RECRUITING

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

Conditions

Familial Adenomatous Polyposis FAP APC mutation adenomatous polyposis coli desmoid disease

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Phase 1b-2, Multicenter, Trial to Evaluate the Efficacy, Safety, Pharmacokintetics, and Pharmacodynamics of REC-4881 in Patients With Familial Adenomatous Polyposis (FAP)

Quick Facts

Study Start:2023-07-10

Study Completion:2026-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05552755

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Male or female and ≥ 18 years of age 2. Have provided written informed consent to participate in the study 3. Diagnosis of phenotypic classical FAP with disease involvement of the duodenum or the residual colon/rectum/pouch as the primary disease site. 4. Genetic diagnosis of FAP with APC gene mutation (Part 2 only). 5. Has undergone colectomy or subtotal colectomy 6. Spigelman Classification Stage II or higher. 7. Investigator/Participant agrees to leave polyps ≤10 mm unresected during endoscopies performed at Screening and while on study 8. Have no significant cardiovascular abnormalities at Screening: 1. Left ventricular ejection fraction \>50% as determined on screening echocardiogram (ECHO)/ multi-gated acquisition (MUGA) 2. A QT interval corrected for heart rate using the Fridericia formula (QTcF) \< 450 msec in men and \<470 milliseconds (msec) in women. 9. Have no significant hematopoietic abnormalities at Screening: 1. White blood cell count (WBC) ≥ 3,000/cubic millimeters (mm\^3) (non-black populations); 2,700/mm\^3 (black populations) 2. Platelet count ≥ 120,000/mm\^3 3. Hemoglobin ≥ 10.0 grams (g)/deciiter (dL) 4. No history of clinical coagulopathy. 10. Have no significant hepatic abnormalities at Screening: 1. Total bilirubin ≤ 1.5 \* upper limit of normal (ULN) (individuals with Gilbert syndrome may be enrolled) 2. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) ≤ 2.0 \* ULN. 11. Have no significant renal abnormalities at Screening: serum creatinine ≤ 1.5 times \* ULN. 12. Female participants who are women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours before the first dose of study drug. If the urine test is positive or cannot be confirmed negative, a serum pregnancy test will be required and must be negative for the participant to be eligible. 13. All participants must be willing to follow the contraceptive guidance in the protocol and must not be lactating or planning to attempt to become pregnant during the study or for a further period of 4 months after the last dose of study drug or impregnate someone during this study or for a further period of 14 weeks after the last dose of study drug. 14. Absence of gross blood in stool at Screening; red blood on toilet paper only is acceptable. 15. Participant must be willing to discontinue use of non-steroidal anti-inflammatory agents (NSAIDs) 6 weeks prior to Study Day 1 and remain off NSAIDs throughout the treatment period of the study (use of aspirin ≤ 700 milligrams \[mg\] week is allowed.)	1. 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. 2. Has had prior pelvic irradiation. 3. Has gastrointestinal disease or recent gastrointestinal procedure that could interfere with oral absorption of REC-4881, including difficulty swallowing capsules. 4. 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. 5. 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. 6. Is currently under treatment for desmoid tumors. 7. Use of omega-3 fatty acids or oral corticosteroids prior to Study Day 1 8. Use of strong cytochrome P3A (CYP3A) inhibitors or inducers prior to Study Day 1 9. History of an ongoing or newly diagnosed eye abnormality, including: 1. Retinal pathologies such as diabetic retinopathy, veno-occlusion, or macular edema 2. Corneal pathologies such as herpes keratitis, corneal dystrophy, corneal erosions, corneal degeneration, active or recurrent keratitis, or uveitis (intermittent, posterior, and/or panuveitis) 3. Other clinically significant ophthalmologic abnormalities (for example, retinal detachment) or has findings at Screening. \[Participants with corrected myopia may be enrolled.\] 10. Has cancer at screening endoscopy in gastrointestinal (GI) tract (including stomach, duodenum, and colon/rectum/pouch) (Part 2 only). 11. Has a large polyp (\>1 centimeter \[cm\]) not amenable to complete removal 12. Has active pancreatitis secondary to pancreatic duct obstruction 13. Has active gall bladder disease 14. Is pregnant, lactating or is planning to attempt to become pregnant during this study or within 4 months after the last dose of study drug (women) or is planning to attempt to impregnate someone or donate sperm during the study or within 14 weeks after the last dose of study drug (men). 15. Has had major surgery prior to Study Day 1 16. Has an active infection requiring systemic therapy. 17. Has known hypersensitivity to the study drug or its excipients. 18. Has a history of alcohol or substance abuse within 1 year prior to screening for study participation, or is currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner which, in the opinion of the Investigator, indicates abuse. 19. Received treatment with another mitogen-activated protein kinase (MEK) inhibitor 8 weeks prior to Screening and throughout the treatment period of the study. 20. Any of the following known active infections: 1. Human immunodeficiency virus (HIV) not optimally controlled or treated. Participants with HIV who are on sustained stable antiretrovirals (for \>4 weeks) and have cluster of differentiation (CD)4+ counts ≥ 350 cells/microliter (μL) may be enrolled. No HIV testing is required unless clinically indicated or mandated by local health authority. 2. Chronic hepatitis B virus (HBV) infection with surface antigen positive: participants with a prior history of treated HBV infection who are hepatitis B surface antigen-negative may be enrolled. No testing is required for hepatitis B unless clinically indicated or mandated by local health authority. 3. Chronic hepatitis C virus (HCV) infection: untreated or on active treatment. Participants with a prior history of treated HCV infection who are HCV RNA-undetectable may be enrolled. No testing is required for hepatitis C unless clinically indicated or mandated by local health authority. 21. Has a severe or uncontrolled medical condition (for example, dermatologic disease, etc.) that, in the opinion of the Investigator, would pose a significant clinical risk for the participant. 22. Use of strong Breast Cancer Resistance Protein (BCRP) or Multidrug Resistance-Associated Protein 2 (MRP2) inhibitors within 14 days of Study Day 1 and throughout the treatment period of the study. 23. Clinically significant cardiovascular disease ≤ 6 months before first dose 1. Myocardial infarction or unstable angina 2. Clinically significant cardiac arrhythmias 3. Uncontrolled hypertension: systolic blood pressure (SBP) \> 180 millimeters of mercury (mmHg), diastolic blood pressure (DBP) \> 100 mmHg 4. Pulmonary embolism, symptomatic cerebrovascular events or any other serious cardiac condition (for example, pericardial effusion or restrictive cardiomyopathy) 5. QTcF prolongation \>450 msec in males and \>470 msec in females at screening or history of long QTc syndrome 6. Congestive heart failure (New York Heart Association class III-IV) 7. Myocarditis / clinically significant pericarditis. 8. Atrial enlargement.

