The Symptomatic Cerebral Cavernous Malformation Trial of REC-994

Study Overview
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Brief Summary
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This is a two-part, multi-center, randomized, double-blind, placebo-controlled study to investigate the safety, efficacy and pharmacokinetics of REC-994 (200 mg and 400 mg) compared to placebo in subjects with symptomatic cerebral cavernous malformation (CCM).

Official Title
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A Two-Part Study of REC-994 in the Treatment of Adults With Symptomatic Cerebral Cavernous Malformation (CCM); Part 1: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Two Doses of REC-994; Part 2: A Long-Term Blinded Extension Clinical Trial to Evaluate Long-Term Safety Tolerability and Efficacy of REC-994

Conditions
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Cerebral Cavernous Malformation

Intervention / Treatment
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* Drug: REC-994
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 18 years of age or older with anatomic CCM lesions demonstrated by brain MRI Have symptomatic CCM Have provided written informed consent to participate in the study Have NOT participated in a clinical trial utilizing an investigational agent within 28 days or within 5 half-lives of the investigational drug (whichever is longer) prior to Screening Exclusion Criteria: Symptoms deemed by the study Investigator to be caused exclusively by irreversible neuronal damage from prior stroke or neurosurgical instrumentation History of cranial irradiation or surgical/radiosurgical treatment of the primary symptomatic CCM lesion Pregnant or breast feeding Be unable or unwilling to participate in MRI assessments (e.g., claustrophobia, metal implant or implanted cardiac pacemaker) Liver dysfunction or active liver disease as defined by baseline serum transaminases >2x upper limit of normal (ULN) Have moderately or severely impaired renal function (estimated glomerular filtration rate [eGFR] <60ml/min) or active renal disease or have previously received a kidney transplant Have had a previous diagnosis of skeletal muscle disorders (myopathy) of any cause or have a baseline creatine kinase level > 5x ULN History of alcohol or substance abuse within 1 year prior to screening Clinically significant laboratory abnormality Have had an intracerebral hemorrhage within 3 months of screening or any brain surgery within 6 months of screening (not including the primary symptomatic CCM lesion)

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: REC-994 200 mg<br>REC-994 200 mg po once daily (QD) (1 200 mg REC-994 tablet, 1 matching placebo tablet) | Drug: REC-994<br>* REC-994 200 mg tablets<br>Drug: Placebo<br>* Placebo Tablets<br>|
| Active Comparator: REC-994 400 mg<br>REC-994 400 mg po QD (2 200 mg REC-994 tablets) | Drug: REC-994<br>* REC-994 200 mg tablets<br>|
| Placebo Comparator: Placebo<br>Matching Placebo po QD (2 matching placebo tablets) | Drug: Placebo<br>* Placebo Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs) | Safety and tolerability | 24 months | 
| Incidence of clinically significant changes in physical examinations | Safety and tolerability | 12 months (Part 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient reported outcomes (Cerebral Cavernous Malformation Health Index) | Efficacy | 24 months | 
| Change in patient reported outcomes (Modified Rankin Scale) | Efficacy | 24 months | 
| Change in patient reported outcomes (SymptoMScreen Score) | Efficacy | 24 months | 
| Change in disease-associated symptoms (size and number of lesions on MRI) | Efficacy | 24 months | 
| Change in disease-associated symptoms (number of MRI-confirmed cerebral hemorrhagic events) | Efficacy | 24 months | 
| Incidence of clinically significant changes in physical examinations | Safety and tolerability | 12 months (Part 1) |