Efficacy, Safety and Tolerability of PF-06687234 as Add-on Therapy to Infliximab in Active UC Subjects Not in Remission.

NCT03269695 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: B75810022017-002108-28BUILD UC
• Study Type: interventional
• Target: 20
• Locations: 10 countries
• Sites: 34

Brief Summary

The purpose of this study is to determine if PF-06687234 is effective and safe as add-on therapy to infliximab in subjects with active ulcerative colitis who are not in remission.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (9)

• Percentage of Participants in Modified Clinical Remission at Week 12 (Traditional Endoscopic Subscore <=1, Observed Cases)

  The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) \<=2, no individual subscore \>1, traditional endoscopic subscore \<=1 (where mild friability was scored as of 1; moderate or severe friability was scored as 2) and rectal bleeding subscore=0. Participants with missing values were handled by observed case approach (the missing data were used as is). The percentage of participants achieving modified clinical remission was calculated based on the number of participants with observed data.

  Week 12

• Percentage of Participants in Modified Clinical Remission at Week 12 (Traditional Mayo Endoscopic Subscore <=1, Treatment Failure Approach)

  The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) \<=2, no individual subscore \>1, traditional endoscopic subscore \<=1 (where mild friability was scored as of 1; moderate or severe friability was scored as 2) and rectal bleeding subscore=0. Participants with missing values were handled by treatment failure approach (participants who had missing value for any reasons were considered as treatment failures).

  Week 12

• Percentage of Participants in Modified Clinical Remission at Week 12 (Modified Mayo Endoscopy Subscore = 0 or 1, Observed Cases)

  The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) with endoscopic subscore = 0 or 1 (where any friability was scored as a mayo endoscopic subscore of 2), stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0. Participants with missing values were handled by observed case approach (the missing data were used as is). The percentage of participants achieving modified clinical remission was calculated based on the number of participants with observed data.

  Week 12

• Percentage of Participants in Modified Clinical Remission at Week 12 (Modified Mayo Endoscopy Subscore = 0 or 1, Treatment Failure Approach)

  The Mayo score consists of 4 subscores (Endoscopic, stool frequency, rectal bleeding and Physician's global assessment \[PGA\]), each graded 0 to 3 with the higher score indicating more severe disease activity. Modified clinical remission is defined as a modified total Mayo Score (total Mayo score excluding the PGA subscore) with endoscopic subscore = 0 or 1 (where any friability was scored as a mayo endoscopic subscore of 2), stool frequency subscore = 0 or 1, and rectal bleeding subscore = 0. Participants with missing values were handled by treatment failure approach (participants who had missing value for any reasons were considered as treatment failures).

  Week 12

• Number of Participants With Treatment-Emergent Adverse Events (AEs; All Causalities)

  Treatment-emergent AEs are those with initial onset or that worsen in severity after the first dose of the study medication. All AEs in the table below were treatment-emergent AEs. An serious adverse event (SAE) is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event that may jeopardize the participant or may require intervention to prevent one of the other AE outcomes. Severe AEs were defined as AEs that interfered significantly with participant's usual function. Both SAEs and severe AEs were according to the investigator's assessment.

  Baseline (Day 1) through and including a minimum of 28 calendar days after the last administration of the investigational products (22 weeks in total)

• Number of Participants With Treatment-Emergent AEs (Treatment Related)

  Treatment-emergent AEs are those with initial onset or that worsen in severity after the first dose of the study medication. All AEs in the table below were treatment-emergent AEs. An SAE is any untoward medical occurrence at any dose that: results in death; is life threatening (immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); results in congenital anomaly/birth defect; or that is considered to be an important medical event that may jeopardize the participant or may require intervention to prevent one of the other AE outcomes. Severe AEs were defined as AEs that interfered significantly with participant's usual function. Both SAEs and severe AEs were according to the investigator's assessment. Treatment-related AEs were also determined by the investigator.

  Baseline (Day 1) through and including a minimum of 28 calendar days after the last administration of the investigational products (22 weeks in total)

• Number of Participants With Laboratory Test Abnormalities Without Regard to Baseline Abnormality

  The laboratory tests as defined in the protocol, including hematology, chemistry, urinalysis and other, were performed. Baseline was defined as the last measurement prior to first dosing (Day 1).

  From baseline through Week 16

• Number of Participants With Categorical Vital Signs

  Single sitting blood pressure (BP), pulse rate, and temperature were measured. At Day 1 and Week 1, BP and pulse were collected approximately 30 minutes prior to dosing, approximately 30 minutes post dosing and approximately 1 hour post dosing. For participants with no safety issues (eg, severe injection site reactions, severe elevations BP and/or pulse), BP and pulse were collected approximately 30 minutes prior to dosing and approximately 30 minutes post dosing from Weeks 2-16. Vital signs were analyzed as per pre-specified categories.

  From baseline through Week 16

• Number of Participants With Categorical Electrocardiogram (ECG) Data

  Twelve (12) lead ECGs were collected. All scheduled ECGs were performed after the participants had rested quietly for at least 10 minutes in a supine position. When the timing of these measurements coincided with a blood collection, the ECG was obtained prior to the nominal time of the blood collection, blood pressure, and pulse rate. ECG data were analyzed as per pre-specified categories. PR=pulse rate; QTc=QT interval corrected for heart rate; QTcF=QTc corrected using Fridericia's formula.

