Clinical trial NCT05085561: The Symptomatic Cerebral Cavernous Malformation Trial of REC-994
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cerebral Cavernous Malformation
Lead sponsor: Recursion Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-20
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 subjects with symptomatic cerebral cavernous malformation (CCM).


Eligibility criteria: 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)

Primary outcomes:
measure: Incidence and severity of adverse events (AEs)
timeFrame: 24 months
measure: Incidence of clinically significant changes in physical examinations
timeFrame: 12 months (Part 2)
Secondary outcomes:
measure: Change in patient reported outcomes (Cerebral Cavernous Malformation Health Index)
timeFrame: 24 months
measure: Change in patient reported outcomes (Modified Rankin Scale)
timeFrame: 24 months
measure: Change in patient reported outcomes (SymptoMScreen Score)
timeFrame: 24 months
measure: Change in disease-associated symptoms (size and number of lesions on MRI)
timeFrame: 24 months
measure: Change in disease-associated symptoms (number of MRI-confirmed cerebral hemorrhagic events)
timeFrame: 24 months
measure: Incidence of clinically significant changes in physical examinations
timeFrame: 12 months (Part 1)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Xenoscience Inc
state: Arizona
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Lyerly Neurosurgery
state: Florida
city: Port Saint Lucie
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory
state: Georgia
city: Ridgewood
country: United States
facility: Valley Hospital
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
References: