TUPELO: Efficacy and Safety of REC-4881 in Participants With Familial Adenomatous Polyposis (FAP)

Sponsor

Recursion Pharmaceuticals Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05552755

Collaborator

(none)

171

Enrollment

Locations

Arms

37.9

Anticipated Duration (Months)

85.5

Patients Per Site

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 2, randomized, double-blind, placebo-controlled trial to evaluate efficacy, safety, and pharmacokinetics of REC-4881 in participants with Familial Adenomatous Polyposis (FAP).

Condition or Disease	Intervention/Treatment	Phase
Familial Adenomatous Polyposis	Drug: REC-4881 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

171 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blind, placebo-controlledRandomized, double-blind, placebo-controlled

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Efficacy, Safety, and Pharmacokinetics of REC-4881 in Patients With Familial Adenomatous Polyposis (FAP)

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2026

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: REC-4881 4mg Participants will receive REC-4881 4mg PO dosed QD	Drug: REC-4881 REC-4881 4mg capsules
Experimental: REC-4881 8mg Participants will receive REC-4881 8mg PO dosed QD	Drug: REC-4881 REC-4881 4mg capsules
Experimental: REC-4881 12mg Participants will receive REC-4881 12mg PO dosed QD	Drug: REC-4881 REC-4881 4mg capsules
Placebo Comparator: Placebo Participants will receive placebo PO dosed QD	Drug: Placebo Placebo capsules

Outcome Measures

Primary Outcome Measures

Maximum (peak) plasma drug concentration (Cmax) [Assessed pre-dose and at multiple timepoints up to 43 days (Part 1)]
Pharmacokinetics (PK) after single and multiple doses of REC-4881
Time to reach maximum (peak) plasma concentration (Tmax) [Assessed pre-dose and at multiple timepoints up to 43 days (Part 1)]
Pharmacokinetics (PK) after single and multiple doses of REC-4881
Area under the plasma concentration-time curve (AUC) [Assessed pre-dose and at multiple timepoints up to 43 days (Part 1)]
Pharmacokinetics (PK) after single and multiple doses of REC-4881
Mean change in polyp burden or ampullary lesion size [12 months (Part 2)]
Effect of REC-4881on rectal/pouch, duodenal, and ampullary adenoma progression assessed by endoscopy in patients with FAP

Secondary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [43 days (Part 1) and 12 months (Part 2)]
Adverse events (AEs) according to CTCAE v 5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥ 18 years of age
Diagnosis of phenotypic classical FAP with disease involvement of the duodenum and/or residual colon/rectum/pouch
Genetic diagnosis of FAP with APC gene mutation (Part 2 only)
Has undergone colectomy or subtotal colectomy; individual may not have an intact colon

Exclusion Criteria:

Prior pelvic irradiation
Gastrointestinal disease or recent gastrointestinal procedure that could interfere with oral absorption of REC-4881, including difficulty swallowing capsules
Received treatment with other investigational agents within the 4 weeks prior to initial dosing with study drug
Treatment with other FAP-directed drug therapy (including celecoxib, sulindac or fish oil) within 8 weeks of study screening
Regularly using aspirin in excess of 700 mg per week or NSAIDs at any dose.
Use of omega-3 fatty acids or oral corticosteroids within 30 days of initial dosing with study drug.
Currently taking any strong CYP3A inhibitors or inducers [Participants may discontinue use of these agents at least 14 days prior to screening and be eligible]
History of an ongoing or newly diagnosed eye abnormality
Cancer on biopsy at screening in GI tract (including stomach, duodenum, and colon/rectum/pouch)
Received treatment with another MEK inhibitor within 2 months of Screening.