Safety, Efficacy, and Tolerability Study of PF-06480605 in Subjects With Moderate to Severe Ulcerative Colitis.

NCT02840721 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: B7541002TUSCANY2016-001158-16
• Study Type: interventional
• Target: 50
• Locations: 6 countries
• Sites: 28

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of PF-06480605 in subjects with moderate to severe ulcerative colitis.

Conditions

Colitis, Ulcerative

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events

  An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. A serious AE (SAE) was any untoward medical occurrence at any dose that (1) resulted in death; (2) was life-threatening (immediate risk of death); (3) required inpatient hospitalization or prolongation of existing hospitalization; (4) resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); (5) resulted in congenital anomaly/birth defect. A treatment-emergent AE (TEAE) was defined as an event that emerged during treatment having been absent pre-treatment, or worsened relative to the pre-treatment state. Causality to study treatment was determined by the investigator.

  Day 1 up to final onsite visit (Week 26)

• Number of Participants With Laboratory Abnormalities

  The following parameters were evaluated: hematology (hemoglobin, hematocrit, erythrocytes, erythrocyte mean corpuscular volume, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time, and prothrombin time), clinical chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, glucose, and creatine kinase), and urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, nitrite, leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and bacteria).

  Day 1 up to final onsite visit (Week 26)

• Number of Participants With Vital Signs Data Meeting Pre-specified Criteria

  Vital signs evaluation included sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse rate. Sitting blood pressure was measured with the participant's arm supported at the level of the heart, and recorded to the nearest millimeters of mercury (mm Hg). The same size BP cuff which had been properly sized and calibrated was used to measure BP each time. Number of participants with vital signs data meeting pre-specified criteria is presented.

  Baseline up to final onsite visit (Week 26)

• Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria

  All scheduled 12-lead ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Number of participants with ECG data meeting pre-specified criteria is presented.

  Baseline up to final onsite visit (Week 26)

• Percentage of Participants Achieving Endoscopic Improvement at Week 14, Based on Uniformly Minimum-Variance Unbiased Estimator (UMVUE) - Per Protocol Analysis Set

  Endoscopic improvement at Week 14 was defined as Mayo endoscopic sub-score of 0 or 1, and without friability. The Mayo scoring system was used to assess ulcerative colitis activity, and it ranges from 0 to 12, calculated as sum of 4 sub-scores, with higher scores indicating more severe disease. The 4 sub-scores are stool frequency (0=normal number of stools; 1=1 to 2 stools more than normal; 2=3 to 4 stools more than normal; 3= 5 or more stools more than normal); rectal bleeding (0=no blood seen; 1=streaks of blood with stools less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes); findings on endoscopy (0=normal or inactive disease; 1=mild disease \[erythema, decreased vascular pattern, mild friability\]; 2=moderate disease \[marked erythema, lack of vascular pattern, friability, erosions\]; 3=severe disease \[spontaneous bleeding, ulceration\]); and physician's global assessment (0=normal; 1=mild disease; 2=moderate disease; 3=severe disease).

  Week 14

Secondary Outcomes (11)

• Percentage of Participants Achieving Remission at Week 14 - Full Analysis Set

  Week 14

• Percentage of Participants Achieving Remission at Week 14 - Per Protocol Analysis Set

  Week 14

• Percentage of Participants Achieving Endoscopic Remission at Week 14 - Full Analysis Set

  Week 14

• Maximum Serum Concentration (Cmax) of PF-06480605

  30 minutes pre-dose and 1 hour post-dose on Day 85

• Average Serum Concentration (Cav) of PF-06480605

  30 minutes pre-dose and 1 hour post-dose on Day 85

Study Arms (1)

PF-06480605

EXPERIMENTAL

PF-06480605 500 mg IV Q2W X 7 doses

Drug: PF-06480605

Interventions

PF-06480605 DRUG

PF-06480605 500 mg IV Q2W x 7 Doses

PF-06480605

Eligibility Criteria

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

You may qualify if:

• Male or female subjects between ≥ 18 and ≤ 75 years of age at the time of informed consent
• Male subjects able to father children and female subjects of childbearing potential must agree to use two highly effective methods of contraception throughout the study and until the Week 26 visit
• Diagnosis of ulcerative colitis for ≥ 4 months
• Subjects with moderate to severe active ulcerative colitis as defined by screening colonoscopy with total Mayo score of ≥ 6, with rectal bleeding subscore of ≥ 1, and an endoscopic subscore of ≥ 2 on the Mayo
• Active disease beyond the rectum (\> 15 cm of active disease at the screening colonoscopy)
• Must have inadequate response to, loss of response to, or intolerance to at least one conventional therapy for ulcerative colitis such as: Steroids; Immunosuppressants (AZA, 6-MP, or MTX); Anti -TNF inhibitors (eg, infliximab, adalimumab, or golimumab); Anti-integrin inhibitors (eg, vedolizumab).
• Subjects currently receiving the following treatment are eligible provided they have been on stable doses of Oral 5-ASA or sulfasalazine for at least 4 weeks prior to baseline; oral corticosteroids stable dose for at least 2 weeks prior to baseline; 6-MP or AZA stable dose for 8 weeks prior to baseline.

