E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003268 |
E.1.2 | Term | Arthritis rheumatoid |
E.1.2 | System Organ Class | 100000004859 |
|
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 provide continued treatment access to subjects with active rheumatoid arthritis who have participated for at least 16 weeks in other studies in the rituximab-Pfizer program.
To evaluate the overall safety, tolerability and immunogenicity of rituximab-Pfizer occurring after transition from a licensed rituximab product to rituximab-Pfizer.
To continue follow-up of biomarker and efficacy endpoints of interest in previous studies in the rituximab-Pfizer program contributing to this protocol. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
2. Participated for a minimum of 16 weeks after the initiation of the last course of treatment in a previous rheumatoid arthritis study in the rituximab-Pfizer program within the past 2 months.
3. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 12 months after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
4. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial. |
|
E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study:
1. Subjects who are investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the study.
2. Pregnant females; breastfeeding females; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for 12 months after last dose of investigational product. Women of childbearing potential must test negative for pregnancy prior to enrollment in this study.
3. Initiated treatment with investigational agents or other biologics (including Rituxan and MabThera) since participating in a previous rheumatoid arthritis study in the rituximab-Pfizer program.
4. Requirement for treatment during study with prohibited concomitant medications listed in Appendix 1.
5. Severe reaction to licensed rituximab product or rituximab-Pfizer (eg, anaphylaxis).
6. Serious adverse event that was assessed as related to study drug in the prior study.
7. Absolute neutrophil count (ANC) ≤ 1500 cells/mm^3. ANC may be repeated one time to establish eligibility.
8. IgG levels <300 mg/dL. IgG may be repeated one time to establish eligibility.
9. 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 for entry into this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Type, incidence, severity, timing, seriousness and relatedness of adverse events and
laboratory abnormalities including those occurring after transition from a licensed
rituximab product to rituximab-Pfizer.
• Incidence of anti-drug antibodies (ADA), including neutralizing antibodies, and drug concentrations.
• CD19+ B-cell count.
• Serum biomarkers IgG, IgM, RF, anti-CCP and complement.
• Mean change from initial study baseline in DAS28-CRP, EULAR response, LDAS (≤ 3.2), and DAS-CRP remission (<2.6).
• ACR response, calculated from initial study baseline.
• Change from initial study baseline in individual components of ACR response.
• Outcome measure using HAQ-DI. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Documentation of AEs - Each clinic visit, including follow-up.
• ADA and Drug Concentrations - Each course: Days 1, 15 ± 3, 85 ± 7 and 169 ± 7. Follow-up: every 3 months.
• CD19+ B-cell count - Each course: Days 1, 36 ± 7, 85 ± 7 and 169 ± 7 (except no Day 36 in 3rd course) and every 3 months during follow-up.
• Serum IgG, IgM - Screening (Days -28 to -1), Each course: Days 1, 169 ± 7 (except no Day 1 in 1st course).
• RF, anti-CCP and complement - Each course: Days 1 and 169 ± 7.
• HAQ-DI, DAS28-CRP and ACR response – Each course: Days 1, 36 ± 7, 85 ± 7 and 169 ± 7 (except no Day 36 in 3rd course). |
|
E.5.2 | Secondary end point(s) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
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 |
Immunogenicity:
- of treatment with rituximab-Pfizer
- after transitioning from Rituxan or MabThera to rituximab-Pfizer |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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 | 3 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 41 |
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 |
Brazil |
Canada |
Colombia |
France |
Germany |
Israel |
Italy |
Mexico |
Peru |
Poland |
Russian Federation |
South Africa |
Spain |
Taiwan |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |