| 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 | 20.0 |
| 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 |
|
| 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 |
| The primary objective for this study is to demonstrate pharmacokinetic (PK) similarity of ABP 798 following 2 intravenous (IV) infusions of 1000 mg each, relative to that of 2 IV infusions of 1000 mg each of rituximab (US) and of rituximab (EU). |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are
•to demonstrate PK similarity between rituximab (US) and rituximab (EU) as assessed by AUCinf and by Cmax after second infusion of the first dose
•to assess the clinical efficacy of ABP 798 compared with rituximab
•to assess the safety and immunogenicity of ABP 798 compared with
rituximab. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Men or women ≥ 18 and ≤ 80 years old
2.Subjects must be diagnosed with RA as determined by meeting 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA
3.Duration of RA of at least 6 months
4.Active RA defined as ≥ 6 swollen joints and ≥ 6 tender joints (based on 66/68 joint count excluding distal interphalangeal joints) at screening and baseline and at least one of the following at screening:
•erythrocyte sedimentation rate (ESR) ≥ 28 mm/hr
•serum C-reactive protein (CRP) > 1.0 mg/dL
5.Subjects have had an inadequate response or intolerance to other DMARDs (which must include intolerance or inadequate response to one or more TNF inhibitor therapies).
6.Subjects must be taking methotrexate (MTX) for ≥ 12 consecutive weeks and be on a stable dose of MTX 7.5 to 25 mg/week for ≥ 8 weeks prior to receiving the investigational product (IP), and be willing to remain on a stable dose throughout the study
7.Subject has no known history of active tuberculosis
8.Subject has a negative test for tuberculosis during screening defined as either:
•negative purified protein derivative (PPD) < 5 mm of induration at 48 to 72 hours after test is placed)
OR
•negative Quantiferon test
9.Subjects with a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test
10.Subjects with a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or subjects with a positive or indeterminate Quantiferon test are allowed if they have all of the following:
•no symptoms per tuberculosis worksheet provided by the Sponsor, Amgen
•documented history of treatment with a TB prophylaxis regimen, with at least 4 weeks of prophylaxis therapy completed at the time of screening. If a subject has completed at least 4 weeks of prophylaxis therapy completed at a time of screening. If a subject has completed at least 4 weeks of prophylaxis therapy, and their regimen requires >4 weeks therapy, the subject must be deemed able and willing to complete the entire prophylaxis regimen in accordance with local guidance.
•no known exposure to a case of active tuberculosis after most recent prophylaxis
•no evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product |
|
| E.4 | Principal exclusion criteria |
1.History of prosthetic or native joint infection
2.Active infection or history of infections as follows:
•any active infection for which systemic anti-infectives were used within 4 weeks prior to first dose of IP
•a serious infection, defined as requiring hospitalization or IV anti infectives within 8 weeks prior to the first dose of IP
•recurrent or chronic infections or other active infection that, in the opinion of the Investigator, might cause this study to be detrimental to the subject
3.Known history of human immunodeficiency virus
4.Hepatitis B surface antigen (HbsAg), Hepatitis B core antibody (anti-HBc), or Hepatitis C virus (HCV) antibody positivity at screening (unless documentation of hepatitis B virus immunization), or Hepatitis C virus (HCV) antibody positivity at screening
5.Uncontrolled, clinically significant systemic disease such as diabetes mellitus, cardiovascular disease including severe heart failure (New York Heart Association [NYHA] class IV), or severe uncontrolled cardiac disease, renal disease, or liver disease
6.Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma
7.History of neurologic symptoms suggestive of central nervous system demyelinating disease
8.Laboratory abnormalities at screening, including any of the following:
•hemoglobin < 9 g/dL
•platelet count < 100,000/mm3
•white blood cell count < 3,000 cells/mm3
•aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 2.0 x the upper limit of normal
•creatinine clearance < 50 mL/min (Cockroft-Gault formula)
9.Use of commercially available or investigational biologic therapies for RA as follows:
•anakinra, etanercept within 1 month prior to first dose of IP
•infliximab, abatacept, tocilizumab, golimumab, certolizumab within 3 months prior to first dose of investigational product
•other experimental or commercially available biologic therapies for RA within 3 months or 5 half-lives (whichever is longer) prior to first dose of investigational product
10.Live vaccines within 28 days prior to the first dose of investigational product
11.Previous receipt of rituximab or a biosimilar of rituximab, or ocrelizumab
12.For women: pregnant or breast feeding, or planning to become pregnant while enrolled in the study and for 12 months after the last dose of investigational product
13.Sexually active subjects and their partners who are of childbearing potential (ie, neither surgically sterile nor postmenopausal) and not agreeing to use adequate contraception (eg, true abstinence, sterilization, birth control pills, Depo-Provera injections, or contraceptive implants) while on study and for 12 months after the last dose of investigational product.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary PK endpoints will be AUCinf and Cmax |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary PK endpoints will be AUCinf and Cmax following the second infusion of the first dose. Additional PK endpoints will include AUC from time 0 on day 1 prior to the first infusion of the first dose to day 14 (AUC0 14 day), AUC from time 0 on day 1 prior to the first infusion of the first dose to week 12 (AUC0-12 wk), and Cmax following the first infusion of the first dose.
|
|
| E.5.2 | Secondary end point(s) |
The efficacy endpoint is Disease Activity Score (DAS) 28 CRP change from baseline at week 24. The endpoint will also be assessed at weeks 8, 12, 40, and 48.
In addition, ACR20 (20% improvement in ACR core set measurements), ACR50 (at least 50% improvement compared to baseline) and ACR70 (at least 70% improvement compared to baseline) will also be assessed at weeks 8, 12, 24, 40, and 48. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
The efficacy endpoint is Disease Activity Score (DAS) 28 CRP change from baseline at week 24. The endpoint will also be assessed at weeks 8, 12, 40, and 48.
In addition, ACR20 (20% improvement in ACR core set measurements), ACR50 (at least 50% improvement compared to baseline) and ACR70 (at least 70% improvement compared to baseline) will also be assessed at weeks 8, 12, 24, 40, and 48.
Safety endpoints include the following:
•treatment-emergent AEs and serious adverse events (SAEs)
•clinically significant changes in laboratory values and vital signs
•incidence of antidrug antibodies |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| 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) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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 | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 37 |
| 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 |
| Bulgaria |
| Canada |
| Estonia |
| Germany |
| Hungary |
| Poland |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