You may not qualify if:

• Diagnosis of indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, microscopic colitis or Crohn's Disease. Subjects with clinical findings suggestive of Crohn's disease (eg, fistulae, granulomas on biopsy) are also excluded.
• Subjects with colonic dysplasia or neoplasia, toxic megacolon, primary sclerosing cholangitis, known colonic stricture, history of colonic or small bowel stoma, history of colonic or small bowel obstruction or resection
• Presence of active enteric infections (positive stool culture and sensitivity)
• Known history of HIV based on documented history with positive serological test, or positive HIV serologic test at screening
• Presence of a transplanted organ
• Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence);
• Acute coronary syndrome (eg., myocardial infarction, unstable angina pectoris);
• Any history of cerebrovascular disease within 24 weeks before screening;
• Subject with current or a history of QT prolongation
• Class III or Class IV heart failure
• Prior evidence of liver injury or toxicity due to methotrexate
• Abnormality in hematology and/or chemistry profiles during screening (as detailed in the protocol)
• Subjects receiving the following therapies within the designated time period:
• \> 9 mg/day of oral budesonide or \>20 mg/day prednisone or equivalent 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

Sponsors & Collaborators

• Telavant, Inc.: lead
• Pfizer: collaborator

Study Sites (28)

Surgery Center of Aventura

Aventura, Florida, 33180, United States

Location

Venture Ambulatory Surgical Center

North Miami Beach, Florida, 33162, United States

Location

FQL Research, LLC

Pembroke Pines, Florida, 33027, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Chestnut Hill, Massachusetts, 02467, United States

Location

NYU Langone Long Island Clinical Research Associates

Great Neck, New York, 11021, United States

Location

NYU Langone Nassau Gastroenterology Associates

Great Neck, New York, 11021, United States

Location

New York Presbyterian Hospital-Weill Cornell Medical College

New York, New York, 10021, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

New York Presbyterian Hospital

New York, New York, 10065, United States

Location

Allegiance Research Specialists, LLC

Wauwatosa, Wisconsin, 53226, United States

Location

UZ Leuven (University Hospital Leuven) - Pharmacy Clinical Trials

Leuven, 3000, Belgium

Location

UZ Leuven (University Hospital Leuven) - Radiology Department

Leuven, 3000, Belgium

Location

UZ Leuven (University Hospital Leuven), Campus Gasthuisberg

Leuven, 3000, Belgium

Location

AOU Mater Domini - Univ."Magna Graecia" di Catanzaro - Campus Venuta - U.O Fisiopatologia Digestiva

Catanzaro, CZ, 88100, Italy

Location

ISTITUTO CLINICO HUMANITAS Sezione Autonoma di Malattie Infiammatorie Croniche Intestinali

Rozzano, Milan (MI), 20089, Italy

Location

Policlinico Universitario Campus Biomedico

Roma, RM, 00128, Italy

Location

Academic Medical Center, Apotheek-Kenniscentrum Geneesmiddelenonderzoek

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Academic Medical Centre, Department of Radiology

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Academic Medical Centre, Dept. of Gastroenterology

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

SPZOZ WSzZ im. Jedrzeja. Sniadeckiego W Bialymstoku Oddzial Chorob Wewnetrznych i Gastroenterologii

Bialystok, 15-950, Poland

Location

Centrum Endoskopii Zabiegowej, Poradnia Chorob Jelitowych Szpital Uniwersytecki nr 2 im Jana Biziela

Bydgoszcz, 85-168, Poland

Location

Piotr Walczak Gabinet Endoskopii Przewodu Pokarmowego

Krakow, 31-009, Poland

Location

SANTA FAMILIA Centrum Badan Profilaktyki i Leczenia

Lodz, 90-302, Poland

Location

Endoskopia Sp. z.o.o.

Sopot, 81-756, Poland

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Related Publications (1)

• Danese S, Klopocka M, Scherl EJ, Romatowski J, Allegretti JR, Peeva E, Vincent MS, Schoenbeck U, Ye Z, Hassan-Zahraee M, Rath N, Li G, Neelakantan S, Banfield C, Lepsy C, Chandra DE, Hung KE. Anti-TL1A Antibody PF-06480605 Safety and Efficacy for Ulcerative Colitis: A Phase 2a Single-Arm Study. Clin Gastroenterol Hepatol. 2021 Nov;19(11):2324-2332.e6. doi: 10.1016/j.cgh.2021.06.011. Epub 2021 Jun 12.

  PMID: 34126262 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2016
• First Posted: July 21, 2016
• Study Start: October 26, 2016
• Primary Completion: May 31, 2018
• Study Completion: August 30, 2018
• Last Updated: October 23, 2023
• Results First Posted: June 19, 2019

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share

Locations

BE (3); KR (2); IT (3); NL (3); PL (5); US (12)