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Familial Adenomatous PolyposisPhase 1/2TUPELONCT05552755

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

A Phase 1/2 study testing REC-4881 in people with Familial Adenomatous Polyposis, run by Recursion Pharmaceuticals Inc. at 17 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a multicenter, two-part trial in participants with FAP. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Familial Adenomatous Polyposis
What is being tested?
REC-4881
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
67 participants
Where
17 sitesUnited States
Study dates
10 Jul 2023to Sep 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • 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.
Show all 23Show fewer
  • 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.
  • Have no significant hepatic abnormalities at Screening:
  • Total bilirubin ≤ 1.5 * upper limit of normal (ULN) (individuals with Gilbert syndrome may be enrolled)
  • Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) ≤ 2.0 * ULN.
  • Have no significant renal abnormalities at Screening: serum creatinine ≤ 1.5 times * ULN.
  • 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.
  • 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.
  • Absence of gross blood in stool at Screening; red blood on toilet paper only is acceptable.
  • 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.)

Who cannot join

  • 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.
Show all 37Show fewer
  • 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
  • Has active gall bladder disease
  • 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).
  • Has had major surgery prior to Study Day 1
  • Has an active infection requiring systemic therapy.
  • Has known hypersensitivity to the study drug or its excipients.
  • 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.
  • Received treatment with another mitogen-activated protein kinase (MEK) inhibitor 8 weeks prior to Screening and throughout the treatment period of the study.
  • Any of the following known active infections:
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Clinically significant cardiovascular disease ≤ 6 months before first dose
  • Myocardial infarction or unstable angina
  • Clinically significant cardiac arrhythmias
  • Uncontrolled hypertension: systolic blood pressure (SBP) > 180 millimeters of mercury (mmHg), diastolic blood pressure (DBP) > 100 mmHg
  • Pulmonary embolism, symptomatic cerebrovascular events or any other serious cardiac condition (for example, pericardial effusion or restrictive cardiomyopathy)
  • QTcF prolongation >450 msec in males and >470 msec in females at screening or history of long QTc syndrome
  • Congestive heart failure (New York Heart Association class III-IV)
  • Myocarditis / clinically significant pericarditis.
  • Atrial enlargement.

Trial locations and contacts

17 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Recursion Pharmaceuticals contact

385-374-1724

clinicaltrials@recursion.com

17 sites in 1 country

United States17 sites, 7 recruiting

  • Gastro One-8110 Walnut Rs

    Cordova, Tennessee, 38108

    Terminated

  • Genetic Cancer Prevention Clinic - UT Southwestern

    Dallas, Texas, 75390

    Yamei Cheng, 214-645-4955, yamei.cheng@utsouthwestern.edu

    Luke Engelking, MD

    Recruiting

  • Corewell Health (Spectrum Health Hospitals Colorectal Cancer Multis)

    Grand Rapids, Michigan, 49503

    Active, not recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Diane Weber, (713) 563-5752, dweber@mdanderson.org

    Eduardo Vilar-Sanchez, MD

    Recruiting

  • Tandem Clinical Research

    Marrero, Louisiana, 70072

    Terminated

  • GI Pros

    Naples, Florida, 34102

    Withdrawn

  • Vanderbilt Digestive Center

    Nashville, Tennessee, 37232

    Casey Koza, (615) 875-6642, casey.koza@vumc.org

    Reid Ness, MD

    Recruiting

  • Gastroenterology Health Partners, PLLC

    New Albany, Indiana, 47150

    Withdrawn

  • Digestive and Liver Center of Florida

    Orlando, Florida, 32825

    Terminated

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Sophia Caterina, (215) 349-8222, sophia.caterina@pennmedicine.upenn.edu

    Bryson Katona, MD

    Recruiting

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55905

    Active, not recruiting

  • Huntsman Cancer Institute and University of Utah

    Salt Lake City, Utah, 84112

    Tavia Dutson, (801) 646-4172, Tavia.Dutson@hci.utah.edu

    Jessica Stout, MD

    Recruiting

  • Medical Associates Research Group

    San Diego, California, 92123

    Withdrawn

  • Mayo Clinic - Scottsdale

    Scottsdale, Arizona, 85259

    Active, not recruiting

  • Benaroya Research Institute at Virginia Mason

    Seattle, Washington, 98101

    Brooke Grubb, (206) 287-6260, brooke.grubb900@vmfh.org

    Emily Chesterfield, emily.chesterfield@vmfh.org

    Recruiting

  • Washington University School of Medicine

    St Louis, Missouri, 63110

    Asima Badic, 314-362-2646, asimabadic@wustl.edu

    Paul Wise, MD

    Recruiting

  • Del Sol Research Management

    Tucson, Arizona, 85715

    Withdrawn

Other trials in United States

About this study

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)

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

Read the detailed description

This is a Phase 1b/2 trial to evaluate efficacy, safety, pharmacokinetics and pharmacodynamics of REC-4881 in participants with FAP. This two-part study will treat participants with phenotypic classical FAP with disease involvement of the duodenum or the residual colon/rectum/pouch as the primary disease site.

