Cerebral Cavernous MalformationPhase 2SYCAMORENCT05085561
The Symptomatic Cerebral Cavernous Malformation Trial of REC-994
A Phase 2 study testing REC-994 in people with Cerebral Cavernous Malformation, run by Recursion Pharmaceuticals Inc. at 15 sites in United States.
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 participants with symptomatic cerebral cavernous malformation (CCM). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cerebral Cavernous Malformation
- What is being tested?
- REC-994
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 15 sitesUnited States
- Study dates
- 17 Mar 2022to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older with anatomic CCM lesions demonstrated by brain MRI
- Have symptomatic CCM
- Have provided written informed consent to participate in the study
- 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
Who cannot join
- Symptoms deemed by the study Investigator to be caused exclusively by irreversible neuronal damage from prior stroke or neurosurgical instrumentation
- History of cranial irradiation or surgical/radiosurgical treatment of the primary symptomatic CCM lesion
- Pregnant or breast feeding
- Be unable or unwilling to participate in MRI assessments (e.g., claustrophobia, metal implant or implanted cardiac pacemaker)
- Liver dysfunction or active liver disease as defined by baseline serum transaminases >2x upper limit of normal (ULN)
- 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
Show all 10Show fewer
- Have had a previous diagnosis of skeletal muscle disorders (myopathy) of any cause or have a baseline creatine kinase level > 5x ULN
- History of alcohol or substance abuse within 1 year prior to screening
- Clinically significant laboratory abnormality
- 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 locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Emory
Atlanta, Georgia, 30322
University of Virginia
Charlottesville, Virginia, 22908
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390-8855
University of Florida
Gainesville, Florida, 32608
Lyerly Neurosurgery
Jacksonville, Florida, 32207-8202
UCLA
Los Angeles, California, 90095
Columbia University Medical Center
New York, New York, 10027
Stanford University
Palo Alto, California, 94304
Thomas Jefferson University
Philadelphia, Pennsylvania, 19104
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Xenoscience Inc
Phoenix, Arizona, 85004
University of Pittsburgh
Pittsburgh, Pennsylvania, 15260
Cleveland Clinic Florida
Port Saint Lucie, Florida, 34987
Valley Hospital
Ridgewood, New Jersey, 07450
University of Rochester Medical Center
Rochester, New York, 14642
About this study
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
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).
Read the detailed 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.
- Conditions
- Cerebral Cavernous Malformation
- Being tested
- REC-994, Placebo
- Keywords
- Cerebral Cavernous Malformation, CCM
- Medical subject headings
- Hemangioma, Cavernous, Central Nervous System
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REC-994Drug
REC-994 200 mg tablets
PlaceboDrug
Placebo Tablets
| Study group | Role | What they receive |
|---|---|---|
| REC-994 200 mg | Experimental | Participants received REC-994 200 milligrams (mg) orally once daily (QD)
(1 200 mg REC-994 tablet, 1 matching placebo tablet) Receives: Drug: REC-994; Drug: Placebo |
| REC-994 400 mg | Experimental | Participants received REC-994 400 mg orally QD (2 200 mg REC-994 tablets) Receives: Drug: REC-994 |
| Placebo | Placebo comparator | Participants received matching placebo orally QD (2 matching placebo tablets) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. TEAES which include treatment related TEAEs, serious TEAEs, treatment-related serious TEAEs, TEAEs leading to treatment discontinuation, and treatment-related TEAEs leading to treatment discontinuation are reported. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section
Measured: Up to a maximum of 1201 days
Secondary outcomes (8)
Part 1: Change From Baseline in Modified Rankin Scale (mRS) Score at Month 12
The mRS is used for measuring the degree of disability or dependence in the daily activities of people who have suffered an acute stroke. The mRS score was calculated from a 6-point scale runs from 0-5, corresponding to no symptoms at all (0) to severe (5). A negative change from baseline indicated an improvement in symptoms. Change from baseline at Month 12 was analyzed by mixed model repeated measures (MMRM) method. The model included the change from baseline at visit as the dependent variable, with baseline score as covariate, treatment, visit, and treatment by visit interaction as fixed effects. Participant was included as a random effect using an unstructured covariance structure.
Measured: Baseline, Month 12
Part 1: Change From Baseline in Total SymptoMScreen (SMSS) Score at Month 12
The SMSS questionnaire is a self-assessment tool consists of 12 critical neurologic items, each assessed on a seven-point Likert scale ranging from 0 (not at all affected) to 6 (total limitation). The total score ranged from 0 to 72, with higher scores indicating more severe symptoms. A negative change from baseline indicated an improvement in symptoms. Change from baseline at Month 12 was analyzed by MMRM method. The model included the change from baseline at visit as the dependent variable, with baseline score as covariate, treatment, visit, and treatment by visit interaction as fixed effects. Participant was included as a random effect using an unstructured covariance structure.
Measured: Baseline, Month 12
Part 1: Change From Baseline in Cerebral Cavernous Malformation Health Index (CCM-HI) Total Score at Month 12
The CCM-HI is a novel patient-reported outcome to assess overall symptom burden across 20 domains. The total CCM-HI score was calculated as a weighted sum of subscale scores, with higher scores indicating greater disease burden. Subscale scores were derived by multiplying individual item responses (scored 0-4) by predefined weights and summing within each subscale. Each subscale score is then multiplied by a corresponding scaling factor. The weighted subscale scores were summed to generate a total score ranging from 0 to 100, with higher scores reflecting more severe symptoms. A negative change from baseline indicated an improvement in symptoms. Change from baseline at Month 12 were analyzed by MMRM method. The model included the change from baseline at visit as the dependent variable, with baseline score as covariate, treatment, visit, and treatment by visit interaction as fixed effects. Participant was included as a random effect using an unstructured covariance structure.
