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Completed

NCT Number: NCT00664521

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

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.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Research Site, Nice, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Rituximab

Biological

Rituximab will be administered as an intravenous infusion at a dose of 1000 mg at Weeks 1 and 3.

Atacicept

Drug

Atacicept will be administered at a dose of 150 mg subcutaneously once a week from Week 7 to 32.

Placebo matched to atacicept

Drug

Placebo matched to atacicept will be administered subcutaneously once a week from Week 7 to 32.

Primary outcomes

  1. 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.

  2. Percentage of Participants With Immunoglobulin G (IgG) Level Less Than 3 Gram Per Liter (g/L)

    Time frame: Week 64

  3. 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.

  4. 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.

  5. 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 outcomes

  1. 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.

  2. 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.

  3. 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.

Sponsors and collaborators

Lead sponsor

Merck KGaA, Darmstadt, Germany

Industry

Registry information

Official study 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.

Acronym: August III

Important dates

Study start
2008
Primary completion
2010
Study completion
2010
First posted
Apr 23, 2008
Registry last updated
Dec 30, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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