Comparative, Multicenter Study in Subjects With Rheumatoid Arthritis, ALVOFLEX

Study Overview
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Brief Summary
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This is a study to compare the efficacy, safety and immunogenicity of AVT05 versus EU-Simponi® in combination with methotrexate (MTX) in subjects with moderate to severe rheumatoid arthritis (RA). The study will consist of up to 4-week Screening Period, a 48-week Treatment Period, and a 4-week Safety Follow-up Period.

Official Title
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Randomized, Double-blind, 2-arm Multicenter Study to Investigate the Efficacy, Safety and Immunogenicity Between Subcutaneous AVT05 and EU-approved Simponi® in Subjects With Moderate to Severe Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: AVT05 (proposed biosimilar to golimumab)
* Biological: Simponi (Golimumab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed with active RA according to ACR/EULAR 2010 classification criteria Subjects diagnosed with moderately to severe active RA as defined by ≥ 6 swollen (out of 66) and ≥6 tender (out of 68) joint counts, CRP >1mg/l and with at least one of positive rheumatoid factor, positive anti-citrullinated peptide antibodies and/or evidence of 1 joint erosion of hands, wrist of dominant hand or feet at screening Subjects must have taken methotrexate for ≥12 weeks Exclusion Criteria: Prior treatment with biologics or Janus kinase inhibitors that may be used as disease-modifying anti-rheumatic drugs Any past or concurrent medical conditions that could potentially increase the subject's risks or that would interfere with the study evaluation, procedures or study completion Major chronic inflammatory disease or connective tissue disease other than RA or any active autoimmune disease Presence of chronic obstructive pulmonary disease Presence of chronic heart failure NYHA class III or IV

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVT05<br>AVT05 is the proposed biosimilar to Simponi. Subjects in this arm will receive AVT05 50mg s.c. every 4 weeks until week 48. Intervention: Biological: Golimumab | Biological: AVT05 (proposed biosimilar to golimumab)<br>* AVT05 is a recombinant human IgG1қ mAb developed as a subcutaneous injection<br>|
| Active Comparator: Simponi<br>Subjects in this arm will receive EU Simponi 50mg s.c. every 4 weeks until week 12. At week 16 responders will be re-randomized in a 1:1 ratio to receive either: AVT05 50mg s.c. every 4 weeks until week 48 Simponi 50mg s.c. every 4 weeks until week 48 Intervention: Biological: Golimumab | Biological: AVT05 (proposed biosimilar to golimumab)<br>* AVT05 is a recombinant human IgG1қ mAb developed as a subcutaneous injection<br>Biological: Simponi (Golimumab)<br>* Simponi (Golimumab) is a recombinant human IgG1қ mAb developed as a subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate comparative efficacy of AVT05 with EU-approved Simponi as measured by DAS28-CRP at week 16. | Change from baseline in DAS28-CRP response criteria at week 16 | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess additional efficacy measures of AVT05 and EU-Simponi in terms of DAS28-CRP | Change from baseline in DAS28-CRP response criteria at weeks 4, 8, 12, 24, 32, 40, 48 and 52 | Weeks 4, 8, 12, 24, 32, 40, 48 and 52 | 
| Assess additional efficacy measures of AVT05 and EU-Simponi in terms of ACR20/50/70 and its individual components throughout the study | Percentage of subjects achieving ACR20/50/70 at weeks 4, 8, 12, 16, 24, 32, 40, 48 and 52 | Weeks 4, 8, 12, 16, 24, 32, 40, 48 and 52 |