Being tested
REC-4881, Placebo
Keywords
FAP, familial adenomatous polyposis, APC mutation, adenomatous polyposis coli, desmoid disease
Medical subject headings
Adenomatous Polyposis Coli

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • REC-4881Drug

    REC-4881 capsules

  • PlaceboDrug

    Placebo capsules

Study groups in NCT05552755
Study groupRoleWhat they receive
Placebo (Part 1)Placebo comparatorParticipants 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.
Receives: Drug: Placebo
REC-4881 4 mg (Part 1)ExperimentalParticipants will receive REC-4881 4 milligrams (mg) administered orally and then, following 14-28 days, participants will begin QD dosing for another 14 days.
Receives: Drug: REC-4881
REC-4881 4 mg (Part 2): QD Treatment RegimenExperimentalParticipants will receive REC-4881 4 mg administered orally QD for 12 weeks followed by a 12 week off-treatment period.
Receives: Drug: REC-4881
REC-4881 8 mg (Part 2): QD Treatment RegimenExperimentalParticipants will receive REC-4881 8 mg administered orally QD for 12 weeks followed by a 12 week off-treatment period.
Receives: Drug: REC-4881
REC-4881 4 mg (Part 2): Interval Dosing Treatment RegimenExperimentalParticipants will receive REC-4881 4 mg administered orally in a 7 day on and off schedule for 24 weeks.
Receives: Drug: REC-4881

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Day 1 through Day 43

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

    Measured: Day 1 through Day 43

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

    Measured: Day 1 through Day 43

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

    Measured: Day 1 through up to Week 37

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

    Measured: First 28 days of treatment

  6. Part 2: Number of Participants Who Discontinued Treatment

    Measured: Day 1 through up to Week 37

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

    Measured: Day 1 through up to Week 37

  8. Part 2: Percent Change From Baseline in Polyp Burden

    Measured: Baseline, up to Week 37

Secondary outcomes (11)

  1. Part 1: Number of Participants With TEAEs and SAEs

    Measured: Day 1 through Day 29

  2. Part 1: Number of Participants Who Discontinued Treatment

    Measured: Day 1 through Day 29

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

    Measured: Day 1 through Day 29

  4. Part 2: Cmax of REC-4881

    Measured: Week 1 and Week 3

  5. Part 2: Tmax of REC-4881

    Measured: Week 1 and Week 3

  6. Part 2: Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of REC-4881

    Measured: Week 1 and Week 3

  7. Part 2: Change From Baseline in Polyp Number

    Measured: Baseline, up to Week 37

  8. Part 2: Change From Baseline in Polyp Number >5 Millimeters (mm)

    Measured: Baseline, up to Week 37

  9. Part 2: Change From Baseline in Highest Histological Grade of Polyp

    Measured: Baseline, up to Week 37

  10. Part 2: Change From Baseline in Spigelman Stage Classification for Duodenal Polyps

    Measured: Baseline, up to Week 37

  11. Part 2: Change From Baseline in inSiGHT Stage for Rectal/Pouch Polyposis

    Measured: Baseline, up to Week 37

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2022
  2. Study start10 Jul 2023
  3. Primary completionJun 2027 (estimated)
  4. Study completionSep 2027 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
67 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05552755
Sponsor's protocol ID
REC-4881-201
Other IDs
2026-525282-50
Acronym
TUPELO
Status last verified
Jun 2026
First submitted
14 Sep 2022
Last updated
5 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing REC-4881 in people with Familial Adenomatous Polyposis, run by Recursion Pharmaceuticals Inc. at 17 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 23 inclusion and 37 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: looking for participants now, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Recursion Pharmaceuticals (385-374-1724, clinicaltrials@recursion.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Maximum (Peak) Plasma Drug Concentration (Cmax) of REC-4881 (time frame: Day 1 through Day 43). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05552755.

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 5 Jun 2026.

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