  From baseline through Week 16

Secondary Outcomes (9)

• Percentage of Participants With Endoscopic Improvement at Week 12 ( Observed Cases)

  Week 12

• Percentage of Participants With Endoscopic Improvement at Week 12 ( Treatment Failure Approach)

  Week 12

• Percentage of Participants Achieving Geboes Index Remission at Week 12 (Observed Cases)

  Week 12

• Change From Baseline in Robart's Histology Index at Week 12 (Observed Cases)

  Week 12

• Percentage of Participants With a Clinical Response at Week 12 (Observed Cases)

  Week 12

Study Arms (2)

PF-06687234

EXPERIMENTAL

PF-06687234 subcutaneous (SC) weekly (QW) x 12 doses

Drug: PF-06687234

Placebo

PLACEBO COMPARATOR

PF-06687234 matched Placebo SC QW x 12 doses

Drug: Placebo

Interventions

PF-06687234 DRUG

SC QW

Also known as: Investigational product

PF-06687234

Placebo DRUG

SC QW

Also known as: PF-06687234 matched placebo

Placebo

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 and/or female subjects 18 years to 75 years of age and weight \> 40 kg at the time of informed consent.
• A diagnosis of active UC (histologic) for 4 months.
• Subjects with active UC as defined by (via screening endoscopy) a total Mayo Score of 4 or more but 9 or less and an endoscopic subscore of 2.or more.
• UC extending at least 15 cm proximal to the anal verge at the time of the screening endoscopy.
• Must be on a stable dose 5-10 mg/kg of Remicade, Inflectra, or Remsima for a minimum of 14 weeks with no anticipation of need for change in infliximab treatment regimen throughout the study
• Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use two methods of contraception (at least one of which is considered as highly effective) throughout the study and until the Week 16 visit

You may not qualify if:

• Subjects with a diagnosis or documented history of total colectomy and/or pouchitis, indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis, or clinical findings suggestive of Crohn's disease.
• Subjects need for surgery or with major elective surgery scheduled during the study.
• Subjects with extensive colitis for at least 8 years who have not had a colonoscopy with surveillance biopsies within 2 years prior to baseline.
• Subjects with history of or at screening endoscopy, biopsy documented colonic dysplasia or neoplasia.
• Subjects who require infliximab dosing interval other than every 6 weeks or every 8 weeks.
• Subjects displaying clinical signs of fulminant colitis or toxic megacolon, with primary sclerosing cholangitis, known colonic stricture, history of colonic, small bowel obstruction or resection, with history of or current colonic or small bowel stoma.
• Cyclic neutropenia, thrombocytopenia, lymphopenia, leukopenia or history of chronic anemia.
• Presence of active enteric infection.
• Known history of human immunodeficiency virus (HIV) based on documented history with positive serological test, or positive HIV serologic test.
• Presence of transplanted organ.
• Anticipated need for any live vaccine.
• Class III or Class IV heart failure.
• Acute coronary syndrome and any history of cerebrovascular disease.
• Subjects with current, or a history of QT prolongation.
• Subjects receiving the following therapies within the designated time period:

Sponsors & Collaborators

• Pfizer: lead

Study Sites (34)

Dothan Surgery Center

Dothan, Alabama, 36301, United States

Location

Gut PC, dba Digestive Health Specialists of the Southeast

Dothan, Alabama, 36305, United States

Location

Emory Investigational Drug Services

Atlanta, Georgia, 30322, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Chevy Chase Endoscopy Center

Chevy Chase, Maryland, 20815, United States

Location

MGG Group Co., Inc., Chevy Chase Clinical Research

Chevy Chase, Maryland, 20815, United States

Location

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, 48047, United States

Location

East Valley Endoscopy

Grand Rapids, Michigan, 49546, United States

Location

Eastside Endoscopy Center

Macomb, Michigan, 48044, United States

Location

Eastside Endoscopy Center

Saint Clair Shores, Michigan, 48041, United States

Location

Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center

Wyoming, Michigan, 49519, United States

Location

Allegiance Research Specialists

Wauwatosa, Wisconsin, 53226, United States

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Eastern Health-Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

St. Vincent's Hospital, Melbourne

Fitzroy, Victoria, 3065, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

St John Of God Health Care Inc. Trading as St. John of God Subiaco Hospital

Subiaco, Western Australia, 6008, Australia

Location

CHC Montlegia

Liège, 4000, Belgium

Location

Universitaetsklinikum Schleswig-Holstein Campus Kiel

Kiel, 24105, Germany

Location

The Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

ASST Rhodense - Ospedale di Circolo di Rho

Rho, Milano, 20017, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, 00168, Italy

Location

King Abdulaziz University Hospital

Jeddah, 22252, Saudi Arabia

Location

King Abdullah International Medical Research Center

Riyadh, 11426, Saudi Arabia

Location

King Khalid University Hospital

Riyadh, 11472, Saudi Arabia

Location

CHC "Dr Dragisa Misovic-Dedinje"

Belgrade, 11000, Serbia

Location

Clinical Hospital Center Zvezdara - Clinic for Gastroenterology and Hepatology

Belgrade, 11000, Serbia

Location

The Catholic University of Korea, St. Vincent's Hospital

Gyeonggi-do, 16247, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Mersin Universitesi Tip Fakultesi Hastanesi

Mersin, 33110, Turkey (Türkiye)

Location

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

Limitations and Caveats

The study was terminated after an interim analysis, due to efficacy being considered unlikely to meet the projected target.

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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2017
• First Posted: September 1, 2017
• Study Start: December 20, 2017
• Primary Completion: January 7, 2021
• Study Completion: January 7, 2021
• Last Updated: December 28, 2021
• Results First Posted: December 28, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share

Locations

SA (3); DE (1); KR (2); IT (3); TU (1); US (14); AU (6); BE (1); IL (1); SE (2)