Long-term Efficacy and Safety of Repeated Ofatumumab Treatment Courses in RA Patients Who Previously Received Ofatumumab or Placebo in Trial Hx-CD20-403

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00655824
• Date of registration: 04/04/2008
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Long-term Efficacy and Safety of Repeated Ofatumumab Treatment Courses in RA Patients Who Previously Received Ofatumumab or Placebo in Trial Hx-CD20-403
• Scientific 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
• Date of first enrolment: January 1, 2008
• Target sample size: 124
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00655824
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Denmark, Hungary, Poland, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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
- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Drug: ofatumumab

Primary Outcome(s)

Time to Treatment Withdrawal [Time Frame: From Baseline up to 144 weeks]

Secondary Outcome(s)

Assessment of Alanine Aminotranferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl-transferase (GGT) [Time Frame: 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.]

Assessment of Body Temperature (BT) [Time Frame: 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]

Assessment of Heart Rate (HR) [Time Frame: 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]

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) [Time Frame: 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.]

Number of Participants With Anti-cyclic Citrullinated Peptide Antibody (CCP) >6.9 International Units Per Liter [Time Frame: 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.]

Number of Participants With the Indicated Global Disease Assessment Using the VAS [Time Frame: 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.]

Assessment of Total Protein (TP) and Albumin [Time Frame: 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.]

Number of Participants With Rheumatoid Factor (RA Factor) >13 International Units Per Milliliter [Time Frame: 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.]

Assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, and Uric Acid [Time Frame: 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.]

Number of Participants With HAHA Response [Time Frame: 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.]

Number of Participants Achieving American College of Rheumatology (ACR)20 [Time Frame: 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.]

Number of Participants With Normal and Abnormal Electrocardiogram Readings [Time Frame: 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.]

Number of Participants With Interleukin 6 (IL-6) >11.9 Picograms Per Milliliter [Time Frame: 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.]

Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) [Time Frame: 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.]

Ratio of CD 4+/CD8+ [Time Frame: 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.]

Number of Participants Achieving ACR70 [Time Frame: 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.]

Assessment of Total Bilirubin (TB) and Creatinine [Time Frame: 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.]

Number of Participants With B-Lymphocyte Stimulator (BLyS) >2.49 Micrograms Per Liter [Time Frame: 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.]

Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response [Time Frame: 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.]

Number of Participants With the Indicated Pain Score [Time Frame: 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.]

Number of Participants in the Indicated Categories of the Health Assessment Questionnaire (HAQ) [Time Frame: 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.]

Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) [Time Frame: 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.]

Time to Re-treatment in Each Treatment Course [Time Frame: 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.]

Whole Blood Transcriptional Profiles [Time Frame: 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.]

Assessment of Blood Urea Nitrogen (BUN) [Time Frame: 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.]

Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Time Frame: 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]

CD19+, CD4+, CD3+, and CD8+ Cell Counts, Measured in mm^3 [Time Frame: 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.]

Number of Participants Achieving ACR50 [Time Frame: 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.]

Ofatumumab Serum Concentration [Time Frame: 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]

Percentage of Cluster of Differentiation (CD)19+, 4+, 3+, and 8+ B-cell Subsets in the Blood [Time Frame: 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.]

Secondary ID(s)

GEN413

111752

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/04/2012
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00655824