Clinical Research Details

C87094: A Phase IIIb, multicenter study with a 12-week double-blind, placebo-controlled, randomized period followed by an open-label, extension phase to evaluate the safety and efficacy of certolizumab pegol administered to patients with active rheumatoid arthritis.

To assess the clinical response rate as measured by American College of Rheumatology 20% (ACR20) response rate at Week 12 ;Secondary Objectives • To assess for all patients at Week 12:The clinical response rate as measured by American College of Rheumatology 50% (ACR50) and American College of Rheumatology 70% (ACR70) ;Secondary Objectives • To assess for all patients at Week 12:The reduction of disease activity by DAS28(CRP) [Disease Activity Score – 28 (C-reactive protein)], SDAI [Simplified Disease Activity Index] and CDAI [Clinical Disease Activity Index] (1,2) ;Secondary Objectives • To assess for all patients at Week 12: • The achievement of clinical remission (by DAS28(CRP), SDAI and CDAI) ;Secondary Objectives • To assess for all patients at Week 12: • The improvement in individual components of the ACR criteria, including tender joint count (TJC), swollen joint count (SJC), Health Assessment Questionnaire-Disability Index (HAQ–DI), CRP, Patient’s Assessment of Arthritis Pain-Visual Analog Scale (VAS), Patient’s Global Assessment of Disease Activity-VAS and Physician’s Global Assessment of Disease Activity-VAS.;Secondary Objectives • To assess for all patients at Week 12: • Time to sustained ACR20 response ;Secondary Objectives • To assess for all patients at Week 12: • European League Against Rheumatism (EULAR) response ;Secondary Objectives • To assess for all patients at Week 12: • The tolerability and safety of certolizumab pegol (CZP) therapy

201091082008

1048

Inclusion Criteria:
1. Participants must be at least 18 years old at the screening visit.

2. Participants must have a diagnosis of adult–onset RA of at least three months duration as defined by the 1987 ACR classification criteria.

3. Participants must have active RA disease as defined by:

• tender joints (28 joint count) at Screening and Baseline; and

• swollen joints (28 joint count) at Screening and Baseline; and

• mg/L CRP and/or ÿmm/hour ESR (Westergren)

4. Participants must have had an unsatisfactory response or intol erance to at least one traditional DMARD.

Exclusion Criteria:
1. Participants must not have a diagnosis of any other inflammatory arthritis (e.g., psoriatic arthritis or ankylosing spondylitis).

2. Participants must not have >3 arthroplasties due to RA and/or Steinbrocker IV functional capacity.

3. Participants 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. Participants must not have a history of an infected joint prosthesis at any time with that prosthesis still in situ.

5. Participants must be free of certain mediations used for rheumatoid arthritis (analgesics,
NSAIDs /COX–2 inhibitors, oral corticosteroids, IM/IV/IA corticosteroids, IA hyaluronic
acid, DMARDs) for very specific timepoints prior to enrollment. This information can be
discussed with you.

6. Participants must not have received any experimental biological or non–biological therapy, within or outside of a clinical study in the past 3 months and sometimes longer depending on the drug.

7. Participants must not have received any biological therapy for RA within the two months prior to the Baseline visit, except for etanercept or anakinra for which a one-month washout prior to the Baseline visit is acceptable.

8. Participants 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.



9. Participants must not have received treatment with more than 2 anti-TNF agent prior to enrollment in this study.

10. Participants must not have received treatment with rituximab and/or abatacept.

11. You cannot be breast-feeding, pregnant, or plan to become pregnant during the study or within twelve weeks following last dose of study drug.

12. Participants 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.

13. Participants with active TB (or history of active TB), positive chest X–ray for TB, positive (defined as induration of ÿ 5mm) PPD skin test or patients having close contact with an individual with active TB. Patients having a PPD skin test ÿ 5 mm can enter the study, provided that active TB is excluded and provided that they are adequately treated for latent TB (e.g., isonicotinic acid hydrazide [INH therapy] for 9 months [with vitamin B6]) and provided that treatment is initiated at least 1 month prior to first administration of CZP.

14. Participants 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).

15. Participants with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease.

16. Participants with known concurrent acute or chronic viral hepatitis B or C.

17. Participants with known human immunodeficiency virus (HIV) infection.

18. Participants 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).

19. 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).

20. Patients with a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease.

21. Participants with class III or IV congestive heart failure according to the New York Heart Association (NYHA) 1964 classification criteria.

22. Participants with a history of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis).

23. Participants with a history of an adverse reaction to PEG.

24. Participants with any other condition (e.g., clinically significant laboratory values) which in the Investigator’s judgment would make the patient unsuitable for inclusion in the study.



9. Participants must not have received treatment with more than 2 anti-TNF agent prior to enrollment in this study.

10. Participants must not have received treatment with rituximab and/or abatacept.

11. You cannot be breast-feeding, pregnant, or plan to become pregnant during the study or within twelve weeks following last dose of study drug.

12. Participants 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.

13. Participants with active TB (or history of active TB), positive chest X–ray for TB, positive (defined as induration of ÿ 5mm) PPD skin test or patients having close contact with an individual with active TB. Patients having a PPD skin test ÿ 5 mm can enter the study, provided that active TB is excluded and provided that they are adequately treated for latent TB (e.g., isonicotinic acid hydrazide [INH therapy] for 9 months [with vitamin B6]) and provided that treatment is initiated at least 1 month prior to first administration of CZP.

14. Participants 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).

15. Participants with a history of a lymphoproliferative disorder including lymphoma or signs and symptoms suggestive of lymphoproliferative disease.

16. Participants with known concurrent acute or chronic viral hepatitis B or C.

17. Participants with known human immunodeficiency virus (HIV) infection.

18. Participants 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).

19. 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).

20. Patients with a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease.

21. Participants with class III or IV congestive heart failure according to the New York Heart Association (NYHA) 1964 classification criteria.

22. Participants with a history of, or suspected, demyelinating disease of the central nervous system (e.g., multiple sclerosis or optic neuritis).


23. Participants with a history of an adverse reaction to PEG.

24. Participants with any other condition (e.g., clinically significant laboratory values) which in the Investigator’s judgment would make the patient unsuitable for inclusion in the study.
23. Parti

In this study there will be two groups; one active medication group (receiving certolizumab pegol in addition to current therapy, if any) and one control group (receiving placebo in addition to current therapy, if any).

Your assignment to one of the two groups will be done randomly by a computer (after a phone call to a central system, you will be assigned to one of two treatment groups, like a flip of a coin).

There is a 4 in 5 chance that you will be randomly assigned to the active medication group and a 1 in 5 chance that you will be assigned to the placebo group. A

Ruth Kadanoff, M.D.,Ph.D.

(708) 216-2026