Study to test whether PF-06480605 is safe and improves symptoms in patients with ulcerative colitis

• Register: EUCTR
• Last refreshed on: 10 December 2018
• Main ID: EUCTR2016-001158-16-PL
• Date of registration: 21/09/2016
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc. 235 East 42nd Street, New York, NY 10017
• Public title: Study to test whether PF-06480605 is safe and improves symptoms in patients with ulcerative colitis
• Scientific title: A PHASE 2A, MULTICENTER, SINGLE ARM, OPEN-LABEL, TWO-STAGE, STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06480605 IN SUBJECTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS
• Date of first enrolment: 23/09/2016
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001158-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Italy, Korea, Republic of, Netherlands, Poland, United States

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.

2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

3. Male and/or female subjects between =18 and =75 years of age at the time of informed consent.

4. Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use two highly effective methods of contraception throughout the study and until the Week 26 visit (or 98 days after the last dose of IP).
Women of childbearing potential (WOCBP) will be eligible for this study provided these women use two highly effective methods of contraception throughout the study and until the Week 26 visit (or 98 days after the last dose of IP), as outlined in Section 4.3.
Female subjects who are not of childbearing potential (ie, meet at least 1 of the following criteria):
•Have undergone a documented hysterectomy and/or bilateral oophorectomy;
•Have medically confirmed ovarian failure; or
•Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level confirming the post-menopausal state.
Note: For subjects in france, WOCBP are NOT eligible for this study.
5. A diagnosis of UC for =4 months. A biopsy report must be available to confirm the histological diagnosis in the subject’s source documentation. In addition, a report documenting disease duration and extent of disease (eg, proctosigmoiditis, left-sided colitis, and pancolitis) based upon prior endoscopy must also be available in source documentation.

6. Subjects with moderate to severe active UC as defined (via screening colonoscopy) by a total Mayo score of =6, with a rectal bleeding subscore of =1 and an endoscopic subscore of =2 on the Mayo.

7. Active disease beyond the rectum (>15 cm of active disease at the screening colonoscopy).

8. Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for UC:
•Steroids;
•Immunosuppressants (AZA [azathioprine], 6-MP, or MTX [methotrexate]);
•Anti-TNF inhibitors (eg, infliximab, adalimumab, or golimumab);
•Anti-integrin inhibitors (eg, vedolizumab).
For subjects in The Netherlands: Subjects must have inadequate response to, loss of response to, or intolerance to at least one biological therapy, such as an anti-TNF inhibitor.
9. Subjects currently receiving the following treatment for UC are eligible provided they have been on stable doses as described below:
•Oral 5-ASA or sulfasalazine stable dose for at least 4 weeks prior to baseline. If oral 5-ASA treatment has been recently discontinued, it must have been stopped for at least 2 weeks prior to total Mayo score screening procedures.
•Oral corticosteroids (prednisone equivalent up to 20 mg/day; budesonide up to 9 mg/day) stable dose for at least 2 weeks prior to baseline. If oral corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to total Mayo core screening procedures. Decreases in steroid use due to AEs are allowed.
•6-MP or AZA (=2.5 mg/kg) stable dose for 8 weeks prior to baseline. Decreases due to AEs are permitted.
Are the trial subjects under 18? no
Number of
Exclusion criteria:
1. Subjects with a diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or CD. Subjects with clinical findings suggestive of CD (eg, fistulae, granulomas on biopsy) are also excluded.

2. Subjects with an imminent need for surgery or with elective surgery scheduled to occur during the study.

3. Subjects with colonic dysplasia or neoplasia.

4. Subjects with toxic megacolon.

5. Subjects with primary sclerosing cholangitis.

6. Subjects with known colonic stricture.

7. Subjects with history of colonic or small bowel stoma.

8. Subjects with a history of colonic or small bowel obstruction or resection.

9. Abnormal findings on the chest x-ray film performed routinely before initiating a new biologic therapy, such as presence of tuberculosis (TB), general infections, heart failure, or malignancy. Chest x-ray examination may be performed up to 12 weeks prior to screening.

10. Any current evidence of untreated latent or active TB infection, evidence of prior or currently active TB by chest x-ray, residing with or frequent close contact with individual(s) with active TB. Subjects who have a positive Mantoux (PPD) tuberculin skin test or a positive Interferon Gamma Release Assay (IGRA to be tested at the site’s local lab where feasible) during screening or within 12 weeks prior to randomization.

