GP2013 in the Treatment of RA Patients Refractory to or Intolerant of Standard Therapy

• Register: EUCTR
• Last refreshed on: 9 January 2017
• Main ID: EUCTR2010-021184-32-BG
• Date of registration: 14/04/2015
• Prospective Registration: Yes
• Primary sponsor: Hexal AG
• Public title: GP2013 in the Treatment of RA Patients Refractory to or Intolerant of Standard Therapy
• Scientific title: A randomized, double-blind, controlled study to evaluate pharmacokinetics, pharmacodynamics, safety and efficacy of GP2013 and rituximab in patients with rheumatoid arthritis refractory or intolerant to standard DMARDs and one or up to three anti-TNF therapies
• Date of first enrolment: 27/05/2015
• Target sample size: 124
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021184-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Rituxan Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Belgium, Brazil, Bulgaria, Estonia, France, Germany, Hungary, India, Italy, Poland, Romania, Russian Federation, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Tamas Shisha
• Affiliation: HEXAL AG

• Name: Tamas Shisha
• Affiliation: HEXAL AG

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Patients must give written informed consent before any study-related assessment is performed.
2. Patients must be = 18 years of age.
3. Patients must have a diagnosis of Rheumatoid Arthritis, based on the ACR 1987 criteria.
At least 4 of the following 7 criteria must be fulfilled (and criteria a. through d. must have been present for at least 6 weeks) to confirm the diagnosis of RA:
a. joint morning stiffness of at least one hour
b. swelling of joints in at least three joint areas, diagnosed by a doctor, c. swelling of MCP and wrist joints, diagnosed by a doctor
d. bilateral, symmetric swelling of joints in the same joint areas, diagnosed by a doctor
e. rheumatoid nodule
f. rheumatoid factor seropositivity
g. positive findings in hand radiographs.
4. Patients must have had the diagnosis of RA for at least 6 months at Visit 2.
5. Patients must have active RA at baseline (Visit 2):
• = 6 swollen joints (of 66 joints assessed)
• = 6 tender joints (of 68 joints assessed)
• CRP = 10 mg/L
OR ESR = 28 mm/1st hour
Note: If one of the above criteria is not met at Visit 2, the patient is not eligible for randomization at this time point. A re-assessment (i.e., an additional Visit 2) can be done once within 14 days at the discretion of the investigator. A patient can repeat the whole screening phase (be re-screened) only once.
6. Patients must be seropositive for rheumatoid factor (RF) and/or have antibodies to cyclic citrullinated peptide (anti-CCP) at Visit 1.

For additional inclusion criteria, please refer to section 4.1 of the protocol.
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 99
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
Patients eligible for inclusion in this study must not fulfill any of the following criteria:
1. RA patients with functional status class IV classified according to the ACR 1991 revised criteria.
2. Patients with levels of serum IgG, IgM and IgA below LLN at Visit 1 and/or Visit 2.
3. Patients with systemic manifestations of RA, with the exception of Sjögren’s syndrome.
4. Patients taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine).
5. Female patients nursing (lactating / breast-feeding), pregnant or planning of pregnancy within 12 months after the last infusion of study drug, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (cut-off as defined by the central laboratory).
6. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they are using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and intrauterine devices (IUDs)). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) is not acceptable.
7. Patients who have had any therapy with intra-articular injections (e. g. corticoid) required by a flare up to 4 weeks before randomization.

For additional exclusion criteria, please refer to section 4.2 of the protocol.


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

Health Condition(s) or Problem(s) studied

Refractory rheumatoid arthritis
MedDRA version: 18.0 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: NA
Product Code: GP2013
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rituximab
Current Sponsor code: GP2013
Other descriptive name: NA
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 1000-

Trade Name: Rituxan (INN: Rituximab), brand name in the United States
Product Name: Rituxan
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Primary Outcome(s)

Secondary Objective: To evaluate:
• Additional pharmacokinetic (PK) parameters, pharmacodynamic (PD) and efficacy of GP2013 and MabThera®/Rituxan® in subjects with active RA [ Time Frame: 1.5 years ]
• Safety and tolerability of GP2013 and MabThera®/Rituxan® in patients with RA [ Time Frame: 1.5 years ]
For additional secondary objectives please see full protocol

Primary end point(s): The primary PK variable is
• AUC(0-8), i.e. the PK profile will be derived over the entire 1st treatment course including both infusions, of GP2013 and MabThera®/Rituxan® concentrations determined in serum samples collected over
24 weeks.
The primary analysis will be based on the PAS population in part I of the study and on PAS+A population in part II of the study, with the PAS population used as part of the sensitivity analysis

Main Objective: To assess bioequivalence between GP2013 and MabThera®/Rituxan® in combination with MTX in patients with active Rheumatoid Arthritis who have not responded adequately, or have shown intolerance, to DMARDs, including MTX, and one or up to three anti-TNF therapies.

Timepoint(s) of evaluation of this end point: Primary endpoint determined based on serum samples collected over
24 weeks.

Secondary Outcome(s)

Secondary end point(s): PK parameters: In addition to AUC(0-8) and Cmax of the 1st infusion the PK parameters
• AUC(0-14d), AUC(0-12w), AUC(0-24w), Cmax of the 2nd infusion, and tmax (for both infusions), of rituximab (MabThera®/Rituxan®) concentrations determined in serum samples collected over 24 weeks will be assessed.

PD parameter: • Area under the effect-time curve (AUEC(0-t)) from time 0 (before the 1st infusion) up to the
2nd infusion (AUEC(0-14d)) as a percent change from baseline value derived by the linear- trapezoidal rule.
• Percent peripheral B cell levels relative to baseline by visit.
•Number and % of patients with a B cell count below the limit of quantification by Day 1 (after first infusion), 4, 8, and 15 (before second infusion).

Please refer to the clinical study protocol for additional details.

Timepoint(s) of evaluation of this end point: Please refer to the clinical study protocol Section 6: Visit schedule and assessmentsfor additional details and Table 6-1: Assessment schedule

Secondary ID(s)

GPN013A2301

GP13-201

2010-021184-32-DE

NCT01274182

Source(s) of Monetary Support

HEXAL AG