Primary Objective:To assess the clinical response rate as measured by American College of Rheumatology 20% (ACR20) response rate at Week 12.Secondary Objective:• To assess:- for all patients at Week 12, and every 8 weeks and at the completion/…
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Source
Brief title
Condition
- Other condition
Synonym
Health condition
reumatoïde artritis
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable is the ACR 20% (American College of Rheumatology
20% response criteria) responder rate at Week 12.
Secondary outcome
For all patients at week 12:
- ACR50 and ACR70 responder rate;
- Change from baseline in DAS28(CRP), SDAI and CDAI scores;
- DAS28(CRP) remission (<2.6) rate, SDAI remission (<=3.3) rate and CDAI
remission (<=2.8) rate;
- Change from baseline in individual components of the ACR, including TJC, SJC,
HAQ-DI, CRP, Patient*s assessment of Arthritis Pain-VAS, Patient*s global
assessment of disease activity-VAS and Physician*s global assessment of disease
activity-VAS;
- Time form randomization to sustained ACR20 response at two consecutive visits
or before week 12;
- EULAR response critera.
Every 8 weeks and the completion/withdrawal visit in the group remaining in the
study after week 12:
- ACR20/50/70 responder rate.
- Change from baseline in DAS28(CRP), SDAI and CDAI scores.
- DAS28(CRP) remission (<2.6) rate, SDAI remission (<=3.3) rate and CDAI
remission (<=2.8) rate
- Change from baseline in individual components of the ACR, including TJC, SJC,
HAQ-DI, CRP, Patient*s assessment of Arthritis Pain-VAS, Patient*s global
assessment of disease activity-VAS and Physician*s global assessment of disease
activity-VAS.
Background summary
Rheumatoid Arthritis is a chronic systemic inflammatory disease that is
associated with significant morbidity and mortality. The disease is
characterized by inflammation of the diarthrodial joints that can result in
pain, swelling and joint damage with secondary deformity and progressive
disability and impairment of patient*s health related quality of life. It is
estimated that about 1% of the population worldwide has RA.
RA is a difficult disease to manage: the disease course is often unpredictable
and currently available therapies are associated with varying degrees of
efficacy and can be associated with significant toxicity. Treatment for RA
includes use of non-steroidal anti-inflammatory drugs (NSAIDs), cyclooygenase-2
(COX-2) selective inhibitors, corticosteroids and disease-modifying
antirheumatic drugs (DMARDs).
Given the accumulating data indicating that there is a benefit in using more
aggressive (i.e. DMARD) therapy earlier in the disease course (as well as the
combination of DMARD therapy), there has been a need for more efficacious
and/or better-tolerated therapies. A significant addition to the therapeutic
armamentarium of RA has been the development of a new category of DMARDs
referred to as the biologic response modifiers, particularly tumor necrosis
factor alpha (TNFα) neutralizing therapies.
The pro-inflammatory cytokine Tumor Necrosis Factor α (TNFα) has been shown to
have a central role in RA.
Certolizumab pegol (CZP) is an engineered, humanized, antibody Fab* fragment
produced in E. coli with specificity for human TNFα that is conjugated to
polyethylene glycol (PEG).
Combination therapy with traditional DMARDs plus anti-TNF agents in patient
with an incomplete response to DMARDS has shown to be significantly better in
reduction of disease activity, improvement of physical function, retardation of
radiographic progression and induction of clinical remission compared to
DMARD-monotherapy. Thus, anti-TNF therapy is an important advance in the
therapy of RA.
Certolizumab pegol (CZP) is effective in the treatment of rheumatoid arthritis
(RA), when combines with methotrexate (MTX) or given as monotherapy. However, a
detailed assessment of CZP in combination with a wide range of traditional
DMARDs commonly used to treat patients with RA in clinical practice is lacking.
There is insufficient data with CZP in patients previously treated with
anti-TNF agent(s). There is a need for additional data to document the safety
and efficacy of switching among TNF antagonists in clinical practice, in order
to guide the choice of treatment after failure of an anti-TNF therapy.
Study objective
Primary Objective:
To assess the clinical response rate as measured by American College of
Rheumatology 20% (ACR20) response rate at Week 12.
Secondary Objective:
• To assess:
- for all patients at Week 12, and every 8 weeks and at the
completion/withdrawal visit in the group remaining in the study after Week 12:
- clinical response rate.
- reduction of disease activity.
- achievement of clinical remission.
- additionally, at Week 12:
- improvement in individual components of the ACR criteria
- Time to sustained ACR20 response.
- European League Against Rheumatism (EULAR) response.
- additionally, every 8 weeks and at completion/withdrawal visit :
- change from Baseline in individual components of the ACR criteria.
• Tolerability and safety of CZP therapy over the first 12 weeks of treatment
and over the open-label treatment extension period.
• To evaluate the influence of some characteristics (as per protocol) on ACR20
response rate at Week 12 and adverse events rate with CZP therapy.
Study design
A Phase IIIb, multicenter study with a 12-week double-blind placebo-controlled
randomized period, followed by an open-label extension phase.
