The Symptomatic Cerebral Cavernous Malformation Trial of REC-994 (SYCAMORE)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Cerebral Cavernous Malformation
• Intervention / Treatment: Drug: Placebo; Drug: REC-994

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Recursion Pharmaceuticals; Phone Number: 385-374-1724; Email: clinicaltrials@recursionpharma.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience Inc
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
    • Jacksonville, Florida, United States, 32207-8202
      • Lyerly Neurosurgery
    • Port Saint Lucie, Florida, United States, 34987
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • Valley Hospital
  • New York
    • New York, New York, United States, 10027
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75390-8855
      • The University of Texas Southwestern Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Recursion Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Cardiovascular Abnormalities; Hemangioma; Neoplasms, Vascular Tissue; Nervous System Malformations; Vascular Malformations; Central Nervous System Vascular Malformations; Hemangioma, Cavernous; Congenital Abnormalities; Hemangioma, Cavernous, Central Nervous System
• Other Study ID Numbers: REC-994-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No