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Trial record 3 of 5 for:    PF-06410293

A Comparative Study Between PF-06410293 and Humira® in Combination With Methotrexate in Participants With Active Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04230213
Recruitment Status : Completed
First Posted : January 18, 2020
Results First Posted : August 22, 2022
Last Update Posted : August 22, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
The study will assess the impact of pharmacokinetics (PK), safety and immunogenicity after switches between PF-06410293 and adalimumab and with continuous dosing with adalimumab in combination with methotrexate in subjects with moderately to severely active rheumatoid arthritis.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: PF-06410293 Drug: adalimumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 455 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A RANDOMIZED COMPARATIVE STUDY ASSESSING THE SWITCHING BETWEEN PF-06410293 AND HUMIRA (REGISTERED) IN COMBINATION WITH METHOTREXATE IN PARTICIPANTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS
Actual Study Start Date : January 13, 2020
Actual Primary Completion Date : June 22, 2021
Actual Study Completion Date : June 22, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: Treatment Arm 1
Subcutaneous (SC) injection given every other week
Drug: PF-06410293
SC injection

Drug: adalimumab
SC injection
Other Name: Humira ®

Active Comparator: Treatment Arm 2
SC injection given every other week
Drug: adalimumab
SC injection
Other Name: Humira ®




Primary Outcome Measures :
  1. Maximum Observed Serum Concentration (Cmax) of Adalimumab [ Time Frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) ]
    Cmax refers to maximum observed serum concentration of drug. The geometric coefficient of variation is expressed in percentage.

  2. Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) of Adalimumab [ Time Frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) ]
    Area under the serum concentration curve from time 0 to end of dosing interval (tau), where dosing interval was once every two weeks. The geometric coefficient of variation is expressed in percentage.


Secondary Outcome Measures :
  1. Time to Reach Cmax (Tmax) of Adalimumab [ Time Frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) ]
    Tmax is the time taken (in hours) to reach the maximum serum drug concentration.

  2. Average Serum Concentration (Cav) of Adalimumab [ Time Frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) ]
    Cav was defined as average serum concentration over the dosing interval. The geometric coefficient of variation is expressed in percentage.

  3. Apparent Clearance (CL/F) of Serum Adalimumab [ Time Frame: Pre-dose, 48, 72, 96, 144, 240 and 336 hours post dose on Day 211 (Week 30) ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf). The geometric coefficient of variation is expressed in percentage.

  4. Pre-dose Serum Concentration During Multiple Dosing (Ctrough) of Adalimumab [ Time Frame: Pre-dose on Day 1, 71,113, 155, 169, 183, 197 and 211 ]
    Ctrough was defined as pre-dose serum concentration during multiple dosing and observed directly from data.

  5. Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment Related TEAEs: TP1 [ Time Frame: Day 1 up to maximum of 10 Weeks ]
    An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs included both serious and all non-serious AEs.

  6. Number of Participants With TEAEs, Serious TEAEs and Treatment Related TEAEs: TP2 and Beyond [ Time Frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. TEAE for TP2 and beyond was defined as any AE that occurred after administering the first dose of study treatment after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs.

  7. Number of Participants With Grade 3 or Higher TEAEs: TP1 [ Time Frame: Day 1 up to maximum of 10 Weeks ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs were graded using the Common Terminology Criteria for Adverse Events where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening consequences; urgent intervention indicated; and grade 5= death related to AE. Number of participants with grade 3 or higher TEAEs were presented.

  8. Number of Participants With Grade 3 or Higher TEAEs: TP2 and Beyond [ Time Frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs were graded using the Common Terminology Criteria for Adverse Events where, grade 1=mild AE; grade 2=moderate AE; grade 3=severe AE; grade 4= life-threatening consequences; urgent intervention indicated; and grade 5= death related to AE. Number of participants with grade 3 or higher TEAEs were presented.

  9. Number of Participants Who Discontinued Treatment and Study Due to TEAEs: TP1 [ Time Frame: Day 1 up to maximum of 10 Weeks ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an TEAE in TP1 indicating that the AE caused the participant to be discontinued from the study.

  10. Number of Participants Who Discontinued Treatment and Study Due to TEAEs: TP2 and Beyond [ Time Frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study.

  11. Number of Participants With TEAEs of Special Interest: TP2 and Beyond [ Time Frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) ]
    AEs of special interest (AESI) included: hypersensitivity events (anaphylactic reaction, hypersensitivity, angioedema, delayed immune responses and injection site reactions [ISRs]); blood and lymphatic system events (white blood cell disorders and anemias nonhemolytic and marrow depression); cardiovascular events (cardiac failure, hypertension and myocardial infarction); demyelinating conditions, gastric/hepatic events (gastrointestinal perforation, ulceration, hemorrhage or obstruction and hepatic disorders); infections and infestations (including TB and other opportunistic infections); malignancies (neoplasms benign, malignant and unspecified [including cysts and polyps]) and lupus like syndrome. TEAE was defined as any AE that occurred after the first dose of study treatment administered after randomization in TP2. Number of participants with any AESI were presented in this outcome measure.

