A Phase IIIb, open-label, run-in and double-blind, placebo-controlled, randomized study to evaluate the safety and efficacy of certolizumab pegol administered concomitantly with stable-dose methotrexate in patients with active rheumatoid arthritis

• Register: EUCTR
• Last refreshed on: 4 April 2022
• Main ID: EUCTR2007-005288-86-FR
• Date of registration: 30/07/2008
• Prospective Registration: Yes
• Primary sponsor: UCB Pharma S.A.
• Public title: A Phase IIIb, open-label, run-in and double-blind, placebo-controlled, randomized study to evaluate the safety and efficacy of certolizumab pegol administered concomitantly with stable-dose methotrexate in patients with active rheumatoid arthritis
• Scientific title: A Phase IIIb, open-label, run-in and double-blind, placebo-controlled, randomized study to evaluate the safety and efficacy of certolizumab pegol administered concomitantly with stable-dose methotrexate in patients with active rheumatoid arthritis
• Date of first enrolment: 18/03/2009
• Target sample size: 335
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005288-86
• 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: yes Other trial design description: the run-in period is open-label If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients must be at least 18 years old at the screening visit.
2. Patients must be able to understand the information provided to them and to give written Informed Consent.
3. Female patients must be either postmenopausal for at least one year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (either oral/parenteral/implantable hormonal contraceptives, intrauterine device or barrier and spermicide). Abstinence only is not an acceptable method. Patients must agree to use adequate contraception during the study and for 12 weeks after the last dose of certolizumab pegol. Male patients must agree to ensure they or their female partner(s) uses adequate contraception during the study and for 12 weeks after the patient receives their last dose of certolizumab pegol.
4. Patients must have a diagnosis of adult–onset RA of at least six months duration but not longer than fifteen years as defined by the 1987 American College of Rheumatology classification criteria.
5. Patients must be rheumatoid factor positive and/or anti-CCP positive.
6. Patients must have active RA disease as defined by:
• =6 tender joints (28 joint count) at Screening and Baseline; and
• =4 swollen joints (28 joint count) at Screening and Baseline; and
• =10 mg/L (>1 mg/dL) CRP AND/OR > 28mm/hour ESR (Westergren)
7. Patients must have received treatment with MTX (10-25 mg/week, with or without folic acid) for at least three months prior to the Baseline visit. The dose of MTX and route of administration must have been stable for at least 2 months prior to the Baseline visit. The minimum stable dose of MTX allowed is 10 mg weekly.
8. Patients must be able and willing to comply with the requirements of the study protocol.

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:
1. Patients must not have a diagnosis of any other inflammatory arthritis
2. Patients must not have a secondary, non–inflammatory type of arthritis 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.
3. Patients must not have a history of an infected joint prosthesis at any time with that prosthesis still in situ.
4. Patients must be free of prohibited medication as detailed in the protocol.
5. Patients must not have received any experimental non–biological therapy, within or outside of a clinical trial in the three months prior to Baseline visit.
6. Patients must not have received any experimental biological agent in the past three months or within 5 half-lives prior to Baseline (whichever is longer).
7. Patients must not have received any biological therapy for RA within three months prior to Baseline visit, except for etanercept or anakinra for which a one month washout prior to Baseline visit is acceptable.
8. Patients must not have received previous treatment with a biological therapy for RA that resulted in a severe hypersensitivity reaction or an anaphylactic reaction.
9. Patients who failed to respond to previous treatment with an anti–TNF drug (i.e., primary failures) are excluded. Patients who initially responded to a previous treatment with an anti-TNF drug but who later discontinued that drug due to loss of efficacy or financial or other reasons (other than severe hypersensitivity reaction or an anaphylactic reaction) may be included.
10. Female patients who are breast-feeding, pregnant, or plan to become pregnant during the trial or within three months following last dose of study drug.
11. 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.
12. Patients with active TB (or history of active TB), positive chest X–ray for TB, or positive PPD skin test (defined as induration of = 5mm) or patients having close contact with an individual with active TB. Patients having PPD skin test = 5mm can enter the study, provided that active TB is excluded and provided that they are adequately treated for latent tuberculosis and provided that treatment is initiated at least 1 month prior to first administration of certolizumab pegol.
13. Patients at a high risk of infection (e.g., the presence of leg ulcers or an indwelling urinary catheter, persistent or recurrent chest infections, or patients who are permanently bedridden or wheelchair bound).
14. Patients with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease.
15. Patients with concurrent acute or chronic viral hepatitis B or C.
16. Patients with known human immunodeficiency virus (HIV) infection.
17. Patients receiving any vaccination (live or attenuated) within eight weeks prior to Baseline (e.g., inactivated influenza and pneumococcal vaccines are allowed but nasal influenza vaccination is not permitted).
18. 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).
19. Patients with a history of blood dyscrasias.
20. Patients with a current or recent history of severe

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

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: certolizumab pegol
Product Code: CDP870
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Certolizumab pegol
CAS Number: 428863-50-7
Current Sponsor code: CDP870
Other descriptive name: Anti-TNF humanized antibody Fab' fragment - PEG conjugate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: All patients, to assess at week 16:
- clinical response rate
- reduction of disease activity
- achievement of clinical remission
- improvement in physical function
To evaluate tolerability and safety of CZP therapy in patients with active RA on a stable dose of concomitant MTX therapy

In patients randomized at Week 18, to assess at week 34:
- clinical response rate
- reduction of disease activity
- achievement of clinical remission
- improvement in physical function
- reduction in fatigue
- improvement in
- patient’s Health-Related Quality of Life
- arthritis pain
- disease activity
To assess the time to loss of ACR20 response (at 2 consecutive visits) after Week 18

Exploratory Objectives:
To explore:
- pharmacokinetic profile and immunogenicity of the different dose regimens.
- impact of CZP therapy on patient’s height, used as a surrogate endpoint for bone strength.
- impact of CZP therapy on the patient’s lipid profile

Main Objective: To assess the clinical efficacy of two dose regimens of certolizumab pegol (200 mg administered Q2W and 400 mg administered Q4W) in combination with MTX as compared to MTX alone for maintenance of clinical response over an additional 16 weeks in patients who have responded (i.e. achieved ACR20) to the initial 18-weeks of treatment (certolizumab pegol 400mg at Weeks 0, 2 and 4 followed by 200 mg certolizumab pegol and placebo at Weeks 6, 8, 10, 12, 14 and 16 plus MTX).

Primary end point(s): The primary efficacy variable is the ACR20 responder rate at Week 34 (V19) in the patients randomized at Week 18.

Secondary Efficacy Variables
All patients, at week 16:
- ACR20, ACR50 and ACR70 responder rate
- Change from Baseline in DAS28, SDAI and CDAI scores
- DAS28 remission (<2.6) rate, SDAI remission (=3.3) rate and CDAI remission (=2.8) rate
- Change from Baseline in HAQ–DI

In the patients randomized at Week 18,
at week 34:
- ACR50 and ACR70 responder rate
- Change from Baseline in DAS 28, SDAI and CDAI scores
- DAS28 remission (<2.6) rate, SDAI remission (=3.3) rate and CDAI remission (=2.8) rate
- Change from Baseline in HAQ–DI
- Change from Baseline in the Fatigue Assessment Scale
- Change from Baseline in SF-36 domains as well as Mental and Physical Component Summary score (MCS and PCS)
- Change from Baseline in the Patient’s Assessment of Arthritis Pain-VAS
- Change from Baseline in the Patient’s Global Assessment of Disease Activity-VAS
The time to loss of ACR20 response (at 2 consecutive visits) after week 18

Pharmacokinetic and Pharmacodynamic Variables:
Plasma samples for the measurement of certolizumab pegol concentrations and anti- certolizumab pegol antibodies will be collected at Baseline and Weeks 16, 28 and 34.

Safety variables to be assessed are adverse events, vital signs, physical examination, including symptoms of active tuberculosis, and measurements of laboratory parameters.

Clinical laboratory values (hematology, biochemistry and urinalysis) will be collected and assessed.

Secondary ID(s)

C87077

Ethics review

Status: Approved
Approval date: 15/10/2008
Contact:

Results

• Results available: Yes
• Date Posted: 25/12/2016
• Date Completed: 01/03/2011
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-005288-86/results