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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05552755
Other study ID # REC-4881-201
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date July 10, 2023
Est. completion date July 2026

Study information

Verified date March 2024
Source Recursion Pharmaceuticals Inc.
Contact Recursion Pharmaceuticals
Phone 385-374-1724
Email clinicaltrials@recursionpharma.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a multicenter, two-part trial in participants with Familial Adenomatous Polyposis (FAP).


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 73
Est. completion date July 2026
Est. primary completion date July 2026
Accepts healthy volunteers No
Gender All
Age group 55 Years and older
Eligibility Inclusion Criteria: 1. 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: 1. 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


Intervention

Drug:
REC-4881
REC-4881 4mg capsules
Placebo
Placebo capsules

Locations

Country Name City State
United States Tandem Clinical Research Marrero Louisiana
United States GI Pros Naples Florida
United States University of Pennsylvania Philadelphia Pennsylvania
United States Huntsman Cancer Institute and University of Utah Salt Lake City Utah
United States Medical Associates Research Group San Diego California
United States Benaroya Research Institute at Virginia Mason Seattle Washington
United States Del Sol Research Management Tucson Arizona

Sponsors (1)

Lead Sponsor Collaborator
Recursion Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Characterize plasma pharmacokinetic (PK) parameters of REC-4881 Maximum (peak) plasma drug concentration (Cmax), time to reach maximum (peak) plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC) Assessed at multiple timepoints from Day 1 through 43 days in Part 1
Primary Incidence of Treatment-Emergent Adverse Events Treatment Emergent Adverse Events, Serious Adverse Events, and treatment discontinuation and dose modification due to toxicity 16 weeks (Part 2)
Primary Evaluate totality of data to determine the Recommended Phase 2 Dose (RP2D) Determination of the RP2D 16 weeks (Part 2)
Primary Percent change from baseline in polyp burden Effect of REC-4881 on duodenal adenomas and rectal/pouch adenomas 12 weeks (Part 2)
Secondary Incidence of Treatment-Emergent Adverse Events Treatment Emergent Adverse Events, Serious Adverse Events, and treatment discontinuation and dose modification due to toxicity 43 days (Part 1)
Secondary Characterize plasma pharmacokinetic (PK) parameters of REC-4881 Maximum (peak) plasma drug concentration (Cmax), time to reach maximum (peak) plasma concentration (Tmax), and area under the plasma concentration-time curve (AUC) Assessed at multiple timepoints from Day 1 through Week 3 (Part 2)
Secondary Assess the effect of REC-4881 on polyp number, histological grade and disease score Change from baseline in polyp number, polyp number >5 mm, highest histological grade, spigelman stage classification for duodenal polyps, and inSiGHT stage for rectal/pouch polyps 12 weeks (Part 2)
Secondary Assess the pharmacodynamic (PD) effect of REC-4881, and correlation between PD and clinical outcome Percent inhibition of pERK at multiple timepoints Day 1 through Week 3 (Part 2)
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