Clinical trial NCT02840721: Safety, Efficacy, and Tolerability Study of PF-06480605 in Subjects With Moderate to Severe Ulcerative Colitis.
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colitis, Ulcerative
Lead sponsor: Telavant, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2016-07-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: This is a Phase 2a, single arm, two-stage study in subjects with moderate to severe ulcerative colitis. Subjects will receive 500 mg of PF-06480605 intravenously every 2 weeks for a total of 7 doses. Blood, stool, and tissue samples will be collected at various time points throughout the study to evaluate safety, tolerability, efficacy, pharmacokinetics, and immunogenicity. Duration of participation for subjects will be approximately 8 months.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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
  * Biologics including anti-TNF inhibitors as described: Infliximab, Adalimumab, or Golimumab within 8 weeks prior to baseline
  * Anti-integrin inhibitors (eg, vedolizumab) within 12 weeks prior to baseline
  * Other investigational procedures or products, or live attenuated vaccine within 30 days prior to baseline.
* Current or history (within 2 years) of serious psychiatric disease or alcohol or drug abuse

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events, Serious Adverse Events, and Who Withdrew Due to Adverse Events
timeFrame: Day 1 up to final onsite visit (Week 26)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Day 1 up to final onsite visit (Week 26)
measure: Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
timeFrame: Baseline up to final onsite visit (Week 26)
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria
timeFrame: Baseline up to final onsite visit (Week 26)
measure: Percentage of Participants Achieving Endoscopic Improvement at Week 14, Based on Uniformly Minimum-Variance Unbiased Estimator (UMVUE) - Per Protocol Analysis Set
timeFrame: Week 14
Secondary outcomes:
measure: Percentage of Participants Achieving Remission at Week 14 - Full Analysis Set
timeFrame: Week 14
measure: Percentage of Participants Achieving Remission at Week 14 - Per Protocol Analysis Set
timeFrame: Week 14
measure: Percentage of Participants Achieving Endoscopic Remission at Week 14 - Full Analysis Set
timeFrame: Week 14
measure: Maximum Serum Concentration (Cmax) of PF-06480605
timeFrame: 30 minutes pre-dose and 1 hour post-dose on Day 85
measure: Average Serum Concentration (Cav) of PF-06480605
timeFrame: 30 minutes pre-dose and 1 hour post-dose on Day 85
measure: Lowest Serum Concentration (Cmin) of PF-06480605
timeFrame: 30 minutes pre-dose and 1 hour post-dose on Day 85
measure: Area Under the Concentration-time Profile From Time Zero to Time Tau (AUCtau) of PF-06480605
timeFrame: 30 minutes pre-dose and 1 hour post-dose on Day 85
measure: Percentage of Participants Who Developed Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
timeFrame: Day 1 up to final onsite visit (Week 26)
measure: Change From Baseline in Fecal Calprotectin
timeFrame: Baseline, Weeks 2, 8, 12 and 26
measure: Change From Baseline in High Sensitivity C-reactive Protein (HsCRP)
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, and 26
measure: Change From Baseline in Serum Total Soluable Tumor Necrosis Factor-like Ligand 1A (sTL1A)
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, and 26
Other outcomes:
Locations:
city: Aventura
country: United States
facility: Surgery Center of Aventura
state: Florida
city: North Miami Beach
country: United States
facility: Venture Ambulatory Surgical Center
state: Florida
city: Pembroke Pines
country: United States
facility: FQL Research, LLC
state: Florida
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Chestnut Hill
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Great Neck
country: United States
facility: NYU Langone Long Island Clinical Research Associates
state: New York
city: Great Neck
country: United States
facility: NYU Langone Nassau Gastroenterology Associates
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital-Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Wauwatosa
country: United States
facility: Allegiance Research Specialists, LLC
state: Wisconsin
city: Leuven
country: Belgium
facility: UZ Leuven (University Hospital Leuven) - Pharmacy Clinical Trials
city: Leuven
country: Belgium
facility: UZ Leuven (University Hospital Leuven) - Radiology Department
city: Leuven
country: Belgium
facility: UZ Leuven (University Hospital Leuven), Campus Gasthuisberg
city: Catanzaro
country: Italy
facility: AOU Mater Domini - Univ."Magna Graecia" di Catanzaro - Campus Venuta - U.O Fisiopatologia Digestiva
state: CZ
city: Rozzano
country: Italy
facility: ISTITUTO CLINICO HUMANITAS Sezione Autonoma di Malattie Infiammatorie Croniche Intestinali
state: Milan (MI)
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
state: RM
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Amsterdam
country: Netherlands
facility: Academic Medical Center, Apotheek-Kenniscentrum Geneesmiddelenonderzoek
state: North Holland
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre, Department of Radiology
state: North Holland
city: Amsterdam
country: Netherlands
facility: Academic Medical Centre, Dept. of Gastroenterology
state: North Holland
city: Bialystok
country: Poland
facility: SPZOZ WSzZ im. Jedrzeja. Sniadeckiego W Bialymstoku Oddzial Chorob Wewnetrznych i Gastroenterologii
city: Bydgoszcz
country: Poland
facility: Centrum Endoskopii Zabiegowej, Poradnia Chorob Jelitowych Szpital Uniwersytecki nr 2 im Jana Biziela
city: Krakow
country: Poland
facility: Piotr Walczak Gabinet Endoskopii Przewodu Pokarmowego
city: Lodz
country: Poland
facility: SANTA FAMILIA Centrum Badan Profilaktyki i Leczenia
city: Sopot
country: Poland
facility: Endoskopia Sp. z.o.o.
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.