The Symptomatic Cerebral Cavernous Malformation Trial of REC-994

Cerebral Cavernous Malformation Clinical Trial

— SYCAMORE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05085561
• Other study ID #: REC-994-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 17, 2022
• Est. completion date: December 2025

Study information

• Verified date: July 2023
• Source: Recursion Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cerebral Cavernous Malformation
• Congenital Abnormalities

Intervention

Drug:
• REC-994
REC-994 200 mg tablets
• Placebo
Placebo Tablets

Locations

Country	Name	City	State
United States	Emory	Atlanta	Georgia
United States	University of Virginia	Charlottesville	Virginia
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Florida	Gainesville	Florida
United States	Lyerly Neurosurgery	Jacksonville	Florida
United States	UCLA	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Stanford University	Palo Alto	California
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Xenoscience Inc	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Cleveland Clinic Florida	Port Saint Lucie	Florida
United States	Valley Hospital	Ridgewood	New Jersey
United States	University of Rochester Medical Center	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Recursion Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events (AEs)	Safety and tolerability	24 months
Primary	Incidence of clinically significant changes in physical examinations	Safety and tolerability	12 months (Part 2)
Secondary	Change in patient reported outcomes (Cerebral Cavernous Malformation Health Index)	Efficacy	24 months
Secondary	Change in patient reported outcomes (Modified Rankin Scale)	Efficacy	24 months
Secondary	Change in patient reported outcomes (SymptoMScreen Score)	Efficacy	24 months
Secondary	Change in disease-associated symptoms (size and number of lesions on MRI)	Efficacy	24 months
Secondary	Change in disease-associated symptoms (number of MRI-confirmed cerebral hemorrhagic events)	Efficacy	24 months
Secondary	Incidence of clinically significant changes in physical examinations	Safety and tolerability	12 months (Part 1)