Evaluate REC-4881 in Participants With Familial Adenomatous Polyposis (FAP)

NCT05552755 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: REC-4881-2012026-525282-50
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 17

Brief Summary

This is a multicenter, two-part trial in participants with FAP.

Conditions

Familial Adenomatous Polyposis

Keywords

FAP; familial adenomatous polyposis; APC mutation; adenomatous polyposis coli; desmoid disease

Outcome Measures

Primary Outcomes (8)

• Part 1: Maximum (Peak) Plasma Drug Concentration (Cmax) of REC-4881

  Day 1 through Day 43

• Part 1: Time to Reach Cmax (Tmax) of REC-4881

  Day 1 through Day 43

• Part 1: Area Under the Plasma Concentration-time Curve (AUC) of REC-4881

  Day 1 through Day 43

• Part 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Day 1 through up to Week 37

• Part 2: Number of Participants With Dose-limiting Toxicities (DLTs)

  First 28 days of treatment

• Part 2: Number of Participants Who Discontinued Treatment

  Day 1 through up to Week 37

• Part 2: Number of Participants With Dose Modification Due to Toxicity

  Day 1 through up to Week 37

• Part 2: Percent Change From Baseline in Polyp Burden

  Baseline, up to Week 37

Secondary Outcomes (11)

• Part 1: Number of Participants With TEAEs and SAEs

  Day 1 through Day 29

• Part 1: Number of Participants Who Discontinued Treatment

  Day 1 through Day 29

• Part 1: Number of Participants With Dose Modification Due to Toxicity

  Day 1 through Day 29

• Part 2: Cmax of REC-4881

  Week 1 and Week 3

• Part 2: Tmax of REC-4881

  Week 1 and Week 3

Study Arms (5)

Placebo (Part 1)

PLACEBO COMPARATOR

Participants will receive a single dose of placebo administered orally and then, following 14-28 days, participants will begin once daily (QD) dosing for another 14 days.

Drug: Placebo

REC-4881 4 mg (Part 1)

EXPERIMENTAL

Participants will receive REC-4881 4 milligrams (mg) administered orally and then, following 14-28 days, participants will begin QD dosing for another 14 days.

Drug: REC-4881

REC-4881 4 mg (Part 2): QD Treatment Regimen

EXPERIMENTAL

Participants will receive REC-4881 4 mg administered orally QD for 12 weeks followed by a 12 week off-treatment period.

Drug: REC-4881

REC-4881 8 mg (Part 2): QD Treatment Regimen

EXPERIMENTAL

Participants will receive REC-4881 8 mg administered orally QD for 12 weeks followed by a 12 week off-treatment period.

Drug: REC-4881

REC-4881 4 mg (Part 2): Interval Dosing Treatment Regimen

EXPERIMENTAL

Participants will receive REC-4881 4 mg administered orally in a 7 day on and off schedule for 24 weeks.

Drug: REC-4881

Interventions

REC-4881 DRUG

REC-4881 capsules

REC-4881 4 mg (Part 1); REC-4881 4 mg (Part 2): Interval Dosing Treatment Regimen; REC-4881 4 mg (Part 2): QD Treatment Regimen; REC-4881 8 mg (Part 2): QD Treatment Regimen

Placebo DRUG

Placebo capsules

Placebo (Part 1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female and ≥ 18 years of age
• Have provided written informed consent to participate in the study
• Diagnosis of phenotypic classical FAP with disease involvement of the duodenum or the residual colon/rectum/pouch as the primary disease site.
• Genetic diagnosis of FAP with APC gene mutation (Part 2 only).
• Has undergone colectomy or subtotal colectomy
• Spigelman Classification Stage II or higher.
• Investigator/Participant agrees to leave polyps ≤10 mm unresected during endoscopies performed at Screening and while on study
• Have no significant cardiovascular abnormalities at Screening:
• Left ventricular ejection fraction \>50% as determined on screening echocardiogram (ECHO)/ multi-gated acquisition (MUGA)
• A QT interval corrected for heart rate using the Fridericia formula (QTcF) \< 450 msec in men and \<470 milliseconds (msec) in women.
• Have no significant hematopoietic abnormalities at Screening:
• White blood cell count (WBC) ≥ 3,000/cubic millimeters (mm\^3) (non-black populations); 2,700/mm\^3 (black populations)
• Platelet count ≥ 120,000/mm\^3
• Hemoglobin ≥ 10.0 grams (g)/deciiter (dL)
• No history of clinical coagulopathy.

