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Atacicept in Combination With Rituximab in Subjects With Rheumatoid Arthritis (August III) (August III)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00664521
First received: April 21, 2008
Last updated: November 4, 2016
Last verified: November 2016
  Purpose
The primary objective of this study is to assess the safety and tolerability of combined treatment with atacicept and rituximab in subjects with active rheumatoid arthritis (RA) receiving re-treatment with rituximab.

Condition Intervention Phase
Rheumatoid Arthritis
Biological: Rituximab
Drug: Atacicept
Drug: Placebo matched to atacicept
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo Controlled, Multi-centre, Exploratory, Pilot, Phase II Trial of 150mg Atacicept Given Subcutaneously in Combination With Rituximab in Subjects With Rheumatoid Arthritis.

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 64 ]
    An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

  • Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L) [ Time Frame: Week 64 ]
  • Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at Week 32 [ Time Frame: Baseline, Week 32 ]
    Vital signs assessed included blood pressure (systolic and diastolic), pulse and body temperature. Routine safety lab parameters evaluated included red blood cell (RBC), hemoglobin, hematocrit, platelets, mean cellular hemoglobin (MCH), MCH concentration, MCH volume, white blood cell (WBC), lymphocytes, monocytes, eosinophils, basophils, neutrophils, gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), albumin, alkaline phosphatase (AP), aspartate aminotransferase (AST), bilirubin, calcium, creatinine, glucose, potassium, total protein, sodium, uric acid, and blood urea nitrogen. Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.

  • Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32 [ Time Frame: Baseline, Week 32 ]
    Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.

  • Percent Change From Baseline in Anti-pneumococcus Titer at Week 32 [ Time Frame: Baseline, Week 32 ]
    Percent change from baseline was calculated as ([Week 32 value minus baseline value] multiplied by 100) divided by baseline value.


Secondary Outcome Measures:
  • Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP), ACR50-CRP and ACR70-CRP at Week 32 [ Time Frame: Week 32 ]
    ACR20-CRP response: greater than or equal to (>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). ACR50-CRP and ACR70-CRP response are defined as >=50% and >=70% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) respectively together with >=50% and >=70% improvement in at least 3 of the following respectively: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) CRP.

  • Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32 [ Time Frame: Baseline, Week 32 ]
    DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 score ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.

  • Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells [ Time Frame: Baseline, Week 3, 7, 12, 16, 26 and 32 ]
    Flow cytometric analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of total, mature and memory B cell levels.


Enrollment: 27
Study Start Date: March 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab Plus Atacicept
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by atacicept 150 mg subcutaneously once a week from Week 7 to 32.
Biological: Rituximab
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3.
Drug: Atacicept
Atacicept will be administered at a dose of 150 mg subcutaneously once a week from Week 7 to 32.
Placebo Comparator: Rituximab Plus Placebo
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3, followed by placebo matched to atacicept subcutaneously once a week from Week 7 to 32.
Biological: Rituximab
Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3.
Drug: Placebo matched to atacicept
Placebo matched to atacicept will be administered subcutaneously once a week from Week 7 to 32.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects
  • Greater than and equal to (>=) 18 years of age at the time of Informed Consent
  • Who have rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 12 months
  • Subjects must have active disease defined by DAS28 >3.2
  • Subjects must have received previous treatment with rituximab and must be candidates for re-treatment with rituximab
  • Female subjects of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks before study day 1 (SD1), during the treatment period and for 12 months after the last dose of rituximab, and must have a negative urine pregnancy test at the screening visit and SD1
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Current neurological disease excluding migraine
  • Inflammatory joint disease other than rheumatoid arthritis
  • Any contraindication to rituximab as per national label
  • Use of disease-modifying anti-rheumatic drugs (DMARDs; including methotrexate) for less than 3 months or change in dosing regimen within 28 days before SD1, or methotrexate dose regimen >25 mg/week
  • Participation in any interventional clinical trial within 1 month before SD1 (or within 5 half-lives of the investigated compound before SD1, whichever is longer)
  • Prednisone dose regimen >10 mg/day (or equivalent), or change in steroid dosing regimen within 28 days before SD1
  • Active or latent tuberculosis within the year before screening or major infection requiring hospitalization or intravenous anti-infectives within 28 days before SD1
  • Serum Immunoglobulin G (IgG) below 6 gram per liter (g/L)
  • Known hypersensitivity to atacicept or to any of the components of the formulated atacicpet
  • Known hypersensitivity to rituximab, to any of the components of the formulated rituximab or to murine proteins
  • Breastfeeding or pregnancy
  • Other protocol defined exclusion criteria could apply
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00664521

Locations
France
Research Site
Nice, France
Research Site
Paris, France
Research Site
Strasbourg, France
Netherlands
Research Site
Amsterdam, Netherlands
Sweden
Research Site
Malmö, Sweden
Research Site
Stockholm, Sweden
United Kingdom
Research Site
Newcastle, United Kingdom
Research Site
Norwich, United Kingdom
Sponsors and Collaborators
Merck KGaA
  More Information

Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00664521     History of Changes
Other Study ID Numbers: 28155
Study First Received: April 21, 2008
Results First Received: September 16, 2016
Last Updated: November 4, 2016

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 22, 2017