Safety and Efficacy of PBF-677 in Ulcerative Colitis Patients

NCT03773952 | Completed Phase 2

• 1 other identifier: PBF-677-3
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase IIa (proof of concept), randomized, double blind, placebo-controlled, multicentre clinical trial to evaluate the safety and efficacy of daily PBF-677 oral treatment during 28 days in Ulcerative colitis (UC) patients who are not receiving immunosuppressants and present mild-to-moderate activity of the disease. Enrolled patients would receive standard high doses of 5-ASA (4g), according to current clinical guidelines, and are randomized to receive also PBF-677 or placebo.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Number of subjects with treatment-related adverse events as assessed by CTCAE v4.03"

  Adverse events will be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. If

  28 Days

Secondary Outcomes (6)

• Effect of PBF-677 on Faecal calprotectin levels

  28 Days

• Effect of PBF-677 on Ulcerative Colitis activity

  28 Days

• Pharmacokinetic PBF-677 peak concentration in plasma

  Day 1 and Day 14

• Pharmacokinetic Time to PBF-677 peak concentration in plasma "Tmax"

  Day 1 and Day 14

• Pharmacokinetic Area under curve (AUC) of PBF-677 in plasma

  Day 1 and Day 14

Study Arms (2)

Oral 5-ASA + PBF-677 200 mg

EXPERIMENTAL

Oral Mesalazine (5-ASA) (4g) + PBF-677 (200mg)

Drug: PBF-677

Oral 5-ASA + Placebo oral Capsules

PLACEBO COMPARATOR

Oral Mesalazine (5-ASA) (4g) + Placebo oral capsules

Drug: Placebo oral capsule

Interventions

PBF-677 DRUG

oral small molecule, antagonist of Adenosine A3 receptor (AA3R)

Oral 5-ASA + PBF-677 200 mg

Placebo oral capsule DRUG

Oral capsules

Oral 5-ASA + Placebo oral Capsules

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to provide written informed consent
• Male or Female, 18 to 75 years of age, inclusive
• Patient with previous diagnosis of ulcerative colitis: ulcerative proctitis, left-side ulcerative colitis or extensive/pancolitis (E1, E2 and E3 of Montreal Classification, respectively) established at least 3 months prior to screening and determined by ordinary clinical, endoscopic, and histological procedures.
• Patient who has stable oral 5-ASA dose \< 4 gr/day treatment, within 1 month prior to screening.
• Mild-to-moderate activity of the disease determined clinically during the screening period by Partial Mayo Clinical Score of ≤ 6, with rectal bleeding score ≤ 2 and/or a bowel frequency score ≤ 2.
• Patient in flare of the disease.
• Patient with faecal calprotectin levels \> 50 mg/Kg
• Availability for the entire study period, absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; willingness to adhere to the protocol requirements, ability to cooperate adequately, to understand and follow the instructions of the physician or designee.
• Women who are not postmenopausal (at least 12 months) or surgically sterile must have a negative pregnancy test at screening and at the end of study and either abstain from sexual intercourse or use a highly effective method of birth control for the duration of the study and after 12 weeks after the last dose of study drug.
• For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm for the duration of the study and after 12 weeks from the last dose of study drug.

You may not qualify if:

• Patient who has treatment, within 3 months prior to screening, with immunomodulators including corticosteroids, azathioprine, mercaptopurine, biologics, tacrolimus, cyclosporine, for disease control.
• Patient who has stable oral 5-ASA dose ≥ 4 gr/day treatment, within 1 month prior to screening.
• Patient with C-reactive Protein levels (CRP) ≥ 10 mg/L
• Patient who has anti-diarrheal treatment, within 3 months prior to screening.
• Use of prescription medications started or with a dose adjustment within 4 weeks prior to study enrolment, or OTC medications or supplements started or with a dose adjustment within 2 weeks prior study enrolment.
• Use of products, food supplements or medical devices, whose composition includes probiotics in the 3 months prior to the selection.
• Patient who has fulminant or severe colitis, toxic megacolon, primary sclerosing cholangitis, Crohn's disease, history of colitis associated colonic dysplasia or active peptic ulcer disease.
• Patient who has prior extensive colonic resection, subtotal or total colectomy or planned surgery for UC
• Patient who has past or present fistula or abdominal abscess
• Patient who has clinically significant diseases and/or infections captured in the medical history or evidence of clinically significant findings on physical examination and/or clinically significant ordinary laboratory evaluations (haematology, biochemistry, and urinalysis) or ECG.
• Patient who has evidence of significant liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
• Patient who is currently participating in another clinical trial of an investigational drug or medical device within 90 days prior to screening.
• Patient who is pregnant or lactating
• Inability to comply with study protocol, in opinion of the investigator
• History of alcohol, drug or chemical abuse within 6 months prior to screening

Sponsors & Collaborators

• Palobiofarma SL: lead
• Qualitecfarma: collaborator

Study Sites (1)

Unidad de Enfermedad Inflamatoria Intestinal / IBD Unit. Servicio de Gastroenterología y Hepatología / Gastroenterology and Hepatology Dpt. Study Medical Coordinator Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized, double blind, placebo controlled, multicenter clinical trial

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 12, 2018
• Study Start: July 1, 2018
• Primary Completion: May 27, 2021
• Study Completion: May 27, 2021
• Last Updated: January 13, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)