Measured: Baseline, Month 12
Part 1: Clinical Global Impressions - Improvement (CGI-I) Scale Score at Month 12
The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. The model included the CGI-I score at each visit as the dependent variable, with corresponding baseline score as covariate, treatment, visit, and treatment by visit interaction as fixed effects. Participant was included as a random effect using an unstructured covariance structure.
Measured: Month 12
Part 1: Patient Global Impressions - Improvement (PGI-I) Scale Score at Month 12
The PGI is a 7-point scale that requires the participant to assess how much their own illness has improved or worsened relative to a baseline state at the beginning of the intervention and was rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. The model included the PGI-I score at each visit as the dependent variable, with corresponding baseline score as covariate, treatment, visit, and treatment by visit interaction as fixed effects. Participant was included as a random effect using an unstructured covariance structure.
Measured: Month 12
Part 1: Change From Baseline in Number of Monthly Seizures at Month 12
Number of monthly seizures was calculated during each analysis window as follows: (number of observed seizures in each interval/number of days with seizure diary entry during each interval) x 30. Change from Baseline over monthly intervals was reported with a negative change indicating a reduction in the number of seizures.
Measured: Baseline, Month 12
Part 1: Change From Baseline in Number of Monthly Headaches at Month 12
Number of monthly headaches was calculated during each analysis window as follows: (number of observed headaches in each interval/number of days with headache diary entry during each interval) x 30. Change from Baseline over monthly intervals was reported with a negative change indicating a reduction in the number of seizures.
Measured: Baseline, Month 12
Number of Participants With Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) Confirmed Cerebral Haemorrhagic Events
MRI and/or CT scan were used to confirm evidence of symptomatic cerebral hemorrhagic events.
Measured: Up to a maximum 1201 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2021
- Study start17 Mar 2022
- Primary completion30 Jun 2025
- Study completion30 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cerebral Cavernous MalformationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Recursion Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05085561
- Sponsor's protocol ID
- REC-994-201
- Acronym
- SYCAMORE
- Status last verified
- Sep 2026
- First submitted
- 8 Oct 2021
- Last updated
- 22 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05085561
- Acronym / sponsor ID
- SYCAMORE / REC-994-201
- Conditions
- Cerebral Cavernous Malformation
- Keywords
- Cerebral Cavernous Malformation, CCM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Recursion Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Mar 2022 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 30 Jun 2025 (actual)
- First posted
- 20 Oct 2021 (actual)
- Results
- Posted 22 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| REC-994 200 mg | Experimental | Drug: REC-994, Drug: PlaceboParticipants received REC-994 200 milligrams (mg) orally once daily (QD) (1 200 mg REC-994 tablet, 1 matching placebo tablet) |
| REC-994 400 mg | Experimental | Drug: REC-994Participants received REC-994 400 mg orally QD (2 200 mg REC-994 tablets) |
| Placebo | Placebo comparator | Drug: PlaceboParticipants received matching placebo orally QD (2 matching placebo tablets) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years of age or older with anatomic CCM lesions demonstrated by brain MRI
- Have symptomatic CCM
- Have provided written informed consent to participate in the study
- 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
Key exclusion criteria (10 listed)
- Symptoms deemed by the study Investigator to be caused exclusively by irreversible neuronal damage from prior stroke or neurosurgical instrumentation
- History of cranial irradiation or surgical/radiosurgical treatment of the primary symptomatic CCM lesion
- Pregnant or breast feeding
- Be unable or unwilling to participate in MRI assessments (e.g., claustrophobia, metal implant or implanted cardiac pacemaker)
- Liver dysfunction or active liver disease as defined by baseline serum transaminases >2x upper limit of normal (ULN)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| REC-994REC-994 200 mg tablets | Drug | REC-994 200 mg, REC-994 400 mg |
| PlaceboPlacebo Tablets | Drug | Placebo, REC-994 200 mg |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to a maximum of 1201 days
A TEAE was the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. TEAES which include treatment related TEAEs, serious TEAEs, treatment-related serious TEAEs, TEAEs leading to treatment discontinuation, and treatment-related TEAEs leading to treatment discontinuation are reported. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section
8 secondary outcomes
Part 1: Change From Baseline in Modified Rankin Scale (mRS) Score at Month 12
Time frame: Baseline, Month 12
Part 1: Change From Baseline in Total SymptoMScreen (SMSS) Score at Month 12
Time frame: Baseline, Month 12
Part 1: Change From Baseline in Cerebral Cavernous Malformation Health Index (CCM-HI) Total Score at Month 12
Time frame: Baseline, Month 12
Part 1: Clinical Global Impressions - Improvement (CGI-I) Scale Score at Month 12
Time frame: Month 12
Part 1: Patient Global Impressions - Improvement (PGI-I) Scale Score at Month 12
Time frame: Month 12
Part 1: Change From Baseline in Number of Monthly Seizures at Month 12
Time frame: Baseline, Month 12
Part 1: Change From Baseline in Number of Monthly Headaches at Month 12
Time frame: Baseline, Month 12
Number of Participants With Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) Confirmed Cerebral Haemorrhagic Events
Time frame: Up to a maximum 1201 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing REC-994 in people with Cerebral Cavernous Malformation, run by Recursion Pharmaceuticals Inc. at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: Up to a maximum of 1201 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.