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

NCT00664521 | Completed Phase 2 Results

• 1 other identifier: 28155
• Study Type: interventional
• Target: 27
• Locations: 4 countries
• Sites: 8

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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.

  Baseline up to Week 64

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

  Week 64

• Percent Change From Baseline in Vital Signs and Routine Safety Lab Parameters at 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.

  Baseline, Week 32

• Percent Change From Baseline in Anti-tetanus and Anti-diphteria Immunization Titer at Week 32

  Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.

  Baseline, Week 32

• Percent Change From Baseline in Anti-pneumococcus Titer at Week 32

  Percent change from baseline was calculated as (\[Week 32 value minus baseline value\] multiplied by 100) divided by baseline value.

  Baseline, Week 32

Secondary Outcomes (3)

• 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

  Week 32

• Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) at Week 32

  Baseline, Week 32

• Median Percentage Change From Baseline in Levels of Total, Mature and Memory B Cells

  Baseline, Week 3, 7, 12, 16, 26 and 32

Study Arms (2)

Rituximab Plus Atacicept

EXPERIMENTAL

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; Drug: Atacicept

Rituximab Plus Placebo

PLACEBO COMPARATOR

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; Drug: Placebo matched to atacicept

Interventions

Rituximab BIOLOGICAL

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

Rituximab Plus Atacicept; Rituximab Plus Placebo

Atacicept DRUG

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

Rituximab Plus Atacicept

Placebo matched to atacicept DRUG

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

Rituximab Plus Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (8)

Research Site

Nice, France

Location

Research Site

Paris, France

Location

Research Site

Strasbourg, France

Location

Research Site

Amsterdam, Netherlands

Location

Research Site

Malmo, Sweden

Location

Research Site

Stockholm, Sweden

Location

Research Site

Newcastle, United Kingdom

Location

Research Site

Norwich, United Kingdom

Location

Related Publications (1)

• van Vollenhoven RF, Wax S, Li Y, Tak PP. Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial. Arthritis Rheumatol. 2015 Nov;67(11):2828-36. doi: 10.1002/art.39262.

  PMID: 26137975 RESULT

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab; TACI receptor-IgG Fc fragment fusion protein

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2008
• First Posted: April 23, 2008
• Study Start: March 1, 2008
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: December 30, 2016
• Results First Posted: December 30, 2016

Record last verified: 2016-11

Locations

GB (2); SE (2); FR (3); NL (1)