You may not qualify if:

• Has any clinically significant laboratory abnormality, medical or psychiatric illness which, in the opinion of the Investigator, could interfere with the conduct or interpretation of the study or put the participant at risk.
• Has had prior pelvic irradiation.
• Has gastrointestinal disease or recent gastrointestinal procedure that could interfere with oral absorption of REC-4881, including difficulty swallowing capsules.
• Has received treatment with other investigational agents within the 4 weeks prior to Study Day 1 or a period during which the investigational agent has not been cleared from the body (that is, at least a period of 5 half-lives, if known), whichever is longer.
• Treatment with other FAP-directed drug therapy (such as off-label use of Balsalazide) within 8 weeks of screening endoscopy (Part 2 only) or had a Whipple procedure.
• Is currently under treatment for desmoid tumors.
• Use of omega-3 fatty acids or oral corticosteroids prior to Study Day 1
• Use of strong cytochrome P3A (CYP3A) inhibitors or inducers prior to Study Day 1
• History of an ongoing or newly diagnosed eye abnormality, including:
• Retinal pathologies such as diabetic retinopathy, veno-occlusion, or macular edema
• Corneal pathologies such as herpes keratitis, corneal dystrophy, corneal erosions, corneal degeneration, active or recurrent keratitis, or uveitis (intermittent, posterior, and/or panuveitis)
• Other clinically significant ophthalmologic abnormalities (for example, retinal detachment) or has findings at Screening. \[Participants with corrected myopia may be enrolled.\]
• Has cancer at screening endoscopy in gastrointestinal (GI) tract (including stomach, duodenum, and colon/rectum/pouch) (Part 2 only).
• Has a large polyp (\>1 centimeter \[cm\]) not amenable to complete removal
• Has active pancreatitis secondary to pancreatic duct obstruction

Sponsors & Collaborators

• Recursion Pharmaceuticals Inc.: lead

Study Sites (17)

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259, United States

ACTIVE NOT RECRUITING

Del Sol Research Management

Tucson, Arizona, 85715, United States

WITHDRAWN

Medical Associates Research Group

San Diego, California, 92123, United States

WITHDRAWN

GI Pros

Naples, Florida, 34102, United States

WITHDRAWN

Digestive and Liver Center of Florida

Orlando, Florida, 32825, United States

TERMINATED

Gastroenterology Health Partners, PLLC

New Albany, Indiana, 47150, United States

WITHDRAWN

Tandem Clinical Research

Marrero, Louisiana, 70072, United States

TERMINATED

Corewell Health (Spectrum Health Hospitals Colorectal Cancer Multis)

Grand Rapids, Michigan, 49503, United States

RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Gastro One-8110 Walnut Rs

Cordova, Tennessee, 38108, United States

TERMINATED

Vanderbilt Digestive Center

Nashville, Tennessee, 37232, United States

RECRUITING

Genetic Cancer Prevention Clinic - UT Southwestern

Dallas, Texas, 75390, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Huntsman Cancer Institute and University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Benaroya Research Institute at Virginia Mason

Seattle, Washington, 98101, United States

RECRUITING

MeSH Terms

Conditions

Adenomatous Polyposis Coli

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Recursion Pharmaceuticals

CONTACT

385-374-1724; clinicaltrials@recursion.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 23, 2022
• Study Start: July 10, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)