  12. Number of Participants With Potential Immunogenic AEs to Study Treatment: TP2 and Beyond Among Anti-drug Antibody (ADA) Positive Participants During TP1 [ Time Frame: TP2 and Beyond: Week 16, 22, 24, 26, 28, 30, 32 ]
    In this outcome, participants who were antidrug antibody (ADA) positive during TP1 were assessed in TP2 and beyond per visit for their ADA status at the time of start of their potential immunogenic AEs including ISRs, medically evaluated board standard MedDRA query (SMQ) of potential hypersensitivity (anaphylactic reactions, hypersensitivity and angioedema), medically evaluated AEs meeting Sampson criteria, cytokine storm and delayed immune responses (DIR). ADA positive was defined as ADA titer >=1.88.

  13. Number of Participants With Potential Immunogenic AEs to Study Treatment: TP2 and Beyond Among ADA Negative Participants During TP1 [ Time Frame: TP2 and Beyond: Week 16, 22, 24, 26, 28, 30, 32 ]
    In this outcome, participants who were ADA negative during TP1 were assessed in TP2 and beyond per visit for their ADA status at the time of start of their potential immunogenic AEs including ISRs, medically evaluated board SMQ of potential hypersensitivity (anaphylactic reactions, hypersensitivity and angioedema), medically evaluated AEs meeting Sampson criteria, cytokine storm and DIR. ADA negative was defined as ADA titer <1.88.

  14. Number of Participants With TEAEs and Serious TEAEs Related to COVID-19: TP1 [ Time Frame: Day 1 up to maximum of 10 Weeks ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. AEs included both serious and all non-serious AEs. TEAEs and serious TEAEs related to Covid-19 as per investigator's assessment were presented.

  15. Number of Participants With TEAEs and Serious TEAEs Related to COVID-19: TP2 and Beyond [ Time Frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. TEAEs and serious TEAEs related to Covid-19 as per investigator's assessment were presented.

  16. Number of Participants Who Discontinued Treatment and Study Due to TEAEs Related to COVID-19: TP1 [ Time Frame: Day 1 up to maximum of 10 Weeks ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP1 was defined as any AE that occurred after the beginning of study treatment in TP1 and before the first dose of study treatment administration after randomization in TP2. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study. TEAEs were related to Covid-19.

  17. Number of Participants Who Discontinued Treatment and Study Due to TEAEs Related to COVID-19: TP2 and Beyond [ Time Frame: Post randomization up to maximum of 4 weeks after last dose (maximum of 26 weeks) ]
    An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAE for TP2 and beyond was defined as any AE that occurred after the first dose of study treatment administration after randomization in TP2 and up to 4 weeks after last dose. AEs included both serious and all non-serious AEs. Participants who discontinued treatment due to TEAEs were those who had an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. Participants who discontinued from study due to TEAE were those who had an AE record indicating that the AE caused the participant to be discontinued from the study. TEAEs were related to Covid-19.

  18. Number of Participants With Laboratory Abnormalities: TP1 [ Time Frame: Day 1 up to maximum of 10 Weeks ]
    Blood samples were collected for the analysis of following laboratory parameters: hematology parameters (hemoglobin, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular hemoglobin concentration platelet count, leukocytes, lymphocytes, neutrophils, eosinophils, monocytes); clinical chemistry parameters (bilirubin, alanine aminotransferase [ALT], blood urea nitrogen [BUN], creatinine, potassium, bicarbonate); urine parameters: urine protein, urine hemoglobin, nitrite, leukocyte esterase and bacteria. Number of participants with any laboratory abnormalities is presented.

  19. Number of Participants With Laboratory Abnormalities: TP2 and Beyond [ Time Frame: Post randomization up to end of study treatment (maximum of 22 weeks) ]
    Blood samples were collected for the analysis of following laboratory parameters: hematology parameters (hemoglobin, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin, erythrocyte mean corpuscular hemoglobin concentration platelet count, leukocytes, lymphocytes, neutrophils, eosinophils, monocytes); clinical chemistry parameters (bilirubin, ALT, BUN, creatinine, potassium, bicarbonate); urine parameters: urine protein, urine hemoglobin, nitrite, leukocyte esterase and bacteria. Number of participants with any laboratory abnormalities is presented.

