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

September 18, 2018 updated by: Cinnagen

A Randomised, Double-blind, Single-dose, Parallel-group Study in Healthy Subjects to Demonstrate Pharmacokinetic Equivalence of CinnoRA® (Produced by CinnaGen CO.) and Humira® (the Reference Drug, Produced by AbbVie Inc.)

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®.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a single-dose trial with one administration of each product (CinnoRA® and Humira®). Each subject will participate in one treatment period, and will be randomised to receive CinnoRA® or Humira® in a parallel fashion. The subjects will be closely monitored during the following 24 hours (h), and will be allowed to leave the site in the next morning post evaluation and blood samples will be collected prior to and at the following time points after the dose: 4, 8, 12 and 24 hours post-dose (on day 2). The subjects will be requested to visit the trial site on days 3, 4, 5, 6, 7, 8, 9, 12, 15, 22, 29, 36, 43, 50, 57, 63 and 71 after dose for blood sampling and evaluation of safety variable and tolerability.

Before initiation, the trial is reviewed by food and drug administration of Iran. The protocol, case report form (CRF), information for subjects and informed consent form are submitted to the ethics committees responsible for review and approval purposes, according to national regulatory guidelines.

In this study, no subject is recruited without an informed consent. All the informed consent forms which are signed by the subjects have two copies so that subjects could receive a copy of it.

This is a single-dose trial with one administration of each product (CinnoRA® and Humira®). 74 (group A=37, group B=37) eligible subjects have been planned to enter to the study. All of whom are aged between 18 and 45 years. Subjects' randomization was done, using permuted block randomization method. Both groups received 40 mg of either of the drugs as a single subcutaneous injection. The injection method, injection pens and cartridges were totally the same in both groups. 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. Secondary objectives include assessment of the time to Cmax (tmax), AUC from time 0 to the last quantifiable concentration (AUClast) of CinnoRA® compared with Humira®, as well as evaluation of safety and tolerability. The safety endpoints of the trial are to evaluate the incidence of reported adverse effects, detecting changes in vital signs, clinical laboratory tests (hematologic, biochemistry, urine analysis and urine culture tests) and ECG.

Determination of sample size:

An equivalence test of means AUCinf using two one-sided tests on data from a parallel-group design with sample sizes of 37 in the reference group and 37 in the treatment group achieves 81% power at a 10% significance level when the true ratio of the means AUCinf is 1.00, the coefficient of variation on the original, unlogged scale is 0.38, and the equivalence limits of the mean ratio AUCinf are 0.80 and 1.25.

DATA QUALITY ASSURANCE:

CinnaGen Company conducts clinical trials according to procedures that incorporate the ethical principles of GCP. Accurate and reliable data collection was assured by verification and cross-check of the CRFs against the subject's records by clinical monitors (source document verification was performed), and the maintenance of a drug-dispensing log by the center. A comprehensive validation check program was used to verify the data, and discrepancy reports were generated accordingly for resolution by the investigator.

Blinding:

This is a double-blind trial. During the clinical phase of the trial, neither the subjects nor the site personnel are aware of the identity (CinnoRA® and Humira®) of the treatments administered. However, there is an unblinded person who receives the randomisation list and dispenses the trial drugs according to the list. The unblinded person is not otherwise participate in the execution of the trial. The randomisation list determines the dispensing order of the trial products for each subject and only the randomisation number appear on the sample collection logs, as well as, on the sample aliquots delivered to the bioanalytical laboratory. Thus, the personnel responsible for analysing the PK samples are also be blinded.

Randomisation envelopes are stored in the ISF, in a locked cabinet. In a case of emergency, the code of an individual subject may be opened and the reasons for opening will be documented and the subject will be discontinued from the trial

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Provide signed ICF to participate in the trial and to comply with the trial procedures.
  2. 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.
  3. Have a Body Mass Index (BMI) of 19.0 to 30.5 kg/m2;
  4. 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.

  5. 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.

Exclusion Criteria:

  1. Being doubtful about their availability to complete the trial.
  2. 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).
  3. Previous history of cancer, except for adequately treated basal cell or squamous cell carcinoma of the skin.
  4. Active or latent Tuberculosis or who have a history of Tuberculosis
  5. History of invasive systemic fungal infections or other opportunistic infections
  6. Systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process
  7. Serious infection associated with hospitalisation and/or which required intravenous antibiotics
  8. History of and/or current cardiac disease
  9. 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
  10. Intake medication with a half-life > 24 h within 4 weeks or 5 half-lives of the medication prior to investigational product administration
  11. Have a history of smoking >10 cigarettes per day.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CinnaGen adalimumab
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
A single 40-mg dose of Adalimumab is administered subcutaneously to all the subjects.
Other Names:
  • Humira
  • CinnoRA
Active Comparator: AbbVie adalimumab
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
A single 40-mg dose of Adalimumab is administered subcutaneously to all the subjects.
Other Names:
  • Humira
  • CinnoRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the concentration-time curve from time zero to infinity (AUCinf)
Time Frame: 71 days
AUCinf will be calculated using the equation:AUCinf= AUClast + (Clast / Kel)
71 days
Maximum serum concentration (Cmax)
Time Frame: 71 days
It is obtained directly from the observed concentration-time data
71 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast)
Time Frame: 71 days
It is calculated using the linear trapezoidal rule
71 days
Time to Cmax (Tmax)
Time Frame: 71 days
It is obtained directly from the observed concentration-time data
71 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cinnagen

Investigators

  • Study Director: Somayeh Amini, PharmD, Orchid Pharmed Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 22, 2016

Primary Completion (Actual)

August 6, 2017

Study Completion (Actual)

August 6, 2017

Study Registration Dates

First Submitted

September 3, 2017

First Submitted That Met QC Criteria

September 3, 2017

First Posted (Actual)

September 6, 2017

Study Record Updates

Last Update Posted (Actual)

September 19, 2018

Last Update Submitted That Met QC Criteria

September 18, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ADA.CIN.AJ.95 (I-PK)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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