A randomised, double-blind, placebo-controlled, multicentre, Phase II dose-finding study of atacicept given subcutaneously in subjects with rheumatoid arthritis and inadequate response to TNFa antagonist therapy - A Phase II dose-finding study of atacicept in RA

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-004140-23-NL
• Date of registration: 26/04/2007
• Prospective Registration: No
• Primary sponsor: Merck Serono Int.a branch of Laboratoires Serono SA an affiliate of Merck KgaA, Darmstadt, Germany
• Public title: A randomised, double-blind, placebo-controlled, multicentre, Phase II dose-finding study of atacicept given subcutaneously in subjects with rheumatoid arthritis and inadequate response to TNFa antagonist therapy - A Phase II dose-finding study of atacicept in RA
• Scientific title: A randomised, double-blind, placebo-controlled, multicentre, Phase II dose-finding study of atacicept given subcutaneously in subjects with rheumatoid arthritis and inadequate response to TNFa antagonist therapy - A Phase II dose-finding study of atacicept in RA
• Date of first enrolment: 13/12/2006
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004140-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Bulgaria, Finland, Germany, Greece, Italy, Netherlands, Portugal, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
To be eligible for inclusion into this trial, subjects must fulfil all of the following criteria at the time of screening, unless stated otherwise:
1. Rheumatoid arthritis satisfying American College of Rheumatology (ACR) criteria, with a disease history of at least one year.
2. Male or female >or=18 years of age at time of Informed Consent.
3. Active RA as defined by:
- >or= 8 swollen joints (66-joint count),
- >or= 8 tender joints (68-joint count), and
- CRP >or=10 mg/L (central laboratory) and/or ESR > 28 mm/h.
4. Failure of at least one TNFa antagonist therapy (previously or at the time of screening), defined as having persistent disease activity with a minimum of 8 swollen and 8 tender joints despite treatment with etanercept, infliximab or adalimumab at an approved labelled dose for >or= 3 months. Subjects who have discontinued TNFa antagonist therapy due to intolerance without associated lack of efficacy are not considered to satisfy this criterion.
Subjects with previous treatment failure must have documentation of the treatment failure provided by the treating physician, with a similar benchmark of minimally acceptable disease severity.
5. Current use of at least one DMARD at a stable dose, defined by use for at least 3 months before SD 1 with no changes in dosing regimen in the 28 days before Study Day 1 (SD 1, defined as the day of randomisation and first Investigational Product administration).
6. Rheumatoid factor (RF) positivity and/or anti-cyclic citrullinated peptide (anti-CCP) antibody positivity at screening, according to central laboratory criteria.
7. Written informed consent (obtained before any trial-related procedure). Subjects must review and understand the Informed Consent Form, and must fully understand requirements of the trial and be willing to comply with all trial visits and assessments.
8.Women of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for four weeks prior to beginning trial medication, during the trial and three months after the last dose of trial medication. For the purpose of this study, a woman of childbearing potential is defined as any female patient after puberty, unles post-menopausal for at least two years or surgically sterile. Adequate contraception is defined as two barrier methods, or one barrier method with a spermicide, or an intrauterine device or use of the oral female contraceptive (or other hormonal methods).
9. Women of childbearing potential must have a negative urine pregnancy test at the screening visit.


Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
To be eligible for inclusion in this trial, the subjects must not meet any of the following criteria at the time of screening:
1. Any condition, including laboratory findings or findings in the medical history or pre-trial assessments, that in the opinion of the Investigator constitutes a risk or a contraindication for the subject’s participation to the trial or that could interfere with the trial objectives, conduct or evaluation.
2. Treatment with biologics aiming at B cell modulation, such as rituximab or belimumab, within 2 years before SD 1.
3. Treatment with abatacept, anakinra or tocilizumab within 3 month before SD1.
4. Use of etanercept within 28 days before SD 1, or of infliximab or adalimumab within 60 days before SD 1.
5. Participation in any interventional clinical trial within the 3 months before SD 1 (or within 5 half-lives of the investigated compound before SD 1, whichever is longer).
6. Methotrexate dose regimen > 25 mg/week.
7. Prednisone dose regimen > 10 mg/day (or equivalent) or change in steroid dosing regimen within 28 days before SD 1.
8. Change in NSAID dosing regimen within 28 days before SD 1.
9. Any current active infection, including herpes zoster or Epstein-Barr virus.
10. Positive HIV, hepatitis B or hepatitis C serology.
11. History or presence of active or latent tuberculosis as defined by national recommendations.
12. Opportunistic infection in the last 3 months.
13. History of chronic infections requiring repeated antibiotic treatment.
14. Diagnosis or family history of Creutzfeldt-Jakob disease (CJD).
15. History or presence of uncontrolled or New York Heart Association class 3 or 4 congestive heart failure.
16. History of cancer, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia or carcinoma in situ of the skin or cervix.
17. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AP) level > 2.5 x ULN or total bilirubin > 1.5 x ULN.
18. Inadequate renal function, defined by serum creatinine > 1.5 x ULN.
19. Clinically significant abnormality in any haematological test (for example, haemoglobin < 5.5 mmol/L, WBC < 2.5 x 109/L, platelets < 75 x 109/L).
20. Serum IgG below 6 g/L.
21. Clinically significant abnormality on a chest X ray performed within 3 months before SD 1 or on ECG performed at screening.
22. Known hypersensitivity to atacicept or to any of the components of the formulated atacicept.
23. Immunisation with live vaccines or Ig treatment within one month before SD 1 or need for such treatment during the trial period (including follow-up).
24. Planned major surgery (e.g., joint replacement) during the trial period (including follow-up).
25. Pregnancy or breastfeeding (for female subjects).




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: Atacicept
Product Code: Not Applicable
Pharmaceutical Form: Solution for injection
INN or Proposed INN: atacicept
Other descriptive name: TACI-Fc5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): The proportion of subjects achieving an ACR20 response at Week 26.

Main Objective: To evaluate the efficacy of three dose levels of atacicept in the treatment of signs and symptoms of subjects with active rheumatoid arthritis who have had an inadequate response to previous TNFa antagonist therapy.

Secondary Objective: - To evaluate the safety and tolerability profile of atacicept in the treatment of subjects with active RA.
- To evaluate the exposure-response relationship of atacicept with respect to efficacy and safety in subjects with active RA.
- To gain further information on the effect of atacicept on relevant markers of its mechanism of action and of disease activity.
- To further characterise the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of atacicept.
- The following exploratory objectives may also be addressed (pharmacogenetic analyses will be performed after trial completion only if it is believed that they may benefit the further development of atacicept):
- To identify association between gene polymorphisms and drug response, with a focus on BLyS, APRIL, BAFF-R, TACI, BCMA and HLA-DRB1.
- To identify association between gene expression profiles before and after treatment with drug response.

Secondary ID(s)

2006-004140-23-BE

27298