Comparative, Multicenter Study in Subjects with Rheumatoid Arthritis, ALVOFLEX (ALVOFLEX)

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

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: AVT05 (proposed biosimilar to golimumab); Biological: Simponi (Golimumab)

• Study Type: Interventional
• Enrollment (Actual): 502
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4001
    • Rheumatology clinic, University Multiprofile Hospital for Active Treatment Kaspela

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVT05; 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); AVT05 is a recombinant human IgG1қ mAb developed as a subcutaneous injection
Active Comparator: Simponi; 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); AVT05 is a recombinant human IgG1қ mAb developed as a subcutaneous injection; Biological: Simponi (Golimumab); Simponi (Golimumab) is a recombinant human IgG1қ mAb developed as a subcutaneous injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alvotech Swiss AG
• Investigators: Study Director: Richard Bucknall, Alvotech Swiss AG

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2023
• Primary Completion (Actual): March 4, 2024
• Study Completion (Actual): September 24, 2024

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• 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; Anti-Inflammatory Agents; Immunosuppressive Agents; Immunologic Factors; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal; Golimumab
• Other Study ID Numbers: AVT05-GL-C01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No