| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Moderately to severely active Rheumatoid Arthritis |
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| E.1.1.1 | Medical condition in easily understood language |
Rheumatoid Arthritis is broadly referred to as joint inflammation and has different stages of disease progression. This study is for patients with moderate to severe Rheumatoid Arthritis.
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| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10039073 |
| E.1.2 | Term | Rheumatoid arthritis |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate interchangeability of PF-06410293 and Humira by examining adalimumab steady state pharmacokinetics in a switching arm (following 3 switches between Humira and PF-06410293) as compared to a non-switching arm (receiving only Humira). |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate other serum adalimumab PK parameters in the switching arm and the non switching arm.
• To evaluate the overall safety and tolerability of the switching arm and the non-switching arm.
• To evaluate immunogenicity of the switching arm and the non-switching arm.
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|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply:
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). Refer to Appendix 4 for reproductive criteria for male (Section 10.4.1) and female (Section 10.4.2) participants.
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.
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|
| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Evidence or history of nervous system demyelinating diseases (including multiple sclerosis, optic neuritis, Guillain Barré 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 (please see Section 8.2.8 for details on testing).
a. Positive for HIV.
b. Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) without positive hepatitis B surface antibody (HBsAb) results.
c. Positive hepatitis C antibody (HCV Ab) results and positive confirmatory HCV riboneucleic acid (HCV RNA) results.
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. Known requirement for treatment with prohibited concomitant medications during the study.
15. Exposure to any live vaccines within 4 weeks prior to administration of the first dose of investigational product, or lack of willingness to avoid exposure to any live vaccines during the trial and for at least 2 months after the last dose of investigational product.
16. Intra- articular (IA) corticosteroids administered within 4 weeks prior to Screening.
Prior/Concurrent Clinical Study Experience:
17. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or within 5 half lives preceding the first dose of investigational product used in this study (whichever is longer) is not permitted.
Please refer to section 5.2 of the protocol for a full list of exclusion criteria. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Maximum observed concentration (Cmax) and area under the concentration - time curve over the dosing interval (AUCt) obtained during the intensive PK sampling interval. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint data will be supported by the determination of adalimumab drug concentrations for the 2 week PK Profile.
PK samples will be collected throughout visits 1-12.
Please refer to the clinical trial protocol for more information. Table 1 in the protocol (PK Sampling Table) provides the full PK schedule. |
|
| E.5.2 | Secondary end point(s) |
• Other serum adalimumab PK parameters, including time at which Cmax occurs (Tmax), average concentration (Cav), and apparent clearance (CL/F) obtained during the intensive PK sampling interval and predose concentration during multiple dosing (Ctrough) obtained at scheduled PK sample timpoints.
• Safety measures characterized by type, incidence, severity, timing, seriousness and relatedness of treatment emergent adverse events (AEs) and laboratory test abnormalities.
• Percent of participants with antidrug antibodies (ADA), and neutralizing antibodies (NAb) ADA/NAb and ADA/NAb titers over time. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK samples will be collected throughout visits 1-12.
Please refer to the clinical trial protocol for more information. Table 1 in the protocol (PK Sampling Table) provides the full PK schedule. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | Yes |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Bosnia and Herzegovina |
| Bulgaria |
| Czech Republic |
| Lithuania |
| Mexico |
| Peru |
| Poland |
| Russian Federation |
| Serbia |
| South Africa |
| Ukraine |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study is defined when the last participant in the trial completes the date of last scheduled visit or contact as shown in the Schedule of Activities.
LVLS |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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