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PF-04236921

Phase 2

Crohn's Disease | Monoclonal antibody | Immunology |Pfizer, Inc.|Last Updated: Jan 12, 2024

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindPLACEBO_CONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment441
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01345318B0151005 Open-Label Extension StudyPHASE2 COMPLETED 191Jun 1, 2011Mar 1, 2016Jan 12, 2024127 United States, Australia +14
NCT01287897A Study To Assess The Efficacy And Safety Of PF-04236921 In Subjects With Crohn's Disease Who Failed Anti-TNF TherapyPHASE2 COMPLETED 250Feb 1, 2011Feb 1, 2015Jan 21, 2016193 United States, Australia +16
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Study Endpoints
Primary Endpoints
Number of Participants With On-Treatment Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
Baseline up to Week 48

An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Lack of efficacy was reported as an AE when it was associated with a SAE. An AE was considered treatment emergent if it started for the first time in a participant on or after the first day of active treatment, or the event started before the first day of active treatment but increased in severity during active treatment. AEs included both SAEs and non-serious AEs.

Percentage of Participants Developing Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
At Baseline and Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72 and 76.

Samples were analyzed using the semi-quantitative electrochemiluminescent (ECL) immunoassay method, a validated analytical method in compliance with sponsor's standard operating procedures. ADA positive is defined as ADA titer greater than or equal to (\>=) 4.32. Any positive ADA sample was further tested for NAbs.

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
Baseline and Week 8

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
Baseline and Week 8

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
Baseline and Week 12

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
Baseline and Week 12

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 Endpoints
The CDAI-70 Response Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
Baseline and Weeks 2, 4, 6, and 10
The CDAI-70 Response Rate Over Time in Participants Who Received Placebo and PF-04236921 200 mg
Baseline and Weeks 2, 4, 6, and 10
The CDAI Remission Rate Over Time in Participants Who Received Placebo, PF-04236921 10 mg and PF-04236921 50 mg
Baseline and Weeks 2, 4, 6, 8, 10, and 12
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Open-label TreatmentEXPERIMENTAL -
Placebo- SC injectionPLACEBO_COMPARATOR -
Drug Dose level 1 - SC injectionEXPERIMENTAL -
Drug Dose level 2 - SC injectionEXPERIMENTAL -
Interventions
NameTypeDescription
PF-04236921BIOLOGICALSubjects entering this study will be given a 50 mg SC dose at baseline and then every 8 weeks through Week 40.
PF-04236921 SC injectionDRUGPlacebo delivered SC, 2 doses separated by 4 weeks
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Eligibility Criteria
Age Range18 Years — 75 Years
SexALL
Healthy VolunteersNo
Study Sites127

Inclusion Criteria: * Subjects previously enrolled in study B0151003 and completed the blinded 84 day (12 week) induction period. * Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. * Women of childbearing potential, who...

Countries:United StatesAustraliaBelgiumBrazilCanadaCzechiaDenmarkFranceGermanyHungaryIrelandIsraelItalyNew ZealandSwitzerlandUnited KingdomGreeceRomania
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