Evaluate REC-4881 in Patients with FAP
Purpose
This is a multicenter, two-part trial in participants with Familial Adenomatous Polyposis (FAP).
Condition
- Familial Adenomatous Polyposis
Eligibility
- Eligible Ages
- Over 55 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Male or female and ≥ 55 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. No significant cardiovascular abnormalities 7. Left ventricular ejection fraction of >50% as determined by echocardiogram 8. No significant hematopoietic abnormalities 9. No significant hepatic abnormalities 10. No significant renal abnormalities 11. Female participants must have a negative serum pregnancy test prior to Study Day 1 12. All participants must be willing to follow the contraceptive guidance in the protocol 13. Absence of gross blood in stool at Screening 14. Participant must be willing to discontinue use of non-steroidal anti-inflammatory agents (NSAIDs) prior to Study Day 1
Exclusion Criteria
- No clinically significant laboratory abnormality, medical or psychiatric illness 2. Has had prior pelvic irradiation. 3. Has gastrointestinal disease or recent gastrointestinal procedure that could interfere with oral absorption of REC-4881 4. Has received treatment with other investigational agents prior to Study Day 1 5. Treatment with other FAP-directed drug therapy within 8 weeks of screening endoscopy (Part 2 only). 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 CYP3A inhibitors or inducers prior to Study Day 1 9. History of an ongoing or newly diagnosed eye abnormality. 10. Cancer at screening endoscopy in GI tract (including stomach, duodenum, and colon/rectum/pouch) (Part 2 only). 11. Has a large polyp (>1 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 the study 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. History of alcohol or substance abuse. 19. Received treatment with another MEK inhibitor prior to Screening 20. Active or known HIV, hepatitis B or hepatitis C infections 21. Has a severe or uncontrolled medical condition 22. Use of strong BCRP or MRP2 inhibitors prior to Study Day 1 23. Has clinically significant cardiovascular disease within 6 months of Day 1 including myocardial infarction or unstable angina, cardiac arrhythmias, uncontrolled hypertension, pulmonary embolism, QTcF prolongation, Congestive heart failure, Myocarditis or clinically significant pericarditis
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Placebo Comparator Placebo (Part 1) |
Participants will receive placebo PO dosed once daily |
|
|
Experimental REC-4881 4mg (Part 1) |
Participants will receive REC-4881 4mg PO dosed once daily |
|
|
Experimental REC-4881 4mg (Part 2) |
Participants will receive REC-4881 4mg PO dosed once daily |
|
|
Experimental REC-4881 8mg (Part 2) |
Participants will receive REC-4881 8mg PO dosed once daily |
|
|
Experimental REC-4881 12mg (Part 2) |
Participants will receive REC-4881 12mg PO dosed once daily |
|
Recruiting Locations
Vanderbilt Digestive Center
Nashville, Tennessee 37232
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Recursion Pharmaceuticals Inc.
Detailed Description
This is a Phase 1b/2, trial to evaluate efficacy, safety, pharmacokinetics and pharmacodynamics of REC-4881 in participants with Familial Adenomatous Polyposis (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. Part 1 of the study enrolled seven participants with FAP who are post-colectomy/proctocolectomy. Participants were randomized to Placebo or REC-4881. Part 2 of the study will treat participants with escalating dose levels of REC-4881 during the Dose Finding. Participates in Cohort Expansion will be treated with a dose(s) to determine the RP2D.