Evaluate REC-4881 in Patients With FAP

Familial Adenomatous Polyposis Clinical Trial

— TUPELO  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05552755
• Other study ID #: REC-4881-201
• Status: Recruiting
• Phase: Phase 1/Phase 2
• 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
• 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

Related Conditions & MeSH terms

• Adenomatous Polyposis Coli
• Familial Adenomatous Polyposis

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)