Clinical trial NCT00655824: Long-term Efficacy and Safety of Repeated Ofatumumab Treatment Courses in RA Patients Who Previously Received Ofatumumab or Placebo in Trial Hx-CD20-403
Official title: An Open-label, International, Multi-center, Phase II, Extension Trial Investigating Long-term Efficacy and Safety of Repeated Treatment Courses of Ofatumumab, a Fully Human Monoclonal Anti-CD20 Antibody, in Adult Patients With Active Rheumatoid Arthritis Who Previously Received Ofatumumab or Placebo
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Arthritis, Rheumatoid
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-04-10
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A 3-year open-label trial for patients who previously participated in Trial Hx-CD20-403 and who fulfill the eligibility criteria for this trial (GEN413) . Th e primary purpose of the trial is to evaluate the long-term effectiveness of repeated courses ( a maximum of 9 treatment courses) of ofatumumab in RA patients who previously received ofatumumab or placebo in Trial Hx-CD20-403.

Detailed description: All patients who fulfill the eligibility criteria for this trial , will initiate at least one treatment course of ofatumumab, and depending of subsequent worsening in disease activity will be eligible to received further treatment through the 156 week treatment period: a maximum of a further 8 treatment courses will be given at individualized time intervals . The interval between each treatment course will be at least 16 weeks with the last treatment course given no later than week 130 after baseline (Visit 2A).

After each treatment course the patients will attend their next trial visit 8 weeks after Infusion 1, followed by trial visits every 4 weeks up to Week 24, and subsequently every 8 weeks until the next treatment course.

After completing the Treatment Period or after withdrawing from the Treatment Period prematurely patients will be followed every 12 weeks (Follow-up Period) until CD19+ cells \&/or IgG levels have returned to baseline or normal levels.

Eligibility criteria: Inclusion Criteria:

* Previously received ofatumumab or placebo in Trial Hx-CD20-403.
* Patients on methotrexate therapy (7.5 - 25 mg/week, p.o., i.m., and/or s.c.).
* Oral corticosteroids therapy (≤ 10 mg/day prednisolone or equivalent).
* Active disease at the time of screening as defined by:

  * 3 swollen joints (of 28 joints assessed) and ≥ 3 tender joints (of 28 joints assessed), DAS28≥3.2 (based on ESR)

Exclusion Criteria:

* Use of DMARDs other than methotrexate or exposure to other cell depleting therapy, including investigational compounds \< 6 months prior to Visit 2 A.
* Patients who have received treatment with any non-marketed drug substance within 4 weeks prior to Visit 1 (screening).
* Breast feeding women or women with a positive pregnancy test at Visit 1 (screening).
* Received anti-cancer therapy, corticosteroids (intra-articular, i.m., or i.v.), or live/attenuated vaccinations, or exposure to cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents \< 5 years prior to screening.
* Past or current malignancy, except for Cervical carcinoma Stage 1B or less, Non-invasive basal cell and squamous cell skin carcinoma, Malignant melanoma with a complete response of a duration of \> 10 years, or other cancer diagnoses with a complete response of a duration of \> 5 years.
* Chronic or ongoing active infectious disease requiring systemic treatment.
* Clinically significant cardiac disease, or history of significant cerebrovascular disease.

Significant concurrent, uncontrolled medical conditions, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease

* Known or suspected HIV positive, positive serology for hepatitis B (HB), positive test for Hepatitis C, or positive plasma or white cell JC virus (JCV) PCR (either compartment).
* A circulating IgG level \<lower limit of normal.
* Known hypersensitivity to components of the investigational medicinal product.
* Patients known or suspected of not being able to comply with a study protocol.
* Women of child bearing potential not will to use adequate contraception during study

Primary outcomes:
measure: Time to Treatment Withdrawal
timeFrame: From Baseline up to 144 weeks
Secondary outcomes:
measure: Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour)
timeFrame: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP)
timeFrame: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Time to Re-treatment in Each Treatment Course
timeFrame: Week 16 to Week 104 of each treatment course (up to 125 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Ofatumumab Serum Concentration
timeFrame: Before infusion and at the end of infusion for each Treatment Course (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next TC; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial vi
measure: Number of Participants Achieving American College of Rheumatology (ACR)20
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants Achieving ACR50
timeFrame: Baseline of each TCand 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants Achieving ACR70
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants in the Indicated Categories of the Health Assessment Questionnaire (HAQ)
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With the Indicated Global Disease Assessment Using the VAS
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With the Indicated Pain Score
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With HAHA Response
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Whole Blood Transcriptional Profiles
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Percentage of Cluster of Differentiation (CD)19+, 4+, 3+, and 8+ B-cell Subsets in the Blood
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: CD19+, CD4+, CD3+, and CD8+ Cell Counts, Measured in mm^3
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Ratio of CD 4+/CD8+
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With Rheumatoid Factor (RA Factor) >13 International Units Per Milliliter
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With Anti-cyclic Citrullinated Peptide Antibody (CCP) >6.9 International Units Per Liter
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With B-Lymphocyte Stimulator (BLyS) >2.49 Micrograms Per Liter
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With Interleukin 6 (IL-6) >11.9 Picograms Per Milliliter
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, and Uric Acid
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Assessment of Total Protein (TP) and Albumin
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Assessment of Total Bilirubin (TB) and Creatinine
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Assessment of Alanine Aminotranferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl-transferase (GGT)
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Assessment of Blood Urea Nitrogen (BUN)
timeFrame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
measure: Assessment of Heart Rate (HR)
timeFrame: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
measure: Assessment of Body Temperature (BT)
timeFrame: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
measure: Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK)
timeFrame: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
measure: Number of Participants With Normal and Abnormal Electrocardiogram Readings
timeFrame: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Duncansville
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Glostrup
country: Denmark
facility: GSK Investigational Site
city: Hellerup
country: Denmark
facility: GSK Investigational Site
city: Koebenhavn
country: Denmark
facility: GSK Investigational Site
city: Szombathely
country: Hungary
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Ipswich
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: