corrected using Fridericia’s formula (QTcF) interval duration >450 ms for males and >470 ms for females c) Average QRS interval >120 ms d) Average PR interval >220 ms
13. Has clinically significant laboratory abnormalities including alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) laboratory values >2 × upper limits of normal (ULN) and 1.5 × ULN for bilirubin unless isolated Gilbert’s syndrome. Note: Laboratory screening can be repeated once, at Investigator discretion.
14. Meets criteria for moderate to severe substance/drug abuse disorder (including alcohol) per DSM-5 within the last 6 months prior to informed consent or a positive alcohol breath test or urine test for drugs of abuse at either Screening or Randomization Visits (except for benzodiazepines* taken according to prescription and as an ongoing, stable regimen). *Note: see Section 7.19 and Appendix 4 for further guidance on allowed/prohibited concomitant medications.
15. Positive serology panel (including hepatitis B surface antigen [HBsAg] and/or confirmed current hepatitis C virus [HCV] infection [positive HCV antibody confirmed with reflex HCV RNA test]) and/or positive human immunodeficiency virus (HIV) antibody/p24 antigen screen.
16. Has received treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days or 5 half-lives (whichever is longer) prior to dosing; prior participation at any time in non-invasive methodology trials in which no drugs were given is acceptable.
17. Participant has undergone electroconvulsive therapy within the past 12 months.
18. Has donated blood or plasma within 30 days prior to randomization or had a loss of whole blood of more than 500 mL within the 30 days prior to randomization, or receipt of a blood transfusion within 1 year prior to randomization.
19. Has experienced symptoms of acute illness or chronic disease within 14 days prior to screening, or any disease or condition (medical or surgical) that, by the determination of the Investigator or Sponsor, might compromise interpretation of the study data, or would place the participant at risk as a result of taking part in the study.
20. Participants with needle phobia or in whom venous access is technically difficult.
21. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the participant unsuitable for enrollment.
22. Has estimated glomerular filtration rate <90 mL/min/1.73 m2, determined by the creatinine clearance rate using the serum creatinine level and the Cockcroft-Gault formula.
23. Participants who have completed the MATRICS Consensus Cognitive Battery (MCCB) as part of another study within the 6 months prior to the Screening Visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to Week 6 in: The MATRICS Consensus Cognitive Battery (MCCB) neurocognitive composite score

Secondary endpoints 9

1. Change from baseline to Week 6 in: • The Symbol Coding task from the MCCB •The Speed of Processing domain of the MCCB • The Attention/Vigilance domain of the MCCB • The Working Memory domain of the MCCB • The Verbal Memory domain of the MCCB • The Visual Learning domain of the MCCB • The Reasoning and Problem solving domain of the MCCB • Clinical Global Impression – Severity (CGI-S)
2. TEAEs: From the randomization visit through the final follow up assessment on Week 8.
3. Vital signs (blood pressure, heart rate [HR], respiratory rate, and temperature): Randomization (baseline), and Weeks 3 and 6.
4. Physical examinations: Randomization (baseline) and Weeks 3 and 6.
5. ECGs: Screening (baseline) and Week 6.
6. Clinical laboratory tests [hematology, serum chemistry and urinalysis]: Randomization (baseline) and Week 6.
7. C-SSRS: Randomization (baseline) and Weeks 3 and 6.
8. Change from baseline in the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) at Week 6
9. The Social Cognition domain of the MCCB

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Recognify Life Sciences Inc.

Sponsor organisation

Recognify Life Sciences Inc.

Address

6000 Shoreline Court

City

South San Francisco

Postcode

94080-7605

Country

United States

Scientific contact point

Organisation

Recognify Life Sciences Inc.

Contact name

Ruth Milz

Public contact point

Organisation

Recognify Life Sciences Inc.

Contact name

Ruth Milz

Third parties 8

Locations

3 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications