A study to evaluate the efficacy and safety of PF 06480605 in adult participants with moderate to severe ulcerative colitis

• Register: EUCTR
• Last refreshed on: 2 May 2022
• Main ID: EUCTR2019-002698-74-BE
• Date of registration: 02/04/2020
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc
• Public title: A study to evaluate the efficacy and safety of PF 06480605 in adult participants with moderate to severe ulcerative colitis
• Scientific title: A PHASE 2B, MULTICENTER, RANDOMIZED, DOUBLEBLIND, PLACEBO CONTROLLED DOSE-RANGING STUDY TO EVALUATE THE EFFICACY, SAFETY, AND PHARMACOKINETICS OF PF-06480605 IN ADULT PARTICIPANTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS - Tuscany 2
• Date of first enrolment: 03/06/2020
• Target sample size: 240
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-002698-74
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 9
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Bulgaria, Canada, China, France, Germany, Hungary, India, Italy, Japan, Mexico, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Turkey, Ukraine, United Kingdom, 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. Male or female participants 18 to 75 years of age.
2. A diagnosis of UC for =3 months with endoscopy and pathology reports supporting the diagnosis, disease duration, and extent of disease.
3. Moderate to severe active UC as defined by a Total Mayo Score of =6, and an endoscopic subscore of =2.
4. Active disease beyond the rectum (>15 cm from the anal verge).
5. Failed or be intolerant of at least 1 of the following treatments.
Steroids, Immunosuppressants (azathioprine [AZA],
6-mercaptopurine [6-MP] or methotrexate [MTX]),
Anti-TNF inhibitors (eg, infliximab, adalimumab, or golimumab),
Anti-integrin inhibitors (eg, vedolizumab),
Anti-IL-12/23 inhibitors (eg, ustekinumab),
JAK inhibitors (eg, tofacitinib).
Participants currently receiving treatments for UC are eligible providing they have been and are anticipated to be on stable dose for the duration of the study.
6. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
7. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion criteria:
1. Diagnosis of ischemic colitis, infectious colitis, radiation colitis,
microscopic colitis, indeterminate colitis, or findings suggestive of Crohn’s disease (eg, skip lesions, fistulae/perianal disease, non-necrotizing granulomas, etc.).
2. Clinical signs of fulminant colitis or toxic megacolon.
3. Imminent need for surgery or with elective surgery scheduled to
occur during the study.
4. Evidence of colonic dysplasia, adenomas, or neoplasia
5. Participants who meet either of the 2 criteria below are considered at risk for colonic dysplasia, adenomas, or neoplasia and must have a colonoscopy prior to randomization:
a. If the participant has had extensive (ie greater than left sided) colitis for equal to or greater than 8 years or disease limited to left side of colon (ie distal to splenic flexure) for equal to or greater than 10 years, regardless of age, a colonoscopy within 1 year of screening visit is required to survey for dysplasia.
b. If the participant is equal to or greater than 50 years of age, a colonoscopy within 10 years of screening is required to exclude adenomatous polyps.
Participants with adenomatous polyps identified on screening endoscopy will be eligible after complete polypectomy and follow up surveillance per local guidelines is negative.
Or, If the participant is over 50 years of age, a colonoscopy within 10 years of screening is required to exclude adenomatous polyps. Participants with adenomatous polyps identified on screening endoscopy will be eligible after complete polypectomy and follow-up surveillance per local guidelines is negative.
6. Clinically significant infections within 6 months of baseline (eg those requiring hospitalization or parenteral antimicrobial therapy, or opportunistic infections)
7. Cancer or history of cancer or lymphoproliferative disease within 5 years of baseline (with the exception of adequately treated or excised non-metastatic basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ).
8. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results.
9. Use of prohibted prior/concomitant medications
10. Known exposure to anti-TL1A (PF 06480605) or any type of anti-TL1A therapy.
11. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product used in this study (whichever is longer). Note: local regulations or other factors may require more than 30 days.
12. A 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
13. Chest Radiograph or computed tomography scan showing abnormalities.
14. Infected with tuberculosis, (TB): Any evidence of untreated latent or active TB infection.
15. Presence of active enteric infections: Known pathogenic bacterial, parasitic, fungal infections, including Clostridium difficile.
16. Infected with human immunodeficiency virus, (HIV), Hepatitis B or C viruses.
17. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat, if deemed necessary:
• Hemoglobin ?8.0 g/dL or hematocr

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

Health Condition(s) or Problem(s) studied

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

A phase 2b randomised, double-blind, placebo controlled dose-ranging study in Adults with Moderate to Severe Ulcerative Colitis
MedDRA version: 20.0 Level: HLT Classification code 10009888 Term: Colitis (excl infective) System Organ Class: 100000004856

Intervention(s)

Product Name: PF-06480605
Product Code: PF-06480605
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PF-06480605
Current Sponsor code: PF-06480605
Other descriptive name: Anti-TL1A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: 1. To evaluate the efficacy of PF-06480605 in induction of clinical remission at Week 14 in participants with moderate to severe active UC.
2. To evaluate the safety and tolerability of PF-06480605 during the induction period (from baseline to Week 14) and during the chronic therapy period (from Week 14 to the End of Study Visit)

Primary end point(s): Proportion of participants achieving clinical remission (defined as a Total Mayo Score =2, with no individual subscore >1) at Week 14.
Incidence and severity of treatment emergent adverse events (TEAEs) during the induction period.
Incidence of serious adverse events (SAEs)
Incidence of AEs or SAEs leading to discontinuation
Incidence of clinically significant abnormalities in vital signs, ECGs and laboratory values.

Secondary Objective: 1. To evaluate the efficacy of PF-06480605 in inducing remission at Week 14 in participants with moderate to severe active UC.
2. To valuate the efficacy of PF-06480605 on endoscopic appearance at Week 14.
3. To characterize the PK of PF-06480605 during the induction period. To evaluate disease and pathway related biomarkers (ie, hsCRP and fecal calprotectin and serum sTL1A)
Tertiary Objectives
1. To evaluate the effect of PF-06480605 on clinical outcomes and quality of life.
2. To evaluate the effect of PF 06480605 compared to placebo on histopathology score.
3. To collect non banked samples (eg, intestinal biopsies, stool for microbiome and metabolomic analysis, serum for analysis of proteins and metabolomic profiling and blood for RNA analysis) for exploratory research.
4. To enable exploratory research through collection of banked biospecimens
5 .To conduct additional exploratory immunogenicity assessments.
6.To characterize the immunogenicity of PF-06480605

Timepoint(s) of evaluation of this end point: At weeks 14 and 56 unless otherwise specified above

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Individual timepoints as detailed above for each endpoint

Secondary end point(s): Proportion of participants achieving remission (FDA definition 1 - defined as endoscopic subscore = 0 or 1, stool frequency subscore = 0, and rectal bleeding subscore = 0) at Week 14.
Proportion of participants achieving remission (FDA definition 2 - defined as endoscopic subscore = 0 or 1, =1 point decrease from baseline to achieve a stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0) at Week 14.
Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 14.
Proportion of participants achieving endoscopic remission (defined as endoscopic subscore = 0) at Week 14.
PF 06480605 trough concentrations during the induction period through Week 14.
Change from screening in fecal calprotectin during the induction period through Week 14.
Change from baseline in hsCRP during the induction period through Week 14.
Change from baseline in serum sTL1A during the induction period through Week 14.
Incidence of development of anti drug antibodies (ADAs) and neutralizing antibodies (NAbs) during the induction period through Week 14.
Proportion of participants achieving sustained clinical remission (ie, clinical remission at both Week 14 and Week 56).
Proportion of participants achieving remission (FDA definition 1 - defined as endoscopic subscore = 0 or 1, stool frequency subscore = 0, and rectal bleeding subscore = 0) at Week 56.
Proportion of participants achieving sustained remission FDA definition 1 (ie, remission FDA definition 1 at both Week 14 and Week 56).
Proportion of participants achieving remission (FDA definition 2 - defined as endoscopic subscore = 0 or 1, =1 point decrease from baseline to achieve a stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0) at Week 56.
Proportion of participants achieving sustained remission FDA definition 2 (ie, remission FDA definition 2 at both Week 14 and Week 56).
Proportion of participants achieving endoscopic improvement (defined as endoscopic subscore = 0 or 1) at Week 56.
Proportion of participants achieving sustained endoscopic improvement (ie, endoscopic improvement at both Week 14 and Week 56).
Proportion of participants achieving endoscopic remission (defined as endoscopic sub score = 0) at Week 56.
Proportion of participants achieving sustained endoscopic remission (ie, endoscopic remission at both Week 14 and Week 56).
PF 06480605 concentration from Week 14 through the End of Study Visit.
Change from Week 14 in fecal calprotectin during the chronic therapy period through the End of Study Visit.
Change from Week 14 in hsCRP during the chronic therapy period through the End of Study Visit.
Change from week 14 in serum sTL1A during the chronic therapy period through the End of Study Visit.
Incidence of development of anti drug antibodies (ADAs) and neutralizing antibodies (NAbs) from Week 14 through the End of Study Visit.

Secondary ID(s)

2019-002698-74-ES

B7541007

129188

Source(s) of Monetary Support

Pfizer Inc

Ethics review

Status: Approved
Approval date: 03/06/2020
Contact: