A Study Of CinnoRA (Adalimumab-CinnaGen) And Adalimumab (Humira) In Healthy Subjects
Condition: Bioequivalence; Phase 1
Study type: Interventional
Phase: Phase 1

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®.
    

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
    

Intervention name(s): Adalimumab
Intervention type(s): Drug
Intervention description(s): A single 40-mg dose of Adalimumab is administered subcutaneously to all the subjects.
Other intervention name(s): CinnoRA; Humira
Intervention MeSH terms: Adalimumab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: healthy subjects; adalimumab; single dose; Phase 1; PK