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

Recursion Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Cerebral Cavernous Malformation

Treatments: Drug: REC-994; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05085561

REC-994-201

Details and patient eligibility

About

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).

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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62 participants in 3 patient groups, including a placebo group

REC-994 200 mg

Active Comparator group

Description:

REC-994 200 mg po once daily (QD) (1 200 mg REC-994 tablet, 1 matching placebo tablet)

Treatment:

Drug: Placebo

Drug: REC-994

REC-994 400 mg

Active Comparator group

Description:

REC-994 400 mg po QD (2 200 mg REC-994 tablets)

Treatment:

Drug: REC-994

Placebo

Placebo Comparator group

Description:

Matching Placebo po QD (2 matching placebo tablets)

Treatment:

Drug: Placebo