Cerebral Cavernous Malformation
Conditions
Keywords
Cerebral Cavernous Malformation, CCM
Brief summary
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 participants with symptomatic cerebral cavernous malformation (CCM).
Detailed description
Part 1: Participants will receive treatment over a period of 12 months. Part 2: Optional long-term extension (LTE) for participants completing Part 1 and who are eligible for extended treatment with REC-994.
Interventions
DRUGREC-994
REC-994 200 mg tablets
DRUGPlacebo
Placebo Tablets
Sponsors
Recursion Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older with anatomic CCM lesions demonstrated by brain MRI 2. Have symptomatic CCM 3. Have provided written informed consent to participate in the study 4. 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
1. Symptoms deemed by the study Investigator to be caused exclusively by irreversible neuronal damage from prior stroke or neurosurgical instrumentation 2. History of cranial irradiation or surgical/radiosurgical treatment of the primary symptomatic CCM lesion 3. Pregnant or breast feeding 4. Be unable or unwilling to participate in MRI assessments (e.g., claustrophobia, metal implant or implanted cardiac pacemaker) 5. Liver dysfunction or active liver disease as defined by baseline serum transaminases \>2x upper limit of normal (ULN) 6. 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 7. Have had a previous diagnosis of skeletal muscle disorders (myopathy) of any cause or have a baseline creatine kinase level \> 5x ULN 8. History of alcohol or substance abuse within 1 year prior to screening 9. Clinically significant laboratory abnormality 10. 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of adverse events (AEs) | Up to 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Change in patient reported outcomes (Cerebral Cavernous Malformation Health Index) | Up to 24 months |
| Change in patient reported outcomes (Modified Rankin Scale) | Up to 24 months |
| Change in patient reported outcomes (SymptoMScreen Score) | Up to 24 months |
| Change in disease-associated symptoms (number of MRI-confirmed cerebral hemorrhagic events) | Up to 24 months |
| Plasma concentrations of REC-994 | Up to 12 months |
Countries
United States
Outcome results
None listed