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

• ClinicalTrials.gov Identifier: NCT05085561
• Recruitment Status: Active, not recruiting
• First Posted: October 20, 2021
• Last Update Posted: July 20, 2023
• Sponsor: Recursion Pharmaceuticals Inc.
• Information provided by (Responsible Party): Recursion Pharmaceuticals Inc.

Tracking Information

• First Submitted Date: October 8, 2021
• First Posted Date: October 20, 2021
• Last Update Posted Date: July 20, 2023
• Actual Study Start Date: March 17, 2022
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 13, 2023)

• Incidence and severity of adverse events (AEs) [ Time Frame: 24 months ]
  Safety and tolerability
• Incidence of clinically significant changes in physical examinations [ Time Frame: 12 months (Part 2) ]
  Safety and tolerability

Original Primary Outcome Measures (submitted: October 8, 2021)

• Incidence and severity of adverse events (AEs) [ Time Frame: 12 months ]
  Safety and tolerability
• Incidence of clinically significant changes in laboratory assessments (hematology, chemistry, coagulation, and urinalysis), 12-lead ECGs, vital sign measurements, and physical examinations. [ Time Frame: 12 months ]
  Safety and tolerability

Current Secondary Outcome Measures (submitted: June 13, 2023)

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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Cerebral Cavernous Malformation

Intervention

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

Study Arms

• Active Comparator: REC-994 200 mg
  REC-994 200 mg po once daily (QD) (1 200 mg REC-994 tablet, 1 matching placebo tablet)
  Interventions:

  • Drug: REC-994
  • Drug: Placebo
• Active Comparator: REC-994 400 mg
  REC-994 400 mg po QD (2 200 mg REC-994 tablets)
  Intervention: Drug: REC-994
• Placebo Comparator: Placebo
  Matching Placebo po QD (2 matching placebo tablets)
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 18, 2023): 62
• Original Estimated Enrollment (submitted: October 8, 2021): 60
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05085561
• Other Study ID Numbers: REC-994-201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Recursion Pharmaceuticals Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Recursion Pharmaceuticals Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Recursion Pharmaceuticals Inc.
• Verification Date: July 2023