Efficacy, Safety and Immunogenicity of Enerceptan Compared to Enbrel in Rheumatoid Arthritis

NCT03332719 | Completed Phase 3 DMC

• 1 other identifier: GEMENE001
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to asses the compared efficacy, safety and immunogenicity of ENERCEPTAN® with ENBREL® in combination with Methotrexate for the treatment of patients with rheumatoid arthritis.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• ACR (American College of Rheumatology) 20

  The percentage of patients who achieved ACR20 at Week 32 is the primary end point. Signs and symptoms are assessed with a composite rating scale of the ACR (American College of Rheumatology) that includes 7 variables: * Tender Joints Count * Swollen Joints Count * Levels of an acute phase reactant (CRP level) * Patient's assessment of pain * Patient's global assessment of disease activity * Physician's global assessment of disease activity * Patient's assessment of physical function

  32 weeks of treatment

Secondary Outcomes (11)

• ACR (American College of Rheumatology) 50

  32 weeks of treatment

• ACR (American College of Rheumatology) 70

  32 weeks of treatment

• DAS (Disease activity state)

  32 weeks of treatment

• EULAR (European League Against Rheumatism) response criteria

  32 weeks of treatment

• Time to onset of benefit

  32 weeks of treatment

Study Arms (2)

Enbrel®

ACTIVE COMPARATOR

Enbrel® 50 mg injectable solution in autoinjector SureClick® contains: 50 mg etanercept and excipients/Once a week Methotrexate 15 to 25 mg /Once a week

Biological: Etanercept; Drug: Methotrexate

Enerceptan®.

EXPERIMENTAL

Enerceptan®. Injectable Solution in prefilled syringes Source: GEMABIOTECH S. A. Formulation per unit: 1,0 ml of Enerceptan® contains 50 mg solution of Etanercept /Once a week Methotrexate 15 to 25 mg /Once a week

Biological: Etanercept; Drug: Methotrexate

Interventions

Etanercept BIOLOGICAL

Enbrel®; Enerceptan®.

Methotrexate DRUG

Enbrel®; Enerceptan®.

Eligibility Criteria

• Age: 19 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult men and women over 18 years, who present moderate to severe active RA (rheumatoid arthritis) , diagnosed according to ACR/ EULAR 2010 criteria, who have failed prior MTX (methotrexate) therapy. Functional class I to III.
• Moderate to severe disease activity, according to DAS28 (erythrosedimentation) ≥ 3.2.
• Must have at least a minimum of 6 tender joints and 8 swollen joints. If a patient has a joint surgery prior to the study, this joint is considered not evaluable throughout the study development.
• Must have at least, one erosion in the baseline radiograph. Local assessment centers either radiologist or rheumatologist to decide on this criterion will be accepted.
• Medical Indication to incorporate a biological treatment in their therapy.
• Treatment with MTX for at least 3 months on dose ≥15 mg/ week, stable over the last 28 days before the Day 1. Doses lower than 15 mg and greater or equal than 10 mg/ week are accepted in cases with previously documented intolerance.
• Subjects who have previously received treatment with a biologic (approved or investigational) except etanercept, may participate as long as the corresponding washout time has elapsed prior to the screening interview: At least
• weeks for infliximab (T1/2 8 to 9.5 days) and for tocilizumab (T1/2 3to 12 days)
• weeks for adalimumab (T1/2 10 to 20 days), Golimumab (T1/2 11 to 14 days), certolizumab (T1/2 14 days), abatacept (T1/2 14 days),
• year for Rituximab (T1/2 77,5 days)
• T1/2 for any other biological product, used for the treatment of rheumatoid arthritis, wether it has been used or not for research.
• Subjects who are receiving leflunomide must have a previous washout of 8 weeks before Day 1, except had have treatment with colestyramine, according to manufacturer indications.
• Can receive non steroidal anti inflammatory drugs (NSAIDs) or oral corticoids in doses \< 10 mg of prednisone, but treatment must have been stable over the last 28 days.
• Subjects must be able to self-inject or willing to have a previously assigned caregiver do it for them.
• Subjects must be able to meet the schedule of visits, understand and comply with other protocol requirements.

You may not qualify if:

• Simultaneous treatment with other investigational drug or participation in another clinical study that the investigator considers inadvisable.
• Women who are pregnant or breastfeeding.
• Past history of nonresponsive to TNF (tumor necrosis factor) blocking agents or other biologic treatment.
• Chronic antibiotic therapy, if the investigator considers this may affect the safety of the subject or the assessment of the study results.
• Any previous or current serious medical conditions that, in the opinion of the investigator, constitute a contraindication for the study treatment, as:
• Administration of vaccines:
• Subjects who have received a live attenuated vaccine within 3 months prior to the randomization Visit (for example, varicella-zoster, oral polio, rabies, yellow fever vaccines.)
• Subjects who have received the BCG (bacillus Calmette-Guerin) vaccine within 12 months before the Selection.
• Presence of :
• iii. Non-healing infected skin ulcers. b. In the previous time: i. Background of recurrent bacterial, viral, fungal (excluding superficial infections or nail bed mycosis), mycobacterial or other severe infections within the last month previous to selection.
• ii. Hospitalization for infection or Subjects who have received antibiotics intravenously within the last month or orally within the last 2 weeks.
• iii. Subjects with herpes zoster in the last 2 months.
• Past history of drug or alcohol abuse within the last year prior to the Screening Visit.
• Known hypersensitivity to the study drug or history of severe allergy or anaphylactic reaction to monoclonal antibodies or fusion or human proteins.
• Any condition that, in the investigator opinion, would not allow compliance with the guidelines of the study by the patient.

Sponsors & Collaborators

• Gema Biotech S.A.: lead
• QUID Quality in Drugs and Devices Latin American Consulting SRL: collaborator

Study Sites (1)

Instituto Medico CER

Bs As, Argentina

Location

Related Publications (1)

• Strusberg I, Mysler E, Citera G, Siri D, de Los Angeles Correa M, Lazaro MA, Pardo Hidalgo R, Spindler A, Tate P, Venarotti H, Velasco Zamora J, Klimovsky E, Federico A, Scheines E, Gonzalez E, Cordeiro L, Lago N. Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis: A Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study. J Clin Rheumatol. 2021 Sep 1;27(6S):S173-S179. doi: 10.1097/RHU.0000000000001616.

  PMID: 33337815 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Etanercept; Methotrexate

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jorge Velasco, MD

  Instituto Médico CER

  PRINCIPAL INVESTIGATOR

• Maria de los Angeles Correa, MD

  PAMPA

  PRINCIPAL INVESTIGATOR

• Maria Alicia Lazaro, MD

  IARI

  PRINCIPAL INVESTIGATOR

• Rodolfo Pardo Hidalgo, MD

  CER San Juan

  PRINCIPAL INVESTIGATOR

• Daniel Siri, MD

  CAICI

  PRINCIPAL INVESTIGATOR

• Alberto Jorge Spindler, MD

  Centro Médico Privado de Reumatología

  PRINCIPAL INVESTIGATOR

• Ingrid Strusberg, MD

  Centro Reumatologico Strusberg

  PRINCIPAL INVESTIGATOR

• Patricio Tate, MD

  OMI

  PRINCIPAL INVESTIGATOR

• Horacio Oscar Venarotti, MD

  Atención Integral en Reumatología

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2016
• First Posted: November 6, 2017
• Study Start: February 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: September 1, 2017
• Last Updated: November 6, 2017

Record last verified: 2017-10

Locations

AR (1)