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

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ClinicalTrials.gov Identifier: NCT02840721
Recruitment Status : Completed
First Posted : July 21, 2016
Last Update Posted : February 27, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: PF-06480605 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 26, 2016
Actual Primary Completion Date : May 31, 2018
Actual Study Completion Date : August 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-06480605
PF-06480605 500 mg IV Q2W X 7 doses
Drug: PF-06480605
PF-06480605 500 mg IV Q2W x 7 Doses




Primary Outcome Measures :
  1. Incidence of intolerability treatment-related AEs [ Time Frame: Baseline Week 0 through Week 26 ]
  2. Incidence, severity, and causal relationship of treatment emergent AEs (TEAEs), withdrawals due to AEs, and SAEs [ Time Frame: Baseline Week 0 through Week 26 ]
  3. Incidence and magnitude of abnormal laboratory findings [ Time Frame: Baseline Week 0, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 ]
  4. Abnormal and clinically relevant changes in vital signs, blood pressure (BP) and electrocardiogram (ECG) parameters [ Time Frame: Baseline Week 0, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 ]
  5. Evaluate efficacy of PF-06480605 in induction of endoscopic improvement [ Time Frame: Week 14 ]
    Assessed by Mayo endoscopic subscore


Secondary Outcome Measures :
  1. Evaluate efficacy of PF-06480605 in induction of remission [ Time Frame: Week 14 ]
    Defined as total Mayo score less than or equal to 2 with no individual subscore greater than 1

  2. Change from baseline in fecal calprotectin [ Time Frame: Baseline Week 0, Weeks 2, 8, 12, 26 ]
  3. Change from baseline in high sensitivity C-reactive protein (hsCRP) [ Time Frame: Baseline Week 0, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 ]
  4. Change from baseline in total serum soluble TL1A (sTL1A) [ Time Frame: Baseline Week 0, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 ]
  5. Evaluate Peak Plasma Concentration (Cmax) of PF-06480605 [ Time Frame: Baseline Week 0, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 ]
  6. Evaluate trough plasma concentration (Ctrough) of PF-06480605 [ Time Frame: Baseline Week 0, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 ]
  7. Evaluate Area under the Curve to the end of the dosing period (AUC tau) of PF-06480605 [ Time Frame: Baseline Weeks 0, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 ]
  8. Evaluate steady-state plasma drug concentration (Cav) of PF-06480605 [ Time Frame: Baseline Week 0, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 26 ]
  9. Evaluate anti-PF-06480605 antibodies (ADA) [ Time Frame: Baseline Week 0, Weeks, 2, 4, 8, 12, 16, 20, 24, 26 ]
  10. Evaluate PF-06480605 neutralizing antibodies (NAbs) [ Time Frame: Baseline Week 0, Weeks 2, 4, 8, 12, 16, 20, 24, 26 ]
  11. Evaluate efficacy of PF-06480605 in induction of endoscopic remission [ Time Frame: Week 14 ]
    Defined as Mayo endoscopic subscore of 0



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02840721


Locations
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United States, Florida
Surgery Center of Aventura
Aventura, Florida, United States, 33180
Venture Ambulatory Surgical Center
North Miami Beach, Florida, United States, 33162
FQL Research, LLC
Pembroke Pines, Florida, United States, 33027
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Brigham and Women's Hospital
Chestnut Hill, Massachusetts, United States, 02467
United States, New York
NYU Langone Long Island Clinical Research Associates
Great Neck, New York, United States, 11021
NYU Langone Nassau Gastroenterology Associates
Great Neck, New York, United States, 11021
New York Presbyterian Hospital-Weill Cornell Medical College
New York, New York, United States, 10021
Weill Cornell Medical College
New York, New York, United States, 10021
Weill Cornell Medicine
New York, New York, United States, 10021
New York Presbyterian Hospital
New York, New York, United States, 10065
United States, Wisconsin
Allegiance Research Specialists, LLC
Wauwatosa, Wisconsin, United States, 53226
Belgium
UZ Leuven (University Hospital Leuven) - Pharmacy Clinical Trials
Leuven, Belgium, 3000
UZ Leuven (University Hospital Leuven) - Radiology Department
Leuven, Belgium, 3000
UZ Leuven (University Hospital Leuven), Campus Gasthuisberg
Leuven, Belgium, 3000
Italy
AOU Mater Domini - Univ."Magna Graecia" di Catanzaro - Campus Venuta - U.O Fisiopatologia Digestiva
Catanzaro, CZ, Italy, 88100
ISTITUTO CLINICO HUMANITAS Sezione Autonoma di Malattie Infiammatorie Croniche Intestinali
Rozzano, Milan (MI), Italy, 20089
Policlinico Universitario Campus Biomedico
Roma, RM, Italy, 00128
Korea, Republic of
Kangbuk Samsung Hospital
Seoul, Korea, Republic of, 03181
Asan Medical Center
Seoul, Korea, Republic of, 05505
Netherlands
Academic Medical Center, Apotheek-Kenniscentrum Geneesmiddelenonderzoek
Amsterdam, North Holland, Netherlands, 1105 AZ
Academic Medical Centre, Department of Radiology
Amsterdam, North Holland, Netherlands, 1105 AZ
Academic Medical Centre, Dept. of Gastroenterology
Amsterdam, North Holland, Netherlands, 1105 AZ
Poland
SPZOZ WSzZ im. Jedrzeja. Sniadeckiego W Bialymstoku Oddzial Chorob Wewnetrznych i Gastroenterologii
Bialystok, Poland, 15-950
Centrum Endoskopii Zabiegowej, Poradnia Chorob Jelitowych Szpital Uniwersytecki nr 2 im Jana Biziela
Bydgoszcz, Poland, 85-168
Piotr Walczak Gabinet Endoskopii Przewodu Pokarmowego
Krakow, Poland, 31-009
SANTA FAMILIA Centrum Badan Profilaktyki i Leczenia
Lodz, Poland, 90-302
Endoskopia Sp. z.o.o.
Sopot, Poland, 81-756
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02840721     History of Changes
Other Study ID Numbers: B7541002
TUSCANY ( Other Identifier: Alias Study Number )
2016-001158-16 ( EudraCT Number )
First Posted: July 21, 2016    Key Record Dates
Last Update Posted: February 27, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases