Safety, Biomarker Study of RL-007 in Subjects With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and effects on electrical activity in the brain of an investigational drug (RL-007) for improving cognition in patients with schizophrenia

Detailed Description
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Potential participants will first be given an Informed Consent document and have the study explained to them. All patients who provide written informed consent will undergo screening to determine eligibility for the study. Patients who meet all eligibility criteria will be admitted to the clinic for 5 days / 4 nights as an in-patient. During this time, participants will be assigned to a specific dose cohort and will receive sequence that includes both placebo and RL-007. Brain activity and cognitive performance will be assessed on study days 2 and 4.

Official Title
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A Single-arm, Single-blind, Multiple Dose Study to Evaluate Safety and the Effects of RL-007 on Electroencephalograms and Event-related Potentials in Subjects With Schizophrenia

Conditions
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Cognitive Impairment, Schizophrenia

Intervention / Treatment
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* Drug: RL-007
* Drug: RL-007 Matching Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Provide a written informed consent Diagnosis of schizophrenia, as defined by DSM-5 and evaluated with the MINI Plus interview Positive and Negative Symptoms Severity Score (PANSS) of 40 - 80 (inclusive), and a score of 4 or less on the following PANSS items: P2, P3, P5, P6, G6. Currently being treated with a single protocol-allowed antipsychotic at a stable dose and clinically stable for at least 8 weeks before admission (note: allowed meds = aripiprazole, brexipiprazole, paliperidone, risperidone) Modified Simpson-Angus Scale total score <= 4 At least 1 standard deviation below normative value of total number of words recalled on the Hopkins Verbal Learning Test BMI <= 38 Key Exclusion Criteria: History of hospitalization for medical indication within 4 weeks prior to screening or psychiatric hospitalization within 3 months prior to screening Use of any other psychoactive medication known to interfere with the EEG/ERP assessments within 1 week prior to screening or during the study period. Subjects who present a serious risk of suicide Any history of GI surgery, or other condition, that may affect GI absorption or any history of GI bleeding or peptic ulcer. Evidence or history of significant cognitive impairment, other than associated with schizophrenia, that in the judgement of the Investigator would confound secondary or exploratory assessments or prevent safe and satisfactory completion of the study protocol. Moderate to severe alcohol use disorder, per DSM-5 within 3 months of admission visit. Positive alcohol breath test or urine test for drugs of abuse at either screening or admission visit. Currently smoking more than 1 pack of cigarettes a day and unable or unwilling to maintain smoking to less than 1 pack a day during in-patient portion of study. Positive test result for SARS-CoV2 prior to admission per site standards. Positive test for hepatitis B, hepatitis C or HIV Subjects whose hair type or style is likely to interfere with successful application of scalp electrodes. Subjects with needle phobia or in whom venous access is technically difficult. Other unspecified reasons that, in the opinion of the PI or sponsor, make the subject unsuitable for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Four dose cohorts will be enrolled sequentially.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-escalation - RL-007<br>Each cohort will include a single dose-strength. Within each cohort, the sequence of active capsules and matching placebo capsules will be varied and unknown to the participant. | Drug: RL-007<br>* Cohorts are 10 mg, 20 mg, 40 mg, and 80 mg with TID dosing<br>|
| Placebo Comparator: Dose-escalation - matching Placebo<br>Within each cohort, the sequence of active capsules and matching placebo capsules will be varied and unknown to the participant. | Drug: RL-007 Matching Placebo<br>* Cohorts are 10 mg, 20 mg, 40 mg, and 80 mg with TID dosing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-emergent Adverse Events (TEAE) | Comparison of AE rates between active and placebo dosing | Study Day 8. | 
| Change in blood pressure (systolic and diastolic) from baseline | blood pressure measured in mmHg; baseline = Day -1 | Study Day 4 | 
| Change in heart rate from baseline | heart rate measured in beats per minute; baseline = Day -1 | Study Day 4 | 
| Change in respiratory rate from baseline | respiratory rate measured in breaths per minute; baseline = Day -1 | Study Day 4 | 
| Change in temperature from baseline | temperature measured in degrees Celsius; baseline = Day -1 | Study Day 4 | 
| Change in electrocardiogram (ECG) from baseline | overall physician interpretation of ECG reading; baseline = Day -1 | Study Day 3 | 
| Change in the Columbia Suicide Severity Rating Scale (C-SSRS) from baseline | The C-SSRS assesses suicidal ideation and behavior; baseline = Day -1 | Study Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in quantitative electroencephalogram (qEEG) | change from baseline in amplitude across qEEG frequency bands (alpha, beta, delta, theta, and gamma) | Study Day 4 | 
| Change from baseline in evoked response potential (ERP) amplitude | Change from baseline in signal amplitude of the two-stimulus auditory oddball ERP | Study Day 4 | 
| Change from baseline in evoked response potential (ERP) latency | Change from baseline in signal latency of the two-stimulus auditory oddball ERP | Study Day 4 | 
| Change from baseline in amplitude of mismatch negativity (MMN) ERP | Change from baseline in signal amplitude of the MMN ERP | Study Day 4 | 
| Change from baseline in latency of mismatch negativity (MMN) ERP | Change from baseline in signal latency of the MMN ERP | Study Day 4 |