anti TNF-IR phase III

• Register: EUCTR
• Last refreshed on: 26 August 2013
• Main ID: EUCTR2006-005330-20-DE
• Date of registration: 09/03/2007
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: anti TNF-IR phase III
• Scientific title: A randomized, double-blind, parallel group, international study to evaluate the safety and efficacy of ocrelizumab compared to placebo in patients with active rheumatoid arthritis who have an inadequate response to at least one anti-TNF-a therapy.
• Date of first enrolment: 18/07/2007
• Target sample size: 800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-005330-20
• 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, France, Germany, Hungary, Italy, Netherlands, Slovenia, Spain, Sweden

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Target population
Patients with active rheumatoid arthritis who have experienced an inadequate response to previous or current treatment with at least one anti-TNF-a-agent, such as etanercept, infliximab or adalimumab because of toxicity or inadequate efficacy.

Inclusion Criteria
Patients must meet the following criteria to be eligible for study entry:
1. Ability and willingness to provide written informed consent and to comply with the requirements of the protocol

2. Age =18 years

3. Have active disease defined as:
a) Diagnosis of RA of at least 3 months duration using the ACR criteria for the classification of RA.
b) Swollen joint count (SJC) =4 (66 joint count) and tender joint count (TJC) = (68 joint count) at screening and baseline.
c) CRP =0.6 mg/dL using a high-sensitivity assay.
d) Positive rheumatoid factor or positive anti-CCP antibody or both.

4. Previous and current treatments:
a) Current treatment for RA on an outpatient basis.
b) Experienced an inadequate response to previous or current treatment with at least one anti-TNF-a-agent, such as
etanercept, infliximab or adalimumab because of toxicity or inadequate efficacy. An adequate trial of therapy (to define inadequate efficacy) is defined as follows:
•Etanercept dose: 25 mg twice weekly or 50 mg once weekly for =3 months
•Infliximab dose: =3 mg/kg for at least 3 infusions
•Adalimumab dose: 40 mg every other week or 20 mg weekly for =3 months
Etanercept therapy should be discontinued at least 4 weeks prior to the baseline visit, while infliximab and
adalimumab therapy should be discontinued at least 8 weeks prior to baseline.
c) Patients must be receiving either
•Leflunomide at a dose of 10-20 mg once daily for at least 12 weeks, with the last 4 weeks, prior to baseline at a stable dose, or
•Methotrexate at a dose of 7.5-25 mg/week (p.o or parenteral) for at least 12 weeks, with the last 4 weeks, prior to baseline at a stable dose,
•Patients receiving both methotrexate and leflunomide must discontinue one of the two prior to baseline.
Under this circumstance methotrexate should be discontinued for at least 4 weeks prior to baseline and leflunomide should be discontinued for 12 weeks or 4 weeks after 11 days of standard cholestyramine or activated charcoal drug removal prior to baseline.
d) If receiving other non-biologic DMARDs, these agents should have been administered for at least 12 weeks, with the last 4 weeks, prior to baseline at a stable dose.
e) If receiving non-anti-TNF-a biologic DMARDs (such as abatacept, anakinra) these agents should be washed out at least four weeks prior to baseline.
f) If receiving current treatment with corticosteroids, the dose must not exceed 10 mg/day prednisolone or equivalent and during the four weeks prior to baseline it must be at a stable dose.
g) If receiving current treatment with NSAIDs, the patient must be on a stable dose for the 4 weeks prior to baseline.
h) Patients receiving methotrexate must be willing to receive oral folic acid or equivalent.

5. Other:
a) For patients of reproductive potential (males and females), a reliable means of contraception must be used for the duration of the study (e.g., hormonal contraceptive, intrauterine device, physical barrier) according to local guidelines.
b) Female patients of childbearing age must have a negative urine pregnancy test.


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
Exclusion criteria:
Exclusion Criteria Related to Rheumatoid Arthritis
1. Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty’s syndrome). Patients with secondary Sjögren’s syndrome or secondary limited cutaneous vasculitis with RA are eligible.
2. Functional Class IV as defined by the ACR Classification of Functional Status in RA
3. History of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome).

Exclusions Related to General Health
4. Any surgical procedure, including bone or joint surgery/synovectomy (including joint fusion or replacement) within 12 weeks prior to or planned within 48 weeks after baseline.
5. Sepsis in a prosthetic joint within the last 48 weeks or indefinitely if the prosthesis concerned remains in situ.
6. Lack of peripheral venous access.
7. Pregnancy or lactation.
8. Known significant cardiac disease (NYHA Class III and IV)
9. Known severe chronic obstructive pulmonary disease
(COPD) (FEV1 < 50% predicted or functional dyspnoea =Grade 3 on the MRC Dyspnoea Scale)
10. Evidence of significant uncontrolled concomitant diseases such as nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the investigator’s opinion, would preclude patient participation.
11. Any neurological (congenital or acquired), psychiatric, vascular or systemic disorder which could affect any of the efficacy assessments, in particular, joint pain and swelling (e.g. Parkinson’s disease, cerebral palsy, diabetic neuropathy, chronic fatigue syndrome, chronic remitting anemia of unknown origin or requiring transfusion).
12. Uncontrolled disease states where flares are commonly treated with oral or parenteral corticosteroids.
13. Primary or secondary immunodeficiency (history of, or currently active), including known history of HIV infection.
14. Known active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with iv anti-infectives within 4 weeks of baseline or oral anti-infectives within 2 weeks prior to baseline.
15. History of deep space/tissue infection (e.g. fasciitis, abscess, osteomyelitis, septic arthritis of a native joint) within 48 weeks of baseline.
16. Evidence of chronic active hepatitis B or C
17. Evidence of active tuberculosis (patients receiving chemoprophylaxis for latent tuberculosis infection are eligible for the study)
18. History of serious recurrent or chronic infections not specified above.
19. History of cancer within the last 10 years, including solid tumors and hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that have been excised and cured).
20. Currently active alcohol or drug abuse or history of alcohol or drug abuse within 24 weeks prior to baseline.

Exclusion Criteria Related to Medications
21. History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of ocrelizumab infusion
22. Treatment with any investigational agent 12 weeks or five half-lives of

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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 15.0 Level: SOC Classification code 10028395 Term: Musculoskeletal and connective tissue disorders System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: ocrelizumab
Product Code: RO 496-4913
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ocrelizumab
Current Sponsor code: RO 496-4913
Other descriptive name: RhuMAb 2H7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To determine the efficacy and safety of ocrelizumab versus
placebo in reducing signs and symptoms of rheumatoid arthritis (RA), when used in
combination with methotrexate (MTX) or leflunomide given either alone or in
combination with other non-biologic Disease Modifying Anti-Rheumatic Drugs (DMARD) in patients with active RA who have an inadequate response to at least
one anti-TNF-a therapy.

Timepoint(s) of evaluation of this end point: 1. 24 weeks
2. 48 weeks.

Secondary Objective: • To assess the efficacy of ocrelizumab to slow or inhibit
structural damage
• To assess the effect of ocrelizumab on physical function
• To investigate the pharmacokinetics and pharmacodynamics
of ocrelizumab

Primary end point(s): Co-Primary Endpoints
1. Proportion of patients with ACR20 responses
2. Proportion of patients with ACR20 responses
ACR= American College of Rheumatology

Secondary ID(s)

2006-005330-20-BE

WA20495

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd.