Efficacy and Safety of IBI303 in Adult Patients With Active Ankylosing Spondylitis

NCT ID: NCT02893254

Last Updated: 2018-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 438 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-22
• Study Completion Date: 2018-03-16

Brief Summary

Study of the efficacy and safety of IBI303 compared with adalimumab in adult patients with ankylosing spondylitis (AS) who have had an inadequate response to or who are intolerant to one or more nonsteroidal anti-inflammatory drugs (NSAIDs)

Detailed Description

Adults patients with active ankylosing spondylitis (AS) were randomized in a 1:1 ratio to receive treatment with adalimumab 40 mg every other week (eow) or IBI303, given subcutaneously (SC), in the 24-week double-blind (DB) phase. Randomized participants received one SC injection of the appropriate DB study medication (adalimumab 40 mg or IBI303) at Week 0 and then eow until Week 22. A follow-up visit occurred 70 days(Week 32) after the last dose of study drug to obtain information on any ongoing or new adverse events (AEs).

Conditions

AS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

IBI303

IBI303 40mg administered subcutaneously every other week, 12cycles

Group Type: EXPERIMENTAL

IBI303

Intervention Type: DRUG

12 cycles. IBI303: 40 mg, iH

Adalimumab

Adalimumab 40mg administered subcutaneously every other week

Group Type: ACTIVE_COMPARATOR

Adalimumab

Intervention Type: DRUG

12 cycles. Adalimumab: 40mg, iH

Interventions

IBI303

12 cycles. IBI303: 40 mg, iH

Intervention Type: DRUG

Adalimumab

12 cycles. Adalimumab: 40mg, iH

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Between 18 and 65 years of age

2. Fulfilled modified New York Criteria for AS, had active disease（as defined by≥2 of the following: Bath AS Disease Activity Index(BASDAI) ≥4(10cm VAS); total back pain≥40(100mm VAS) and ≥1 hour of morning stiffness）

3. No response, or inadequate response, or intolerant to≥1 NSAID at least 4 weeks

4. Participants who are regularly taking DMARDs(SSZ≤3g/day，MTX≤15mg/week) as part of their AS therapy are required to be on a stable dose ≥28 days prior to Baseline, and are required to be on a stable DMARDs dose and to accept oral folic acid therapy(≥5mg/week) during the study period；

5. Participants who are regularly taking NSAIDs as part of their AS therapy are required to be on a stable dose ≥14 days prior to Baseline, and are required to be on a stable dose during the study period；

6. Glucocorticoid must be withdrawn for at least 4 weeks prior to Baseline, and were not allowed during the study period.

7. Total duration of prior physical therapy should be at least 2 weeks

8. Traditional Chinese medicines to AS must be withdrawn for at least 28 days prior to Baseline, and were not allowed during the study period.

9. Biological agents must be withdrawn: etanercept and anakinra(IL-1 receptor antagonist) for at least 4 weeks prior to administration; tocilizumab(IL-6 monoclonal antibody) for at least 12 weeks prior to administration; other biological agents for 12 weeks or 5 half-lives(whichever is longer) prior to administration

10. Male subjects' partner, or female subjects should be willing to use adequate contraception from admission to clinical research center until 5 months post dosing；

11. To fully understanding the purpose of the study, to understand the pharmacological action of the study drugs and the possible adverse reactions; participants who are voluntary to sign the informed consent according to the Declaration of Helsinki

12. Blood routine examination: hemoglobin ≥90g/L, WBC count ≥3.5×109/L, PLT count ≥100×109/L; liver function examination: total bilirubin(TBIL), direct bilirubin(DBIL), aspartate transaminase(AST) or alanine aminotransferase (ALT) <1.5×ULN; kidney function examination：creatinine(Cr) ≤ULM, usea nitrogen(BUN) ≤1.25×ULN

Exclusion Criteria

1. No response to prior tumor necrosis factor-α inhibitors treatment

2. Use of DMARD(except for sulfasalazine or methotrexate) within 4 weeks prior to Baseline

3. Use of opioid analgesics(such as methadone, morphine) within 4 weeks prior to Baseline

4. X-ray suggests total spinal ankylosis, or sacroiliac joint fusion

5. Patients with moderate to severe congestive heart failure（NYHA ）

6. Has received intra-articular joint injection(s), spinal or paraspinal injection(s) with corticosteroids within 28 days prior to Baseline

7. Has undergone spinal surgery or joint surgery within 2 months prior to the administration of the study drugs

8. Patients with other rheumatic diseases or immunodeficiency, including inflammatory bowel disease(IBD), psoriasis, active uveitis

9. Recent active or chronic infection requiring anti-infective therapy, such as M.tuberculosis, Listeriosis, Histophasmosis

10. Tuberculosis(TB) history, or a positive T-SPOT test, or chest radiograph suggests active TB

11. Positive serology for human immunodeficiency virus(HIV) antibody

12. Positive serology for hepatitis C virus antibody

13. Active or chronic HBV infection, such as positive hepatitis B virus surface antigen

14. Malignancy history ≤5 years（except for successfully treated cutaneous squamous cell carcinoma, or basal cell carcinoma, or localized cervical carcinoma in situ, or breast ductal carcinoma in situ）

15. History of relevant allergy/hypersensitivity (including allergy to the study medications or its excipients)

16. Prior or recent central nervous system demyelinating disease or multiple sclerosis

17. Use of live vaccines within 3 months prior to Baseline

18. Pregnant or breastfeeding women

19. Suspected or confirmed drug/alcohol use

20. Participation in another interventional trial within 3 months prior to administration

21. Subjects with serious psychiatric or nervous system diseases, or patients who have difficulty in informing consent or AE presentation, or illiterate patients

22. Subjects who are unable to complete the study, or who may not be able to comply with the requirement of the study, judged by the investigators

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Innovent Biologics (Suzhou) Co. Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huji Xu

Role: PRINCIPAL_INVESTIGATOR

Shanghai Changzheng Hospital

References

Huang F, Gu J, Zhu P, Bao C, Xu J, Xu H, Wu H, Wang G, Shi Q, Andhivarothai N, Anderson J, Pangan AL. Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial. Ann Rheum Dis. 2014 Mar;73(3):587-94. doi: 10.1136/annrheumdis-2012-202533. Epub 2013 Mar 8.

Reference Type: RESULT

PMID: 23475983 (View on PubMed)

Xu H, Li Z, Wu J, Xing Q, Shi G, Li J, Liu X, Wu L, Li X, Tan W, He D, Bi L, Li H, Xiao Z, Shuai Z, Li X, Wang Y, Luo L, Zheng Y, Xiao W, Wu X, Zhou L, Li T, Qian L, Zhou H, Lu S, Zheng S, Xiong Y, Wang X, Wang Y, Wu X. IBI303, a biosimilar to adalimumab, for the treatment of patients with ankylosing spondylitis in China: a randomised, double-blind, phase 3 equivalence trial. Lancet Rheumatol. 2019 Sep;1(1):e35-e43. doi: 10.1016/S2665-9913(19)30013-X. Epub 2019 Aug 28.

Reference Type: DERIVED

PMID: 38229357 (View on PubMed)

Other Identifiers

CIBI303A301

Identifier Type: -

Identifier Source: org_study_id