Study to Demonstrate Non-Inferior Efficacy and Safety of CinnoRA® Versus Humira® for Treatment of Active RA

NCT03172325 | Completed Phase 3 Results

• 2 other identifiers: ADA.CIN.AJ94IRCT2015030321315N1
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

Active Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With DAS28-EULAR Good and Moderate Responses at 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))

  Week 24

Secondary Outcomes (4)

• 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

Study Arms (2)

CinnaGen adalimumab

EXPERIMENTAL

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.

Drug: Adalimumab; Drug: Methotrexate; Drug: Folic Acid; Drug: Prednisolone

AbbVie adalimumab

ACTIVE COMPARATOR

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.

Drug: Adalimumab; Drug: Methotrexate; Drug: Folic Acid; Drug: Prednisolone

Interventions

Adalimumab DRUG

40 mg Adalimumab every other week is administered subcutaneously to all the patients.

AbbVie adalimumab; CinnaGen adalimumab

Methotrexate DRUG

15 mg Methotrexate is weekly administered to all the patients.

AbbVie adalimumab; CinnaGen adalimumab

Folic Acid DRUG

At least 1 mg Folic acid is daily administered to all the patients.

AbbVie adalimumab; CinnaGen adalimumab

Prednisolone DRUG

7.5 mg Prednisolone is daily administered to all the patients.

AbbVie adalimumab; CinnaGen adalimumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Cinnagen: lead

Study Sites (10)

Alzahra Hospital

Isfahan, Iran

Location

Besat 4 Clinic

Kerman, Iran

Location

Ghaem Hospital

Mashhad, Iran

Location

Razi Hospital

Rasht, Iran

Location

Imam Ali Clinic

Shahr-e Kord, Iran

Location

Hafez Hospital

Shiraz, Iran

Location

Noor Medical Complex

Tabriz, Iran

Location

Imam Reza Hospital (501 Artesh)

Tehran, Iran

Location

Iran Rheumatism Center

Tehran, Iran

Location

Loghman Hakim Hospital

Tehran, Iran

Location

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  PMID: 28728599 RESULT

MeSH Terms

Interventions

Adalimumab; Methotrexate; Folic Acid; Prednisolone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Nassim Anjidani
• Organization: CinnaGen Co.

anjidani.n@orchidpharmed.com

00989125477964

Study Officials

• Ahmadreza Jamshidi, Professor

  Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: June 1, 2017
• Study Start: November 18, 2015
• Primary Completion: August 17, 2016
• Study Completion: January 4, 2017
• Last Updated: February 2, 2021
• Results First Posted: February 2, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

IR (10)