Evaluation of RL-007 on Cognitive Impairment in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study

Trial ID: 2023-506570-12-01
Protocol: C07-03-02
Sponsor: Recognify Life Sciences Inc.

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Diseases & Conditions

Cognitive disorder Schizophrenia

Objectives

The primary objective of this study is to evaluate the effects of **RL-007** on cognitive performance in participants diagnosed with **schizophrenia**. This is clinically relevant as cognitive impairment is a significant challenge in schizophrenia, affecting patients' daily functioning and quality of life. By assessing the impact of RL-007, the study aims to explore potential therapeutic benefits for cognitive enhancement in this population.

Secondary objectives include:

Assessing the safety and tolerability of RL-007 in participants diagnosed with schizophrenia, which is crucial for determining the risk-benefit profile of the treatment.
Evaluating other efficacy measures of interest, which may provide additional insights into the therapeutic potential of RL-007 beyond cognitive performance.

Participants

The clinical trial involves a total of **70 participants** diagnosed with **schizophrenia**, aiming to assess the effects of RL-007 on cognitive performance. The study population includes adults of any sex, gender, and race/ethnicity, aged between 18 and 55 years. Participants are required to have a body mass index (BMI) of 40.0 kg/m² or less and must be in generally good health, as determined by medical history, physical examination, and laboratory tests. Both male and female subjects are included, and the trial does not involve a vulnerable population. Participants must be stable on a single atypical antipsychotic medication, excluding clozapine, and must have been clinically stable for at least four weeks prior to screening. Lifestyle considerations include the requirement for smokers to abstain from nicotine products 30 minutes before cognitive testing. Participants must have reliable housing and no significant life events expected during the study period. The trial population was selected based on these criteria to ensure the reliability and validity of the study outcomes.

Plans and Procedures

The clinical trial is designed to evaluate the **safety** and **efficacy** of RL-007 in the treatment of cognitive impairment associated with **schizophrenia**. This study is an adaptive, randomized, placebo-controlled, double-blind trial. Participants will be randomly assigned to receive either RL-007 or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the double-blind nature of the study. The trial is expected to last approximately six months, with participant involvement spanning this duration.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are assessed, including age, body mass index, and health status. Participants must be adults aged 18 to 55 years, with a confirmed diagnosis of schizophrenia as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Following successful screening, participants will undergo randomization and baseline assessments, including the MATRICS Consensus Cognitive Battery (MCCB) to establish cognitive performance baselines.

Subsequent follow-up visits are scheduled at Weeks 3 and 6, during which various assessments will be conducted. These include vital signs, physical examinations, electrocardiograms (ECGs), and clinical laboratory tests. The primary endpoint is the change from baseline to Week 6 in the MCCB neurocognitive composite score. Secondary endpoints include changes in specific cognitive domains and the Clinical Global Impression – Severity (CGI-S) score. The end-of-study visit will occur at Week 8, where final assessments and evaluations will be completed.

Participants are expected to remain in the study for the entire duration unless specific conditions necessitate early termination. These conditions include significant adverse events, non-compliance with study protocols, or withdrawal of consent. The trial aims to provide comprehensive data on the potential benefits of RL-007 in improving cognitive function in individuals with schizophrenia, contributing valuable insights into the management of cognitive disorders associated with this condition.

Treatment

The clinical trial involves the administration of **RL-007**, an investigational medication, in the form of **capsules**. The active substance in RL-007 is **(2R,3S)-2-amino-3-hydroxy-3-pyridin-4-yl-1-pyrrolidin-1-ylpropan-1-one (2R,3R)-2,3-dihydroxybutanedioic acid**, which is of chemical origin. The medication is designed as a **procognitive neuromodulator** and is intended for oral use. The maximum daily dose of RL-007 is 120 mg, with a total maximum dose of 5040 mg over a treatment period of up to 6 weeks. The administration schedule and participant compliance are monitored throughout the study to ensure adherence to the dosing regimen.

The study also includes a **placebo** control, which is designed to match the RL-007 capsules in appearance but contains no active pharmaceutical ingredient. The placebo is administered orally, following the same schedule as the experimental medication, to maintain the double-blind nature of the trial. The use of a placebo allows for the assessment of RL-007's efficacy and safety in comparison to a non-active treatment, ensuring that any observed effects can be attributed to the investigational drug rather than external factors.

Efficacy

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the impact of RL-007 on cognitive impairment associated with schizophrenia. The primary endpoint is the change from baseline to Week 6 in the MATRICS Consensus Cognitive Battery (MCCB) neurocognitive composite score. This endpoint will provide a comprehensive measure of cognitive performance improvements in participants.

Secondary endpoints include changes from baseline to Week 6 in various domains of the MCCB, such as the Symbol Coding task, Speed of Processing, Attention/Vigilance, Working Memory, Verbal Memory, Visual Learning, and Reasoning and Problem Solving. Additionally, the Clinical Global Impression – Severity (CGI-S) score will be evaluated. Other assessments include the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) and the Social Cognition domain of the MCCB. These assessments will be conducted at specified timepoints, including baseline, Week 3, and Week 6, to monitor progress and efficacy.

Data collection will involve validated scales and tools, ensuring the reliability and accuracy of the efficacy assessments. The trial will also monitor treatment-emergent adverse events (TEAEs) from the randomization visit through the final follow-up assessment at Week 8, alongside vital signs, physical examinations, ECGs, and clinical laboratory tests at designated intervals. This comprehensive approach will facilitate a thorough evaluation of RL-007's efficacy in improving cognitive function in participants with schizophrenia.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Is an adult of any sex, gender, and race/ethnicity between 18 and 55 years of age, inclusive, at time of consent.
If participant is of child-bearing potential*, has a negative serum pregnancy test at screening and negative urine pregnancy test before dosing.
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.
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.
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).
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.
Modified Simpson-Angus Scale total score < 6, with all individual item scores < 3.
Clinical Global Impression – Severity score <5.
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.
Have a body mass index (BMI) ≤40.0 kg/m2 at the time of screening.
Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the Schedule of Assessments.
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.
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.
Sufficient fluency in the local country language to understand and complete study instructions and assessments.
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.

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Exclusion Criteria

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.
Prior exposure to RL-007
History of hospitalization for medical indication or psychiatric hospitalization within 3 months prior to screening.
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).
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
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).
Any history of gastrointestinal (GI) surgery, or other condition, that may affect GI absorption or any history of GI bleeding or peptic ulcer.
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.
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.
Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years prior to screening.
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)
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
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.
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.
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.
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.
Participant has undergone electroconvulsive therapy within the past 12 months.
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.
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.
Participants with needle phobia or in whom venous access is technically difficult.
Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the participant unsuitable for enrollment.
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.
Participants who have completed the MATRICS Consensus Cognitive Battery (MCCB) as part of another study within the 6 months prior to the Screening Visit.