Inclusion Criteria

Exclusion Criteria

1. Male or female and ≥ 18 years of age
2. Have provided written informed consent to participate in the study
3. Diagnosis of phenotypic classical FAP with disease involvement of the duodenum or the residual colon/rectum/pouch as the primary disease site.
4. Genetic diagnosis of FAP with APC gene mutation (Part 2 only).
5. Has undergone colectomy or subtotal colectomy
6. Spigelman Classification Stage II or higher.
7. Investigator/Participant agrees to leave polyps ≤10 mm unresected during endoscopies performed at Screening and while on study
8. Have no significant cardiovascular abnormalities at Screening:
1. Left ventricular ejection fraction \>50% as determined on screening echocardiogram (ECHO)/ multi-gated acquisition (MUGA)
2. A QT interval corrected for heart rate using the Fridericia formula (QTcF) \< 450 msec in men and \<470 milliseconds (msec) in women.
9. Have no significant hematopoietic abnormalities at Screening:
1. White blood cell count (WBC) ≥ 3,000/cubic millimeters (mm\^3) (non-black populations); 2,700/mm\^3 (black populations)
2. Platelet count ≥ 120,000/mm\^3
3. Hemoglobin ≥ 10.0 grams (g)/deciiter (dL)
4. No history of clinical coagulopathy.
10. Have no significant hepatic abnormalities at Screening:
1. Total bilirubin ≤ 1.5 \* upper limit of normal (ULN) (individuals with Gilbert syndrome may be enrolled)
2. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) ≤ 2.0 \* ULN.
11. Have no significant renal abnormalities at Screening: serum creatinine ≤ 1.5 times \* ULN.
12. Female participants who are women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours before the first dose of study drug. If the urine test is positive or cannot be confirmed negative, a serum pregnancy test will be required and must be negative for the participant to be eligible.
13. All participants must be willing to follow the contraceptive guidance in the protocol and must not be lactating or planning to attempt to become pregnant during the study or for a further period of 4 months after the last dose of study drug or impregnate someone during this study or for a further period of 14 weeks after the last dose of study drug.
14. Absence of gross blood in stool at Screening; red blood on toilet paper only is acceptable.
15. Participant must be willing to discontinue use of non-steroidal anti-inflammatory agents (NSAIDs) 6 weeks prior to Study Day 1 and remain off NSAIDs throughout the treatment period of the study (use of aspirin ≤ 700 milligrams \[mg\] week is allowed.)

