A Study Of CinnoRA (Adalimumab-CinnaGen) And Adalimumab (Humira) In Healthy Subjects

NCT03273192 | Completed Phase 1

• 1 other identifier: ADA.CIN.AJ.95 (I-PK)
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to demonstrate pharmacokinetic (PK) similarity of biosimilar candidate CinnoRA® relative to adalimumab reference product (Humira®) and evaluate safety and tolerability of CinnoRA®, in a parallel fashion in healthy volunteers after administration of a single dose (40 mg) of adalimumab. The primary objective of this study is to demonstrate that the PK of CinnoRA® is similar to its originator, Humira®, as assessed by the area under the serum concentration time curve (AUC) from time 0 extrapolated to infinity (AUCinf) and the Cmax. The secondary objectives of the study are:

• To further compare the PK of CinnoRA® and Humira®.
• To assess the safety of CinnoRA®.

Conditions

Bioequivalence; Phase 1

Keywords

healthy subjects; adalimumab; single dose; Phase 1; PK

Outcome Measures

Primary Outcomes (2)

• Area under the concentration-time curve from time zero to infinity (AUCinf)

  AUCinf will be calculated using the equation:AUCinf= AUClast + (Clast / Kel)

  71 days

• Maximum serum concentration (Cmax)

  It is obtained directly from the observed concentration-time data

  71 days

Secondary Outcomes (2)

• Area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast)

  71 days

• Time to Cmax (Tmax)

  71 days

Study Arms (2)

CinnaGen adalimumab

EXPERIMENTAL

CinnoRA® (adalimumab auto-injector devices produced by CinnaGen Company) 40 mg/0.8 ml in auto-injector devices A single 40-mg dose of Adalimumab was subcutaneously administered to healthy subjects.

Drug: Adalimumab

AbbVie adalimumab

ACTIVE COMPARATOR

Humira® (adalimumab auto-injector devices produced by AbbVie Company) 40 mg/0.8 ml in auto-injector devices A single 40-mg dose of Adalimumab was subcutaneously administered to healthy subjects.

Drug: Adalimumab

Interventions

Adalimumab DRUG

A single 40-mg dose of Adalimumab is administered subcutaneously to all the subjects.

Also known as: CinnoRA, Humira

AbbVie adalimumab; CinnaGen adalimumab

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide signed ICF to participate in the trial and to comply with the trial procedures.
• Be healthy male and female between the ages of 18 and 45 years. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, complete physical examination including blood pressure and heart rate measurement, 12 lead ECG and clinical laboratory tests.
• Have a Body Mass Index (BMI) of 19.0 to 30.5 kg/m2;
• Have Chest X ray with no evidence of current active TB or previous (inactive) TB, general infections, heart failure, malignancy, or other clinically significant abnormalities taken at Screening or within 24 weeks prior to Day 1 and read by a qualified radiologist.
• Female subjects with child-bearing potential must agree to use a medically accepted method of contraception during the trial and one month after the end of the trial. Acceptable methods of contraception include the following:
• Stable oral/transdermal/injectable hormonal contraceptive regimen without break through uterine bleeding and condom/spermicide.
• Intrauterine device (inserted at least 2 months prior to screening visit) used with spermicide/condom.
• Condom (male or female) with spermicide
• Vasectomy of the male partner in conjunction with condom or spermicide.

You may not qualify if:

• Being doubtful about their availability to complete the trial.
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (Multiple sclerosis), autoimmune, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Previous history of cancer, except for adequately treated basal cell or squamous cell carcinoma of the skin.
• Active or latent Tuberculosis or who have a history of Tuberculosis
• History of invasive systemic fungal infections or other opportunistic infections
• Systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process
• Serious infection associated with hospitalisation and/or which required intravenous antibiotics
• History of and/or current cardiac disease
• Have received live vaccine(s) within 4 weeks prior to Screening or who will require live vaccine(s) between Screening and the final study visit
• Intake medication with a half-life \> 24 h within 4 weeks or 5 half-lives of the medication prior to investigational product administration
• Have a history of smoking \>10 cigarettes per day.

Sponsors & Collaborators

• Cinnagen: lead

Study Sites (1)

Orchidpharmed PK/PD site

Tehran, 1425614985, Iran

Location

Related Publications (7)

• Kaur P, Chow V, Zhang N, Moxness M, Kaliyaperumal A, Markus R. A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab. Ann Rheum Dis. 2017 Mar;76(3):526-533. doi: 10.1136/annrheumdis-2015-208914. Epub 2016 Jul 27.

  PMID: 27466231 BACKGROUND

• Hyland E, Mant T, Vlachos P, Attkins N, Ullmann M, Roy S, Wagner V. Comparison of the pharmacokinetics, safety, and immunogenicity of MSB11022, a biosimilar of adalimumab, with Humira((R)) in healthy subjects. Br J Clin Pharmacol. 2016 Oct;82(4):983-93. doi: 10.1111/bcp.13039. Epub 2016 Jul 28.

  PMID: 27285856 BACKGROUND

• Ma VY, Chan L, Carruthers KJ. Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Arch Phys Med Rehabil. 2014 May;95(5):986-995.e1. doi: 10.1016/j.apmr.2013.10.032. Epub 2014 Jan 21.

  PMID: 24462839 BACKGROUND

• Davatchi F, Jamshidi AR, Banihashemi AT, Gholami J, Forouzanfar MH, Akhlaghi M, Barghamdi M, Noorolahzadeh E, Khabazi AR, Salesi M, Salari AH, Karimifar M, Essalat-Manesh K, Hajialiloo M, Soroosh M, Farzad F, Moussavi HR, Samadi F, Ghaznavi K, Asgharifard H, Zangiabadi AH, Shahram F, Nadji A, Akbarian M, Gharibdoost F. WHO-ILAR COPCORD Study (Stage 1, Urban Study) in Iran. J Rheumatol. 2008 Jul;35(7):1384. Epub 2008 May 1.

  PMID: 18464299 BACKGROUND

• Wong M, Ziring D, Korin Y, Desai S, Kim S, Lin J, Gjertson D, Braun J, Reed E, Singh RR. TNFalpha blockade in human diseases: mechanisms and future directions. Clin Immunol. 2008 Feb;126(2):121-36. doi: 10.1016/j.clim.2007.08.013. Epub 2007 Oct 3.

  PMID: 17916444 BACKGROUND

• Wiens A, Correr CJ, Venson R, Otuki MF, Pontarolo R. A systematic review and meta-analysis of the efficacy and safety of adalimumab for treating rheumatoid arthritis. Rheumatol Int. 2010 Jun;30(8):1063-70. doi: 10.1007/s00296-009-1111-4. Epub 2009 Aug 26.

  PMID: 19707765 BACKGROUND

• Jamshidi A, Sabzvari A, Anjidani N, Shahpari R, Badri N. A randomized phase I pharmacokinetic trial comparing the potential biosimilar adalimumab (CinnoRA(R)) with the reference product (Humira(R)) in healthy volunteers. Expert Opin Investig Drugs. 2020 Mar;29(3):327-331. doi: 10.1080/13543784.2020.1723000. Epub 2020 Jan 30.

  PMID: 31985294 DERIVED

MeSH Terms

Interventions

Adalimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Somayeh Amini, PharmD

  Orchid Pharmed Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2017
• First Posted: September 6, 2017
• Study Start: October 22, 2016
• Primary Completion: August 6, 2017
• Study Completion: August 6, 2017
• Last Updated: September 19, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

IR (1)