Intervention
Patients will receive CZP 400 mg at week 0, 2, and 4 followed by 200 mg every
two weeks or placebo up to and including week 10.
From week 12 all patients will receive treatment with open-label CZP 200 mg
very other week.
During the double-blinded phase the study drug will be administered at the
hospital by appropriate study personnel. Patients of the open-label phase
patients will be trained at the hospital to self administer. Patients who are
able to self administer CZP and having the appropriate storage conditions at
their homes will be given the opportunity to have home based self
administration.
Study burden and risks
The burden exists of the sc injections with study medications for which the
patient has to visit the hospital every other week during the first 12 weeks.
After 12 weeks the patient will be offered to perform self-injection. In this
case, the hospital has only to be visited every 8 weeks.
Benefits:
CZP 400 mg sc every week was efficacious in reducing signs and symptoms of RA
as well as preventing structural damage of the joints. CZP was also shown to
have rapid onset of action in two phase 3 studies.
The benefits of the C87094 protocol are the potential future availability of a
new treatment for RA, with potential efficacy demonstrated across a broader
population of RA patients.
Risks:
CZP is as TNFα antagonist known to be associated with infections requiring
treatment and reactivation of latent tuberculosis. An association has also been
reported with development of leukemia and lymphoma (not known whether causal
relationship or confounder factors). Other adverse events that have been
infrequently reported in patient treated with TNFα antagonist include
congestive heart failure, drug-induced lupus, seizures, demyelinating disorders
and pancytopenia.
There is currently insufficient safety data to determine whether CZP treatment
is also associated with these AEs. The C87094 protocol excludes patients
thought to be at increased risks of such AEs.
Allée de la Recherche 60
B-1070 Brussels
België
Allée de la Recherche 60
B-1070 Brussels
België
Listed location countries
Age
Inclusion criteria
1. Patients must have a diagnosis of adult-onset RA of at least three months duration as defined by the 1987 American College of Rheumatology classification criteria.
2. Patients must have active RA disease as defined by:
• >=5 tender joints (28 joint count) at Screening and Baseline; and
• >=4 swollen joints (28 joint count) at Screening and Baseline; and
• >=10 mg/L CRP and/or >=28mm/hour ESR (Westergren) at screening.
3. Patients must have had an unsatisfactory response or intolerance to at least one traditional DMARD.
Exclusion criteria
1. Patients must not have a diagnosis of any other inflammatory arthritis (e.g., psoriatic arthritis or ankylosing spondylitis).
2. Patients must not have >3 arthroplasties due to RA and/or Steinbrocker IV functional capacity.
3. Patients must not have a secondary, non-inflammatory type of arthritis (e.g. osteoarthritis or fibromyalgia) that in the Investigator*s opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the patient*s primary diagnosis of RA.
4. Patients must not have a history of an infected joint prosthesis at any time with that prosthesis still in situ.
5. Patients must not have received any biological therapy for RA within two months prior to Baseline visit, except for etanercept or anakinra for which a one month washout prior to baseline visit is acceptable.
6. Patients having discontinued or discontinuing biological therapy for their RA must not have had a severe hypersensitivity reaction or an anaphylactic reaction to more than 1 different biologic agent.
7. Patients must not have received treatment with more than 2 anti-TNF agents prior to enrollment in this trial.
8. Patients must not have received treatment with rituximab and/or abatacept.
9. Patients with a history of chronic infection (more than 4 episodes requiring antibiotics/antivirals during the preceding year), recent serious or life-threatening infection within 6 months (including herpes zoster), or any current sign or symptom that may indicate an infection.
10. Patients with active TB (or history of active TB), positive chest X-ray for TB, or positive PPD skin test or patients having close contact with an individual with active TB. Patients having a PPD skin test >= 5 mm can enter the study, provided that active TB is excluded and provided that they are adequately treated for latent TB and provided that treatment is initiated at least 1 month prior to first administration of CZP.
11. Patients at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and patients who are permanently bedridden or wheelchair bound).
12. Patients with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease.
13. Patients with known concurrent acute or chronic viral hepatitis B or C.
14. Patients with known human immunodeficiency virus (HIV) infection.
15. Patients receiving any vaccination (live or attenuated) within eight weeks prior to baseline (e.g., parenteral influenza and pneumococcal vaccines are allowed, but nasal influenza vaccine is not).
16. Concurrent malignancy or a history of malignancy (other than carcinoma of the cervix or basal cell carcinoma successfully treated more than five years prior to screening).
17. Patients with a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease.
18. Patients with class III or IV congestive heart failure according to the New York Heart Association (NYHA) 1964 classification criteria.
19. Patients with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).
20. Patients with a history of an adverse reaction to PEG.
21. Patients must not have a change in dose regiment for NSAIDs/COX-2 inhibitors 7 days prior to baseline, nor a change in dose regiment for oral corticosteroids 14 days prior to baseline. Patients must also not have received IM/IV/IA corticosteroids nor IA hyaluronic acid within 28 days prior to baseline. Patients must also not have received DMARDs within 3 months prior to baseline.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2008-005427-28-NL |
| ClinicalTrials.gov | NCT00717236 |
| CCMO | NL25860.058.08 |