1. 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.
2. Has had prior pelvic irradiation.
3. Has gastrointestinal disease or recent gastrointestinal procedure that could interfere with oral absorption of REC-4881, including difficulty swallowing capsules.
4. 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.
5. 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.
6. Is currently under treatment for desmoid tumors.
7. Use of omega-3 fatty acids or oral corticosteroids prior to Study Day 1
8. Use of strong cytochrome P3A (CYP3A) inhibitors or inducers prior to Study Day 1
9. History of an ongoing or newly diagnosed eye abnormality, including:
1. Retinal pathologies such as diabetic retinopathy, veno-occlusion, or macular edema
2. Corneal pathologies such as herpes keratitis, corneal dystrophy, corneal erosions, corneal degeneration, active or recurrent keratitis, or uveitis (intermittent, posterior, and/or panuveitis)
3. Other clinically significant ophthalmologic abnormalities (for example, retinal detachment) or has findings at Screening. \[Participants with corrected myopia may be enrolled.\]
10. Has cancer at screening endoscopy in gastrointestinal (GI) tract (including stomach, duodenum, and colon/rectum/pouch) (Part 2 only).
11. Has a large polyp (\>1 centimeter \[cm\]) not amenable to complete removal
12. Has active pancreatitis secondary to pancreatic duct obstruction
13. Has active gall bladder disease
14. Is pregnant, lactating or is planning to attempt to become pregnant during this study or within 4 months after the last dose of study drug (women) or is planning to attempt to impregnate someone or donate sperm during the study or within 14 weeks after the last dose of study drug (men).
15. Has had major surgery prior to Study Day 1
16. Has an active infection requiring systemic therapy.
17. Has known hypersensitivity to the study drug or its excipients.
18. Has a history of alcohol or substance abuse within 1 year prior to screening for study participation, or is currently using alcohol, drugs of abuse, or any prescribed or over-the-counter medication in a manner which, in the opinion of the Investigator, indicates abuse.
19. Received treatment with another mitogen-activated protein kinase (MEK) inhibitor 8 weeks prior to Screening and throughout the treatment period of the study.
20. Any of the following known active infections:
1. Human immunodeficiency virus (HIV) not optimally controlled or treated. Participants with HIV who are on sustained stable antiretrovirals (for \>4 weeks) and have cluster of differentiation (CD)4+ counts ≥ 350 cells/microliter (μL) may be enrolled. No HIV testing is required unless clinically indicated or mandated by local health authority.
2. Chronic hepatitis B virus (HBV) infection with surface antigen positive: participants with a prior history of treated HBV infection who are hepatitis B surface antigen-negative may be enrolled. No testing is required for hepatitis B unless clinically indicated or mandated by local health authority.
3. Chronic hepatitis C virus (HCV) infection: untreated or on active treatment. Participants with a prior history of treated HCV infection who are HCV RNA-undetectable may be enrolled. No testing is required for hepatitis C unless clinically indicated or mandated by local health authority.
21. Has a severe or uncontrolled medical condition (for example, dermatologic disease, etc.) that, in the opinion of the Investigator, would pose a significant clinical risk for the participant.
22. Use of strong Breast Cancer Resistance Protein (BCRP) or Multidrug Resistance-Associated Protein 2 (MRP2) inhibitors within 14 days of Study Day 1 and throughout the treatment period of the study.
23. Clinically significant cardiovascular disease ≤ 6 months before first dose
1. Myocardial infarction or unstable angina
2. Clinically significant cardiac arrhythmias
3. Uncontrolled hypertension: systolic blood pressure (SBP) \> 180 millimeters of mercury (mmHg), diastolic blood pressure (DBP) \> 100 mmHg
4. Pulmonary embolism, symptomatic cerebrovascular events or any other serious cardiac condition (for example, pericardial effusion or restrictive cardiomyopathy)
5. QTcF prolongation \>450 msec in males and \>470 msec in females at screening or history of long QTc syndrome
6. Congestive heart failure (New York Heart Association class III-IV)
7. Myocarditis / clinically significant pericarditis.
8. Atrial enlargement.

Contacts and Locations

Study Contact

Recursion Pharmaceuticals

CONTACT

385-374-1724

clinicaltrials@recursionpharma.com

Study Locations (Sites)

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85259

United States

Del Sol Research Management

Tucson, Arizona, 85715

United States

Medical Associates Research Group

San Diego, California, 92123

United States

GI Pros

Naples, Florida, 34102

United States

Digestive and Liver Center of Florida

Orlando, Florida, 32825

United States

Gastroenterology Health Partners, PLLC

New Albany, Indiana, 47150

United States

Tandem Clinical Research

Marrero, Louisiana, 70072

United States

Corewell Health (Spectrum Health Hospitals Colorectal Cancer Multis)

Grand Rapids, Michigan, 49503

United States

Mayo Clinic - Rochester

Rochester, Minnesota, 55905

United States

Washington University School of Medicine

St Louis, Missouri, 63110

United States

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Gastro One-8110 Walnut Rs

Cordova, Tennessee, 38108

United States

Vanderbilt Digestive Center

Nashville, Tennessee, 37232

United States

Genetic Cancer Prevention Clinic - UT Southwestern

Dallas, Texas, 75390

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Huntsman Cancer Institute and University of Utah

Salt Lake City, Utah, 84112

United States

Benaroya Research Institute at Virginia Mason

Seattle, Washington, 98101

United States

Collaborators and Investigators

Sponsor: Recursion Pharmaceuticals Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-10

Study Completion Date2026-07

Study Record Updates

Study Start Date2023-07-10

Study Completion Date2026-07

Terms related to this study

Keywords Provided by Researchers

FAP
familial adenomatous polyposis
APC mutation
adenomatous polyposis coli
desmoid disease

Additional Relevant MeSH Terms

Familial Adenomatous Polyposis