Crohn's Disease
Conditions
Keywords
Crohn's Disease, safety, efficacy, pharmacokinetics, pharmacodynamics, Crohn's Disease Activity Index (CDAI)
Brief summary
This is a multi-center Phase 2, open label, safety extension study in subjects with moderate to severe CD who are anti-TNF inadequate responders. Subjects eligible for this study will have completed the 12-week induction period of study B0151003 and will be enrolled as either responders or non responders.
Interventions
BIOLOGICALPF-04236921
Subjects entering this study will be given a 50 mg SC dose at baseline and then every 8 weeks through Week 40.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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 have sexual intercourse with a non surgically sterilized male partner, must agree and commit to the use highly effective methods of birth control from signing of the ICD through 26 weeks after the Final Study Evaluation or for 62 weeks from the last dose of investigational product for any subject who terminates early from this study.
Exclusion criteria
* Subjects that have completed Day 84 (Week 12) of study B0151003, and experienced serious event(s) related to the investigational product, an unstable medical condition, or any other reason, in the opinion of the investigator, would preclude entry or inclusion in this study. * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate entry into this study. * Received any prohibited treatment during study B0151003 that, in the opinion of the investigator, compromised the safety or efficacy of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Belgium, Brazil, Canada, Czechia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, New Zealand, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-04236921 All participants entering this study were given a 50 mg SC dose of PF-04236921 at baseline and then every 8 weeks through Week 40. The participants were on active treatment through Week 48. A one-time dose escalation to 100 mg was allowed, if participants experienced a clinical deterioration or unacceptably low level of response to study drug. Dose escalation was not allowed before Week 8. | 191 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 16 |
| Overall Study | Lack of Efficacy | 17 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 3 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 41 |
Baseline characteristics
| Characteristic | PF-04236921 |
|---|---|
| Age, Continuous | 40.1 years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male FEMALE | 108 Participants |
| Sex: Female, Male MALE | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 150 / 191 |
| serious Total, serious adverse events | 79 / 191 |
Outcome results
Primary
Number of Participants With On-Treatment Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
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.
Time frame: Baseline up to Week 48
Population: The safety analysis set was defined as all participants who received at least one dose of PF-04236921during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04236921 | Number of Participants With On-Treatment Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Participants with AEs | 171 participants |
| PF-04236921 | Number of Participants With On-Treatment Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Participants with SAEs | 58 participants |
| PF-04236921 | Number of Participants With On-Treatment Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | Participants discontinued due to AEs | 54 participants |
Primary
Percentage of Participants Developing Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs)
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.
Time frame: At Baseline and Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72 and 76.
Population: The safety analysis set was defined as all participants who received at least one dose of PF-04236921during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04236921 | Percentage of Participants Developing Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) | ADA positive | 0.52 percentage of participants |
| PF-04236921 | Percentage of Participants Developing Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) | NAbs positive | 0.52 percentage of participants |