This trial is designed to determine the effects the investigational medicine, ABP 798 has on the human body , and what effects the investigational medicine after you have been given it, and if this is comparable to what is seen for the licensed medicine, rituximab, in patients with moderate or severe rheumatoid arthritis (RA). This study will assess if the investigational medicine is safe and effective in treating moderate or severe RA compared to the licensed medicine.

• Register: EUCTR
• Last refreshed on: 4 December 2018
• Main ID: EUCTR2013-005543-90-BG
• Date of registration: 22/10/2014
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: This trial is designed to determine the effects the investigational medicine, ABP 798 has on the human body , and what effects the investigational medicine after you have been given it, and if this is comparable to what is seen for the licensed medicine, rituximab, in patients with moderate or severe rheumatoid arthritis (RA). This study will assess if the investigational medicine is safe and effective in treating moderate or severe RA compared to the licensed medicine.
• Scientific title: A Randomized, Double-Blind Study to Compare Pharmacokinetics and Pharmacodynamics, Efficacy and Safety of ABP 798 With Rituximab in Subjects With Moderate to Severe Rheumatoid Arthritis - Not applicable
• Date of first enrolment: 06/01/2015
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005543-90
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Canada, Estonia, Germany, Hungary, Poland, United States

Contacts

• Name: IHQ Medical Info-Clinical Trials
• Affiliation: Amgen (Europe) GmbH

• Name: IHQ Medical Info-Clinical Trials
• Affiliation: Amgen (Europe) GmbH

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: ABP 798
Product Code: ABP 798
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rituximab
CAS Number: 1446410-99-6
Current Sponsor code: ABP 798
Other descriptive name: ABP 798 - Biosimilar to rituximab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Rituxan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Other descriptive name: Rituxan
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: MabThera
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Other descriptive name: MabThera
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: 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).

Primary end point(s): The primary PK endpoints will be AUCinf and Cmax

Secondary Objective: 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.

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.

Secondary Outcome(s)

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.

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

Secondary ID(s)

2013-005543-90-HU

20130108

Source(s) of Monetary Support

Amgen Inc