11. Presence of active enteric infections (positive stool culture and sensitivity). The presence of Clostridium difficile or pseudomembranous colitis. Known active invasive fungal infections such as histoplasmosis or parasitic infections. Subjects with clinically significant underlying disease that could predispose the subjects to infections. A history of serious infection (requiring parenteral antibiotic and/or hospitalization) within 4 weeks before Day 1. Pyoderma gangrenosum is allowed.

12. Known history of human immunodeficiency virus (HIV) based on documented history with positive serological test, or positive HIV serologic test at screening, tested at the site’s local lab.

13. Presence of transplanted organ. Skin grafts to treat pyoderma gangrenosum are allowed.

14. Significant concurrent medical condition as judged by the investigator at the time of screening or baseline visit.

15. Prior evidence of liver injury or toxicity due to methotrexate.

16. Abnormality in hematology and/or chemistry profiles during screening as defined in the protocol.

17. Subjects receiving the following therapies within the designated time period or are expected to receive any of these therapies during the study period:
•>9 mg/day of oral budesonide or >20 mg/day of prednisone or equivalent oral systemic corticosteroid dose within 2 weeks prior to baseline.
•IV, IM (parenteral), or topical (rectal) treatment of 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to baseline.
•Biologics including anti-TNF inhibitors as described below:
- Infliximab within 8 weeks prior to baseline.
- Adalimumab within 8 weeks prior to baseline.
- Golimumab within 8 weeks prior to baseline.
•Anti-integrin inhibitors (eg, vedolizumab) within 12 weeks prior to baseline.
For subjects in France: Subjects must not have received any biologic treatment for at least 5 half-lives prior to first dose of PF-06480605. (eg, infliximab: 47.5 days, adalimumab: 70 days, golimumab: 70 days, vedolizumab: 125 days).
•Other investigational procedure(s) or

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Ulcerative colitis (UC)
MedDRA version: 20.1 Level: LLT Classification code 10045365 Term: Ulcerative colitis System Organ Class: 100000004856

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Product Code: PF-06480605
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: PF-06480605
Current Sponsor code: PF-06480605
Other descriptive name: PF-06480605
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 42.5-57.5

Primary Outcome(s)

Main Objective: - To evaluate the safety and tolerability of PF-06480605 in subjects with moderate to severe UC.
- To evaluate the efficacy of PF-06480605 in induction of endoscopic improvement (as assessed by Mayo endoscopic subscore) at Week 14 in subjects with moderate to severe UC.

Primary end point(s): - Safety and tolerability of PF-06480605: Treatment-Emergent Adverse Event (TEAEs), withdrawal due to AEs, and SAEs will be reported.
- Endoscopic improvement at Week 14 (defined as a Mayo endoscopic subscore of 0 or 1, and without friability).

Secondary Objective: - To evaluate the efficacy of PF-06480605 in induction of remission at Week 14 (defined as a total Mayo score = 2 with no individual subscore > 1) in subjects with moderate to severe UC.
- To evaluate the efficacy of PF-06480605 in induction of endoscopic remission at Week 14 (defined as a Mayo endoscopic subscore of 0) in subjects with moderate to severe UC.
- To describe the PK of PF-06480605 in subjects with moderate to severe UC.
- To evaluate the immunogenicity of PF-06480605 in subjects with moderate to severe UC.
- To evaluate disease and pathway related biomarkers (ie, hsCRP and fecal calprotectin), and serum total sTL1A.

Timepoint(s) of evaluation of this end point: - The safety laboratory tests will be performed at times defined in the Schedule of Activities, page 20 of the protocol.
- Endoscopic improvement will be assessed at Week 14

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - Endoscopic remission will be assessed at Week 14
- The laboratory tests will be performed at times defined in the Schedule of Activities, page 20 of the protocol.

Secondary end point(s): - Remission at Week 14 (defined as a total Mayo score = 2 with no individual subscore >1).
- Endoscopic remission at Week 14 (defined as a Mayo endoscopic subscore of 0).
- PF-06480605 plasma concentrations.
- Incidence of development of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs).
- Change from baseline in fecal calprotectin.
- Change from baseline in hsCRP.
- Change from baseline in serum total sTL1A.

Secondary ID(s)

B7541002

2016-001158-16-BE

Source(s) of Monetary Support

Pfizer Inc.