None listed
Conditions
Interventions
Switching arm (PF-06410293 and Adalilumab) Type of group
Name of the intervention: PF-06410293
Pharmaceutical form: Sterile solution
Dosage and frequency: 40mg/ 0.8 mL or 40mg/ 0.4 mL every 2 weeks
Duration of treatment: 32 weeks
Route of administration: subcutaneous
Group name:Non- switching arm, Adalimumab Type of group
Name of the intervention: Adalilumab (Humira)
Pharmaceutical form: Sterile solution
Dosage and frequency: 40mg/ 0.4 mL cada 2 semanas
Duration of treatment: 32 semanas
Route of administration: subcutanea
Sponsors
Pfizer Inc.,
Eligibility
Inclusion criteria
Inclusion criteria: Age and Sex: 1. Male or female participants between the ages of 18 (or the minimum country-specific age of consent if >18) and 70 years, inclusive, at Visit 1 (Screen 1). Type of Participant and Disease Characteristics: 2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures. 3. Diagnosis of rheumatoid arthritis (RA) based on 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA for at least a 4 month duration. 4. Moderately to severely active RA disease based on local standard of care. 5. Must have received oral, subcutaneous (SC), or intramuscular (IM) methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks prior to first dose of investigational product on Day 1 of TP1. The stable dose must be 10 to 25 mg per week, with the exception of 6 to 25 mg per week where 6 mg per week is a recommended initial dose by local guidance or standard of care. 6. Stable dose of oral folic acid (at least 1 mg/day on ≥5 days per week) or oral folinic acid (≥5 mg once per week) supplementation for at least 21 days prior to the first dose of investigational product on Day 1 of TP1. In countries which do not have approved folic acid 1 mg or folinic acid 5 mg presentations, a regimen of folic acid of ≥5 mg weekly is acceptable. 7. Prior lymphocyte depleting therapies (eg, rituximab, Campath) must have normal lymphocyte counts at the time of screening and no remaining depletion is documented. Weight: 8. Body mass index (BMI) of 18 to 45 kg/m2 and a total body weight of ≥40 kg (88 pounds) to ≤130 kg (287 pounds). Informed Consent: 9. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.
Exclusion criteria
Exclusion criteria: Medical Conditions: 1. Evidence or history of nervous system demyelinating diseases (including multiple sclerosis, optic neuritis, Guillain-Barre syndrome). 2. History of seizure disorder requiring treatment in the previous 5 years prior to Screening. 3. History of significant infection defined by: a. History of recurrent (more than one episode) limited herpes simplex which requires current chronic antiviral therapy, or disseminated (a single episode) herpes simplex. b. History of disseminated or recurrent infection with Epstein Barr virus (EBV), human papilloma virus (HPV), or varicella zoster. A single, limited episode in the past is not exclusionary. c. Any infection requiring hospitalization or parenteral antimicrobial therapy judged clinically significant by the investigator within 6 months prior to first dose of investigational product. d. History of an infected joint prosthesis at any time,with the prosthesis still in situ. 4. Known or Screen test positive for human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C (HCV) virus. 5. Evidence of current or recent history of uncontrolled, clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, hepatic, infectious, psychiatric, neurologic, allergic, or cardiovascular disease including evidence or history of moderate or severe heart failure (NYHA Class III/IV) or Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities which may affect participant safety, and participants who are contraindicated for treatment with adalimumab in accordance with the approved local label. 6. History of any lymphoproliferative disorder (eg, EBV related lymphoproliferative disorder, lymphoma, or leukemia). Evidence or history of a malignancy within the past 5 years (with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ with no evidence of recurrence). 7. History of recurrent inflammatory joint disease other than RA (eg, post infectious arthritis, gout, etc.) or history of any other autoimmune rheumatic diseases (eg, vasculopathies, spondyloarthropathies, etc.) other than Sjogren’s syndrome. 8. Significant trauma or surgical procedure within 4 weeks prior to first dose of investigational product. 9. History of severe allergic or hypersensitivity or anaphylactic reaction to a biologic drug or to active or inactive components of the investigational product. 10. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product (IP) administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Prior/Concomitant Therapy: 11. Prior/Current treatment with adalimumab. 12. Prior biologic therapy other than adalimumab that has not had a washout period of at least 12 weeks or 5 half-lives prior to the first dose of investigational product on Day 1 of TP1, whichever is longer. 13. Prior lymphocyte depleting therapies (eg, rituximab, Campath) does not have normal lymphocyte counts at the time of screening and remaining depletion is documented. 14. K
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Interchangeability will be established statistically if the 90% confidence interval (CI) for the geometric mean ratio (GMR) is within 80.00% to 125.00% for both Cmax and AUCτ. ANOVA will be used for comparing switching arm vs non-switching arm for Cmax and AUCτ. Measure:Maximum observed concentration (Cmax) and Area under the concentration - time curve over the dosing interval (AUCτ) Timepoints:Between Week 30 and Week 32 | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Will be summarized descriptively for switching arm and nonswitching arm using PK population Measure:Time at which Cmax occurs(Tmax), Average concentration (Cav), and Apparent clearance (CL/F) Timepoints:Between Week 30 and Week 32 ; Outcome name:Safety analyses for treatment period 1 (TP1) will be performed using the Safety-TP1 population for the Humira arm. Safety analyses for treatment period 2 (TP2) through treatment period 4 (TP4) will be performed using Safety-Randomized populations by switching arm and non-switching arm. Measure:Safety endpoints (Including adverse events (AEs), laboratory test, vital signs and physical examination) of switching arm and non-switching arm. Timepoints:From Baseline (Week0/Day1 to week 32/End of Treatment (EOT)/ Early Termination(ET). ; Outcome name:For the ADA and NAb data, the percentage of participants with positive ADA and NAb will be calculated and summarized for the Safety-Randomized population by each visit for TP1 through TP4. Measure:Antidrug antibodies (ADA) and Neutralizing antibodies (Nab) endpoints including percent of participants with ADA/NAb and ADA/NAb titers over time Timepoints:From Baseline (Week0/Day1 to week 32/End of Treatment (EOT)/ Early Termination(ET). | — |
Countries
Argentina, Bosnial and Herzegovina, Bulgaria, Czech Republic, Lithuania, Mexico, Peru, Poland, Russian Federation, Serbia, South Africa, Ukraine, United States
Contacts
Public ContactCARLA OLIVERA
PFIZER S.A.
Outcome results
None listed