A Phase III Study to Evaluate the Efficacy and Safety of ENIA11 in Combination With Methotrexate Versus Methotrexate Alone in Patients With RA (ENIA11)

A Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicentre, Phase III Study to Evaluate the Efficacy and Safety of ENIA11 in Combination With Methotrexate Versus Methotrexate Alone in Patients With Rheumatoid Arthritis

A Prospective, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicentre, Phase III Study to Evaluate the Efficacy and Safety of ENIA11 in Combination with Methotrexate versus Methotrexate Alone in Patients with Rheumatoid Arthritis

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Methotrexate; Drug: ENIA11; Drug: Placebo

Detailed Description

The objectives of the study are to evaluate the efficacy and safety of ENIA11 in combination with methotrexate versus methotrexate alone in patients with rheumatoid arthritis.

This is a multi-center, double-blind, randomized, parallel-group, placebo-controlled study to evaluate the efficacy and safety of ENIA11 in combination with methotrexate versus methotrexate alone in patients with rheumatoid arthritis.

Subject participation duration: A total of 28 weeks, including: 2 weeks of screening, 24 weeks of treatment and 2 weeks of follow-up

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Changhua, Taiwan
    • Changhua Christian Hospital
  • Chiayi City, Taiwan
    • Buddhist Tzu Chi General Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Veterans General Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Chung Shan Medical University Hospital
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • Taipei City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients aged ≥ 20 years old;
2. Patient meet ACR criteria for rheumatoid arthritis over 6 month duration;
3. Patient with active disease at the time of screening as defined by six or more swollen joints and six or more tender joints;

4. Presence of at least one of the following criteria:

   • Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/h,
   • C-Reactive Protein (CRP) ≥ 10 mg/L,
5. RA functional class I, II, or III;
6. Patients have been treated on methotrexate for at least 3 month, and maintained at stable dose of 15-25 mg/week for at least 8 weeks; MTX low dose as 10 mg per week is allowed for patients who had a documented history of constitutional symptoms at higher doses.
7. Patient is willing and able to comply with study procedures and sign informed consent.

Exclusion Criteria:

1. Active autoimmune disease (other than RA) requiring immunosuppressive therapy;
2. In the opinion of the investigator, the patient shows persistent signs of immunosuppression;
3. Known hypersensitivity to etanercept or ENIA11 or any of its components;
4. Previous unsuccessful treatment with etanercept, anti-TNF monoclonal antibodies or a soluble TNF receptor (e.g., infliximab);
5. Suspected or diagnosed pulmonary tuberculosis, or other chronic or current infectious disease at discretion of investigator;
6. Patients who have a history or evidence of a medical condition that would expose them to an undue risk of a significant adverse event during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, immune, neurological, hematological, gastrointestinal or psychiatric disease as determined by the clinical judgment of the investigator;
7. Patients with any of the following laboratory abnormalities: ALT/AST > 3 times ULN, creatinine > 2 mg/dl, WBC < 3,000/mm3, Hgb < 8.5 g/dL, platelet count < 100,000/mm3;
8. Patients have received live attenuated vaccination program within 3 months or BCG vaccine within 12 months prior enrollment;

9. Female patient of childbearing potential who:

   • is lactating; or
   • has positive urine pregnancy test at Visit 1; or
   • refuse to adopt reliable method of contraception during the study;
10. Diagnosis of primary fibromyalgia or other joint inflammatory disease including but not limited to gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease;
11. Known or suspected positive serology for human immunodeficiency, hepatitis B or C virus;
12. Patient has received any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of investigational product;
13. Patient has history of substance abuse, drug addiction or alcoholism;
14. Patient who have had participated in prior phase I/II clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: methotrexate & ENIA11; ENIA11 25 mg, sc twice weekly	Drug: Methotrexate; Methotrexate 15-25 mg/week; Drug: ENIA11; ENIA11 25 mg, sc twice weekly; Other Names: TuNEX
Active Comparator: methotrexate & Placebo; Placebo, sc twice weekly	Drug: Methotrexate; Methotrexate 15-25 mg/week; Drug: Placebo; Placebo, sc twice weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20 responder at last treatment visit	The primary efficacy endpoint is defined as ACR20 responder at last treatment visit (Week 24).	Week 24

Collaborators and Investigators

• Sponsor: Mycenax Biotech Inc.
• Investigators: Principal Investigator: Joung-Liang Lan, PHD, China Medical University Hospital; Principal Investigator: Chung-Ming Huang, MD, China Medical University Hospital; Principal Investigator: Der-Yuan Chen, PHD, Taichung Veterans General Hospital; Principal Investigator: Ling-Ying Lu, PHD, Kaohsiung Veterans General Hospital.; Principal Investigator: Ning-Sheng Lai, PHD, Buddhist Tzu Chi General Hospital; Principal Investigator: Tien-Tsai Cheng, MD, Chang Gung Memorial Hospital; Principal Investigator: Gregory J Tsay, PHD, Chung Shan Medical University; Principal Investigator: Ying-Ming Chiu, MD, Changhua Christian Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): December 1, 2017
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 16, 2012
• First Posted (Estimate): October 18, 2012

Study Record Updates

• Last Update Posted (Actual): April 17, 2018
• Last Update Submitted That Met QC Criteria: April 13, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: TNF; RA; MTX; ENIA11
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: TSHEN1101