Rheumatoid Arthritis Clinical Trial
Official title:
A Phase II, Randomized, Parallel-group, Open-label, Multicenter Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate
This was a Phase II, randomized, open-label, multicenter study designed to evaluate the immune response to vaccines after administration of 1000 mg of rituximab in subjects with active rheumatoid arthritis (RA) who were receiving background methotrexate (MTX).
Patients were randomized to 2 groups in this study: Group A (active group) and Group B
(control group). Patients with active rheumatic arthritis treated with rituximab in
combination with methotrexate (Group A) were compared with patients treated with
methotrexate alone (Group B).
Group A
Group A patients received rituximab 1000 mg intravenously (IV) on Days 3 and 17 of the 36
week treatment period.
At Day 1 and at Week 24, patients received an intradermal injection of 0.1 mL of C. albicans
on the volar surface of the forearm. Forty-eight to 72 hours after each injection, patients
were evaluated for a delayed-type hypersensitivity response by measuring the diameter of
induration (palpable raised, hardened area of the forearm skin).
At Week 24, patients received a tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL)
intramuscular (IM) injection in the deltoid muscle. Serum levels of tetanus toxoid titers
were obtained at Day 3 immediately prior to the first administration of rituximab, and
immediately prior to and 4 weeks after administration of the tetanus toxoid adsorbed
vaccine.
At Week 28, patients received an IM injection of the 23-valent pneumococcal polysaccharide
vaccine (0.5 mL) in the deltoid muscle. Serum levels for antibodies to 12 pneumococcal
serotypes were measured at Day 3 immediately prior to the first administration of rituximab,
and immediately prior to and 4 weeks after administration of the pneumococcal vaccine.
At Weeks 32 and 33, patients received subcutaneous (SC) keyhole limpet hemocyanin 1 mg.
Serum anti-keyhole limpet hemocyanin antibody levels were measured at Day 3 immediately
prior to the first administration of rituximab, and immediately prior to and 4 weeks after
the first administration of keyhole limpet hemocyanin.
Samples were obtained for the determination of serum rituximab concentration
(pharmacokinetics), peripheral blood CD19 counts (pharmacodynamics), and the presence of
human anti−chimeric antibodies from all patients in Group A.
Group A patients completed the treatment period at Week 36 and, if qualified, had the option
of entering the optional extension re-treatment period. Patients who did not qualify for or
who did not choose to receive the optional extension re-treatment entered the approximately
1-year safety follow-up period. After the safety follow-up period, patients who remained
peripherally CD19-positive B-cell depleted entered the B-cell follow-up period where they
were followed every 12 weeks until their peripheral CD19-positive B cells returned to
baseline values or the lower limit of normal, whichever was lower.
Group B
Because the immune response to vaccines was not likely to be influenced by the knowledge of
treatment assignment or the time-of-year administration, vaccinations of Group B patients
were administered sooner than in the Group A 36 week treatment period.
At Day 1 and at Week 12, patients received an intradermal injection of 0.1 mL of C. albicans
on the volar surface of the forearm. Forty-eight to 72 hours after each injection, patients
were evaluated for a delayed-type hypersensitivity response by measuring the diameter of
induration (palpable raised, hardened area of the forearm skin).
On Day 1, patients received a tetanus toxoid adsorbed booster vaccine (1 mg in 0.5 mL) IM
injection in the deltoid muscle. Serum levels of tetanus toxoid titers were obtained
immediately prior to and 4 weeks after administration of the tetanus toxoid adsorbed
vaccine.
At Week 4, patients received an IM injection of the 23-valent pneumococcal polysaccharide
vaccine (0.5 mL) in the deltoid muscle. Serum levels for antibodies to 12 pneumococcal
serotypes were measured at Day 1, and immediately prior to and 4 weeks after administration
of the pneumococcal vaccine.
At Weeks 8 and 9, patients received SC keyhole limpet hemocyanin 1 mg. Serum anti-keyhole
limpet hemocyanin antibody levels were measured at Day 1, and immediately prior to and 4
weeks after the first administration of keyhole limpet hemocyanin.
Upon completion of the Week 12 visit, Group B patients with active rheumatic arthritis,
defined as a swollen joint count (SJC) ≥ 4 (66 joint count) and a tender joint count (TJC) ≥
6 (68 joint count) were eligible for treatment with 2 infusions of rituximab 1000 mg IV, 14
days apart. Patients received the first infusion of rituximab within 2 weeks after
completing the Week 12 visit and after the second C. albicans skin test had been read.
Patients received methylprednisolone 100 mg IV before each infusion of rituximab.
Group B patients who received treatment with rituximab completed the treatment period
through Week 36 and, if qualified, had the option of entering the optional extension
re-treatment period. Patients who did not qualify for or who did not choose to receive the
optional extension re-treatment entered the approximately 1-year safety follow-up period.
After the safety follow-up period, patients who remained peripherally CD19-positive B-cell
depleted entered the B-cell follow-up period where they were followed every 12 weeks until
their peripheral CD19-positive B cells returned to baseline values or the lower limit of
normal, whichever was lower.
Group B patients who did not qualify for and/or did not choose treatment with rituximab
completed the study at the end of the primary study period (Week 12).
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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