A Phase III, Randomized, Two-armed, Double-blind, Parallel, Active Controlled Clinical Trial to Determine the Non-inferior Efficacy and Safety of CinnoRA® (Adalimumab, CinnaGen Co.) Versus Humira® for Treatment of Active RA
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Cinnagen
- 入组人数
- 136
- 试验地点
- 10
- 主要终点
- Percentage of Patients With DAS28-EULAR Good and Moderate Responses at Week 24
研究概览
简要总结
The purpose of this study is to compare the efficacy and safety of adalimumab produced by CinnaGen company and AbbVie adalimumab in subjects with active Rheumatoid Arthritis. Patients with the diagnosis of active Rheumatoid arthritis according to EULAR criteria (European League Against Rheumatism) aged between 18 to 75 years will be included. This study is a Phase III, randomized, two arms, double-blind (patient and assessor blinded), parallel active-controlled non-inferiority clinical trial. The eligible patients are randomized in a 1:1 ratio to receive CinnoRA® or Humira®. Every two weeks, 40 mg of either of the drugs will be administered to each patient subcutaneously along with methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over six months.
The primary objective of the study is to compare the efficacy of test- adalimumab (CinnoRA®) and the reference adalimumab (Humira®) in patients with moderately to severely active rheumatoid arthritis regarding the evaluation of EULAR criteria based on Disease activity score (DAS).
The secondary objectives of this study are:
- To further compare the efficacy of test- adalimumab to reference adalimumab
- To assess the safety of test- adalimumab compared to reference adalimumab
详细描述
The purpose of this study is to compare the efficacy and safety of Adalimumab produced by CinnaGen company and AbbVie adalimumab in subjects with active rheumatoid arthritis. Patients with the diagnosis of active rheumatoid arthritis according to EULAR criteria (European League Against Rheumatism) aged between 18 to 75 years will be included. This study is a Phase III, randomized, two arms, double-blind (patient and assessor blinded), parallel active-controlled non-inferiority clinical trial. The eligible patients will be randomized in a 1:1 ratio to receive CinnoRA® or Humira®. Every two weeks, 40 mg of either of the drugs will be administered to each patient subcutaneously along with methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over six months.
Physical examinations, vital signs, disease activity, and laboratory parameters will be evaluated for patients at baseline and 3 and 6-month visits. The incidence of adverse events at each visit will be recorded based on patients' reports, vital signs, physical examinations, and laboratory tests.
The trial is reviewed by food and drug administration of Iran. The protocol, case report form (CRF), information for patients, and informed consent form are submitted to the ethics committees responsible for review and approval purposes, according to national regulatory guidelines.
In this study, no patient will be recruited without an informed consent form. All the informed consent forms which will be signed by the patients will have two copies so that patients can receive a copy of it.
Determination of sample size:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18-75 years at the time of signing the informed consent form.
- •Have been diagnosed as having active rheumatoid arthritis (RA) according to The European League Against Rheumatism criteria
- •moderately to severely active RA for at least six months
- •Patients who have an inadequate response to the treatment with the usual non-biological regimen for at least 12 weeks according to their investigator judgment.
- •Ability to comprehend and willingness to sign the Informed Consent Form for this study.
排除标准
- •Tuberculosis patient or latent tuberculosis patient (PPD >5mm or abnormal Chest X-ray)
- •Have been treated previously with any biological agents including any tumor necrosis factor inhibitors (including ORENCIA® (abatacept), KINERET® (anakinra), REMICADE® (infliximab), ENBREL® (etanercept), CIMZIA® (certolizumab pegol), SIMPONI® (golimumab), or Adalimumab).
- •Have a known hypersensitivity to human immunoglobulin proteins or other components of Humira or test- Adalimumab
- •Women who are pregnant, breastfeeding or planning to become pregnant during the study
- •Have a positive serological test for hepatitis B or hepatitis C or have a known history of infection with human immunodeficiency virus (HIV) of the past three months.
- •Physical incapacitation (ACR functional Class IV or wheelchair-/bed-bound)
- •Have had a serious infection or have been treated with intravenous antibiotics for an infection within eight weeks or oral antibiotics within two weeks prior to screening
- •Have a history of chronic or recurrent infection
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > two times upper limit of normal.
- •Hemoglobin <8.5 g/dL.
- •Platelets <125,000/µL.
- •Leukocyte count <3500/µL.
- •Serum Creatinine>2 mg/dl
- •Concomitant use of Prednisolone > 10 mg/day and NSAIDs
- •Treatment with intravenous, intramuscular, intra-articular and oral corticosteroids within four weeks prior to Day 1 (prednisolone, more than 7.5 mg/daily)
- •Ever used RITUXAN® (rituximab), IMURAN® (azathioprine), or PURINETHOL® (mercaptopurine, 6-MP).
- •Have any of the following conditions:
- •History of congestive heart failure.
- •History of acute myocardial infarction or unstable angina within the previous 12 months prior to Screening.
- •History of demyelinating disorders (e.g., MS)
- •History of multiple sclerosis
- •History of any malignancy within the previous five years prior to Screening.
- •Any other disease or disorder which, in the opinion of the Investigator, will put the subject at risk if they are enrolled.
研究组 & 干预措施
CinnaGen adalimumab
CinnoRA® (adalimumab Prefilled Syringe produced by CinnaGen Company) 40 mg/0.8 ml Every other week 40 mg Adalimumab, will be subcutaneously administered to rheumatic patients during six months. Along with, 15 mg weekly methotrexate, at least 1 mg daily Folic acid and 7.5 mg daily Prednisolone over six months.
干预措施: Adalimumab (Drug)
CinnaGen adalimumab
CinnoRA® (adalimumab Prefilled Syringe produced by CinnaGen Company) 40 mg/0.8 ml Every other week 40 mg Adalimumab, will be subcutaneously administered to rheumatic patients during six months. Along with, 15 mg weekly methotrexate, at least 1 mg daily Folic acid and 7.5 mg daily Prednisolone over six months.
干预措施: Methotrexate (Drug)
CinnaGen adalimumab
CinnoRA® (adalimumab Prefilled Syringe produced by CinnaGen Company) 40 mg/0.8 ml Every other week 40 mg Adalimumab, will be subcutaneously administered to rheumatic patients during six months. Along with, 15 mg weekly methotrexate, at least 1 mg daily Folic acid and 7.5 mg daily Prednisolone over six months.
干预措施: Folic Acid (Drug)
CinnaGen adalimumab
CinnoRA® (adalimumab Prefilled Syringe produced by CinnaGen Company) 40 mg/0.8 ml Every other week 40 mg Adalimumab, will be subcutaneously administered to rheumatic patients during six months. Along with, 15 mg weekly methotrexate, at least 1 mg daily Folic acid and 7.5 mg daily Prednisolone over six months.
干预措施: Prednisolone (Drug)
AbbVie adalimumab
Humira® (adalimumab Prefilled Syringe produced by AbbVie Company) 40 mg/0.8 ml Every other week 40 mg Adalimumab, will be subcutaneously administered to rheumatic patients during six months. Along with, 15 mg weekly methotrexate, at least 1 mg daily Folic acid and 7.5 mg daily Prednisolone over six months.
干预措施: Adalimumab (Drug)
AbbVie adalimumab
Humira® (adalimumab Prefilled Syringe produced by AbbVie Company) 40 mg/0.8 ml Every other week 40 mg Adalimumab, will be subcutaneously administered to rheumatic patients during six months. Along with, 15 mg weekly methotrexate, at least 1 mg daily Folic acid and 7.5 mg daily Prednisolone over six months.
干预措施: Methotrexate (Drug)
AbbVie adalimumab
Humira® (adalimumab Prefilled Syringe produced by AbbVie Company) 40 mg/0.8 ml Every other week 40 mg Adalimumab, will be subcutaneously administered to rheumatic patients during six months. Along with, 15 mg weekly methotrexate, at least 1 mg daily Folic acid and 7.5 mg daily Prednisolone over six months.
干预措施: Folic Acid (Drug)
AbbVie adalimumab
Humira® (adalimumab Prefilled Syringe produced by AbbVie Company) 40 mg/0.8 ml Every other week 40 mg Adalimumab, will be subcutaneously administered to rheumatic patients during six months. Along with, 15 mg weekly methotrexate, at least 1 mg daily Folic acid and 7.5 mg daily Prednisolone over six months.
干预措施: Prednisolone (Drug)
结局指标
主要结局
Percentage of Patients With DAS28-EULAR Good and Moderate Responses at Week 24
时间窗: Week 24
The primary variables are the percentage of patients with DAS28-EULAR Good and Moderate Responses at week 24 compared with Humira. Moderate response is defined as decrement of more than 1.2 in patient's DAS score while patient's DAS score is equal to or more than 3.2 or decrement of 0.6-1.2 while patient's DAS score is equal to or below 5.1. Good response is defined as decrement of more than 1.2 in patient's DAS score while patient's DAS score is below 3.2. We used the Disease Activity Score-28 for rheumatoid arthritis with erythrocyte sedimentation rate (DAS28-ESR) to assess disease activity in patients with rheumatoid arthritis. This score ranges from 2 to 10, and higher values indicate higher disease activity. DAS28-ESR is calculated with the following formula: DAS28-ESR= (0.56\*√(Tender Joint Count)+0.28\*√(Swollen Joint Count)+0.7\*ln(ESR)+0.014\*(global health))
次要结局
- Percentage of Patients Achieving ACR20, ACR50 and ACR70 Response Rates at Week 24(Week 24)
- Health Assessment Questionnaire (HAQ) Disability Index at Week 24.(Week 24)
- The Incidence of Adverse Events(From the time of first treatment up to the last dose of study treatment; 24 weeks.)
- Immunogenicity: Number of Participants With Anti-Drug Antibodies (ADA)(Week 24)