  20. Number of Participants With Hematology Results by Maximum Common Toxicity Criteria (CTC) Grade: TP2 and Beyond [ Time Frame: Post randomization up to end of study treatment (maximum of 22 weeks) ]
    Blood samples were collected for the analysis of following hematology parameters: anemia, hemoglobin increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased. Laboratory parameters were graded according to National Cancer Institute-CTC version 4.03 where, Grade 0= within normal limits; Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences and Grade 5: death. Categories with at least 1 non-zero value were reported in this outcome measure.

  21. Number of Participants With Chemistry Results by Maximum CTC Grade: TP2 and Beyond [ Time Frame: Post randomization up to end of study treatment (maximum of 22 weeks) ]
    Blood samples were collected for analysis of clinical chemistry parameters: ALT increased, alkaline phosphatase increased (ALP), aspartate aminotransferase increased (AST), blood bilirubin increased, creatinine increased, hypercalcemia, hyperkalemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hyponatremia. Laboratory parameters were graded according to NCI-CTC version 4.03 where, grade 0= within normal limits; Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences and Grade 5: death. Categories with at least 1 non-zero value were reported.

  22. Number of Participants With Laboratory Results Based on Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH) Analysis: TP2 and Beyond [ Time Frame: Post randomization up to end of study treatment (maximum of 22 weeks) ]
    In this outcome measure, liver function laboratory parameters, which included: normal bilirubin and AST/ALT, Temple's Corollary (AST/ALT [more than or equal to] >=3*upper limit normal [ULN] and normal bilirubin), Gilbert's Syndrome or cholestasis (normal AST/ALT and bilirubin >=2*ULN) and Potential Hy's Law Cases (AST/ALT >=3*ULN and Bilirubin>=2*ULN) according to eDISH criteria, were reported.

  23. Baseline, Absolute Week 32 Values for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Change From Baseline in SBP, DBP at Week 32 (EOT/ ET) [ Time Frame: Baseline and Week 32 (end of treatment [EOT]/early termination [ET]) ]
    SBP and DBP were measured in a supine position using an automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.

  24. Baseline, Absolute Week 32 Values for Pulse Rate and Change From Baseline in Pulse Rate at Week 32 (EOT/ET) [ Time Frame: Baseline and Week 32 (EOT/ET) ]
    Pulse rate was measured in a supine position using an automated device preceded by at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.

  25. Baseline, Absolute Week 32 Values for Temperature and Change From Baseline in Temperature at Week 32 (EOT/ET) [ Time Frame: Baseline and Week 32 (EOT/ET) ]
    Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.

  26. Baseline, Absolute Week 32 Values for Respiratory Rate and Change From Baseline in Respiratory Rate at Week 32 (EOT/ET) [ Time Frame: Baseline and Week 32 (EOT/ET) ]
    Baseline value was defined as the most recent measurement prior to the first dose of study treatment after randomization in TP2.

  27. Number of Participants Who Were Anti-Drug Antibodies (ADA) Positive and Neutralizing Antibodies (NAb) Positive [ Time Frame: Week 10, 16, 22, 24, 26, 28, 32 ]
    Serum samples were analyzed using a validated electrochemoluminescent (ECL) immunoassay for ADA assessment. Samples positive for ADA were further tested for neutralizing activity using a validated cell based NAb assay. ADA positive was defined as ADA titer >=1.88 while NAb positive was defined as NAb titer >=0.70.

  28. Mean ADA Titers [ Time Frame: Week 10, 16, 22, 24, 26, 28, 30, 32 ]
    Serum samples were analyzed using a validated ECL immunoassay for ADA assessment. Endpoint titer was defined as log10 of the reciprocal of the ADA serum dilution at which the sample response was equal to the cut-point of the assay.

  29. Mean NAb Titers [ Time Frame: Week 10, 16, 22, 24, 26, 28, 30, 32 ]
    Serum samples were analyzed using a validated ECL immunoassay for ADA assessment. Endpoint titer was defined as log10 of the reciprocal of the NAb serum dilution at which the sample response was equal to the cut-point of the assay.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of RA based on 2010 ACR/EULAR for RA for at least a 4 month duration.
  • Moderately to severely active RA based on local standard of care.

Exclusion Criteria:

-Evidence of untreated or inadequately treated latent or active TB.


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): NCT04230213


Locations
Show Show 72 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:
Study Protocol  [PDF] May 19, 2020
Statistical Analysis Plan  [PDF] July 13, 2021

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04230213    
Other Study ID Numbers: B5381012
2019-000284-24 ( EudraCT Number )
B5381012 ( Other Identifier: Alias Study Number )
First Posted: January 18, 2020    Key Record Dates
Results First Posted: August 22, 2022
Last Update Posted: August 22, 2022
Last Verified: July 2022
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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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents