Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Study To Assess The Efficacy And Safety Of PF-04236921 In Subjects With Crohn's Disease Who Failed Anti-TNF Therapy (ANDANTE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01287897
First received: January 31, 2011
Last updated: December 14, 2015
Last verified: December 2015
  Purpose
This is a proof of concept study to determine the efficacy and safety of a monoclonal antibody with three doses versus placebo. Subjects will be randomized to a treatment and the dose will be delivered subcutaneously twice, 4 weeks apart. All subjects will have moderate to severe refractory Crohn's Disease.

Condition Intervention Phase
Crohn's Disease
Drug: PF-04236921 SC injection
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-04236921 In Subjects With Crohn's Disease Who Are Anti-tnf Inadequate Responders (Andante)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • The Crohn's Disease Activity Index (CDAI)-70 Response Rate at Week 8 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score greater than or equal to (>=) 0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

  • The CDAI-70 Response Rate at Week 8 in Participants Who Received Placebo and PF-04236921 200 mg [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 8 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 1, that will yield different estimates for placebo for the two different models.

  • The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

  • The CDAI-70 Response Rate at Week 12 in Participants Who Received Placebo and PF-04236921 200 mg [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 3, that will yield different estimates for placebo for the two different models.


Secondary Outcome Measures:
  • The CDAI-70 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [ Time Frame: Baseline and Weeks 2, 4, 6, and 10 ] [ Designated as safety issue: No ]
    CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

  • The CDAI-70 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg [ Time Frame: Baseline and Weeks 2, 4, 6, and 10 ] [ Designated as safety issue: No ]
    CDAI-70 response was defined as a decrease in CDAI score of 70 or greater from baseline. The proportions of participants with CDAI-70 response were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 5, that will yield different estimates for placebo for the two different models.

  • The CDAI Remission Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [ Time Frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
    CDAI remission rate was defined as an absolute CDAI score less than (<) 150. The proportions of participants with CDAI remission were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

  • The CDAI Remission Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg [ Time Frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
    CDAI remission rate was defined as an absolute CDAI score <150. The proportions of participants with CDAI remission were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 7, that will yield different estimates for placebo for the two different models.

  • The CDAI-100 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [ Time Frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
    CDAI-100 response was defined as a decrease in CDAI score of 100 or greater from baseline. The proportions of participants with CDAI-100 response at Week 12 were compared between placebo and PF-04236921 10 mg/50 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

  • The CDAI-100 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg [ Time Frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
    CDAI-100 response was defined as a decrease in CDAI score of 100 or greater from baseline. The proportions of participants with CDAI-100 response at Week 12 were compared between placebo and PF-04236921 200 mg. CDAI is used to quantify the symptoms of patients with Crohn's Disease. CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit. Many clinical trials use the endpoint for response as a 70 or greater point decrease in CDAI and clinical remission is often defined as a CDAI score below 150. The Outcome included a Generalized linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 9, that will yield different estimates for placebo for the two different models.

  • Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg [ Time Frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
    CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit, and higher score indicate more severe disease. The Outcome included a Linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference).

  • Change From Baseline in CDAI Score Over Time in Participants Who Received Placebo and PF-04236921 200 mg [ Time Frame: Baseline and Weeks 2, 4, 6, 8, 10, and 12 ] [ Designated as safety issue: No ]
    CDAI evaluates 8 Crohn's disease-related variables during a 1-week assessment period, yielding a composite score >=0 and without an upper limit, and higher score indicate more severe disease. The Outcome included a Linear mixed model analyses which incorporated longitudinal data for each subject, and the same model is used for estimate (least squares mean) and statistical analysis (mean difference). Since the inputs in the model included different Analysis Population than in Outcome Measure 11, that will yield different estimates for placebo for the two different models.

  • Percentages of Participants With Confirmed Positive Anti-drug Antibodies (ADAs) [ Time Frame: At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40 ] [ Designated as safety issue: Yes ]
    The percentage of participants with confirmed positive ADA was summarized for each treatment arm. ADA positive was defined as ADA titer defined as ADA titer (ie, the reciprocal of the highest dilution that gives a value equivalent to the cut point of the assay) >= 4.32.

  • Percentages of Participants With Confirmed Positive Neutralizing Antibodies (NAbs) [ Time Frame: At baseline (Day 1) and at Weeks 4, 8, 12, 16, 24, 32 and 40 ] [ Designated as safety issue: Yes ]
    The percentage of participants with confirmed positive NAbs was summarized for each treatment arm. Only ADA positive samples were analyzed for Nab. A multi-tiered approach was utilized to detect NAbs. NAb serum samples were screened at tier one, and those found presumptively NAb positive was further tested with the confirmatory assay (tier two). The percentage of subjects with confirmed positive NAbs was summarized for each treatment.

  • Serum PF-04236921 Concentration Over Time [ Time Frame: Day 1 (predose), and at Weeks 2, 4 (Day 28, predose), 8, 10, 12, 16, 20, 24, 28, 32, 36, and 40 ] [ Designated as safety issue: No ]
  • Number of Participants Who Withdrew From the Study Due to Treatment-emergent Adverse Events (AEs) [ Time Frame: Induction period: from Week 0 (Day 1) through Week 12; follow-up period: from Week 12 (or discontinuation from the induction period) through last subject visit (up to 28 weeks after completion of or discontinuation from the 12-week induction period) ] [ Designated as safety issue: Yes ]
    An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. Treatment-emergent were events between first dose of treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.


Enrollment: 250
Study Start Date: February 2011
Study Completion Date: February 2015
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo- SC injection Drug: PF-04236921 SC injection
Placebo delivered SC, 2 doses separated by 4 weeks
Experimental: Drug Dose level 1 - SC injection Drug: PF-04236921 SC injection
Drug dose level 1 delivered SC, 2 doses separated by 4 weeks
Experimental: Drug Dose level 2 - SC injection Drug: PF-04236921 SC injection
Drug dose level 2 delivered SC, 2 doses separated by 4 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have failed or are intolerant to anti TNFs
  • hsCRP greater or equal to 5.0 mg/L
  • Ulcerations demonstrated by colonoscopy as defined by SES CD assessment performed within 8 weeks of study entry (screening) and able to retrospectively complete the SES-CD or colonoscopy performed during screening

Exclusion Criteria:

  • Pregnant or breastfeeding women
  • Crohn's Disease with active fistulae or abscess
  • History of diverticulitis or symptomatic diverticulosis
  • Abnormality in hematology or chemistry profiles at screening
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01287897

  Show 193 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01287897     History of Changes
Other Study ID Numbers: B0151003  2010-023034-23  ANDANTE 
Study First Received: January 31, 2011
Results First Received: September 14, 2015
Last Updated: December 14, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Crohn's Disease
safety
efficacy
pharmacokinetics
pharmacodynamics
Crohn's Disease Activity Index (CDAI)

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on December 09, 2016