REC-994 for Cerebral Cavernous Malformations

(SYCAMORE Trial)

No longer recruiting at 15 trial locations

Overseen By Recursion Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Recursion Pharmaceuticals Inc.

Disqualifiers: Pregnancy, Liver disease, Renal impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, REC-994, for individuals with symptomatic cerebral cavernous malformations (CCM), which are abnormal brain blood vessels that can cause headaches or seizures. Researchers aim to determine if REC-994 is safe and effective compared to a placebo (a pill with no active drug). The trial includes two groups receiving different doses of REC-994 to identify the most effective dose. Individuals with CCM confirmed by a brain MRI and who experience symptoms might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that REC-994 is likely to be safe for humans?

Research has shown that REC-994 is generally safe for humans. In one study, REC-994's safety profile matched that of a placebo, indicating that participants taking REC-994 experienced no more side effects than those taking a sugar pill. This finding applied to both the 200 mg and 400 mg doses. These results suggest that REC-994 is safe for people with cerebral cavernous malformations (CCM) in the short term. However, the trial ended due to a lack of long-term benefits, not because of safety concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cerebral cavernous malformations?

Unlike the standard care options for cerebral cavernous malformations, which mainly involve surgical interventions or symptom management, REC-994 offers a unique oral treatment approach. Researchers are excited about REC-994 because it targets the condition at a molecular level, potentially reducing the formation of cavernous malformations without invasive procedures. This treatment could provide a non-surgical option for patients, making management of the condition more accessible and less risky.

What evidence suggests that REC-994 might be an effective treatment for cerebral cavernous malformations?

Research has shown that REC-994 may help treat cerebral cavernous malformations (CCM). In this trial, participants will join different treatment arms, including a higher dose of REC-994 (400 mg), a lower dose (200 mg), and a placebo group. One study found that half of the patients taking the higher dose of REC-994 (400 mg) experienced improvements in their brain lesions. MRI scans showed that these lesions tended to be smaller at this dose compared to those in the placebo group. The treatment balances certain chemicals in the body, which can help manage the condition. While these results are promising, further research is needed to confirm its effectiveness. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with symptomatic cerebral cavernous malformation (CCM) confirmed by MRI. Participants must consent to the study and not have been in another drug trial within the past 28 days or 5 half-lives of any investigational drug. Exclusions include pregnancy, breastfeeding, inability to undergo MRI, liver or severe kidney issues, recent hemorrhage or brain surgery, history of muscle disorders or substance abuse.

Inclusion Criteria

I am over 18 and have CCM lesions in my brain shown by MRI.

Have provided written informed consent to participate in the study

I have symptoms from cerebral cavernous malformations.

Exclusion Criteria

My liver tests are more than twice the normal limit.

I cannot or do not want to undergo MRI scans due to claustrophobia or having a metal implant/pacemaker.

My symptoms are due to permanent nerve damage from a past stroke or brain surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive REC-994 or placebo in a double-blind manner to evaluate safety, efficacy, and pharmacokinetics

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-Term Blinded Extension

Participants continue to receive REC-994 or placebo to evaluate long-term safety, tolerability, and efficacy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• REC-994

Trial Overview The study tests REC-994 at two doses (200 mg and 400 mg) against a placebo in people with CCM. It's randomized and double-blind, meaning participants are put into groups by chance and neither they nor the researchers know who gets the real treatment versus placebo.

How Is the Trial Designed?

Group I: REC-994 200 mg Active Control 2 Interventions

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

Group II: REC-994 400 mg Active Control 1 Intervention

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

Group III: Placebo Placebo Group 1 Intervention

Matching Placebo po QD (2 matching placebo tablets)

Who Is Running the Clinical Trial?

Recursion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

450+

Citations

1. ir.recursion.com ir.recursion.com/news-releases/news-release-details/recursion-announces-phase-2-data-rec-994-first-disease

Recursion Announces Phase 2 Data of REC-994, a First-in ... REC-994 met its primary endpoint of safety and tolerability, demonstrating a similar profile across placebo and both 200mg and 400mg dosage-arms.

2. alliancetocure.org alliancetocure.org/home/research-clinical-trials/completed-research-projects/rec-994/

Recursion's REC-994 According to the results of the 62-person Phase II study, 50% of patients with cerebral lesions on the highest dose of REC-994 (400 mg) showed ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11040693/

Clinical pharmacology and tolerability of REC‐994, a redox ... REC‐994 restores ROS balance, and in double‐blind, placebo‐controlled, trials in healthy volunteers, had low potential for off‐target adverse ...

4. fiercebiotech.com fiercebiotech.com/biotech/recursions-phase-2-brain-disease-trial-yields-scant-evidence-efficacy

Recursion's brain disease trial shows scant evidence of ... Recursion said MRI scans showed “a trend towards reduced lesion volume and hemosiderin ring size” at the higher REC-994 dose compared to placebo ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05085561?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(Cerebral%20Cavernous%20Malformation)))&rank=4

The Symptomatic Cerebral Cavernous Malformation Trial ... 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 ...

6. synapse.patsnap.com synapse.patsnap.com/article/recursion-reports-phase-2-rec-994-data-meeting-safety-and-tolerability-endpoint-for-ccm

Recursion Reports Phase 2 REC-994 Data Meeting Safety ... The results revealed that REC-994 met its primary endpoint of safety and tolerability, showing comparable profiles across placebo and two dosage ...