Phase I, Pharmacokinetic, Safety and Tolerability Study in Healthy Volunteers

NCT03522012 | Completed Phase 1 FDA Drug

• 1 other identifier: LusiNEX-HV-PK-001
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, 3-arm, parallel-group single-dose study to compare the PK, PD, safety, tolerability, and immunogenicity of LusiNEX (Mycenax tocilizumab) versus RoActemra (EU tocilizumab) and Actemra (US tocilizumab) after a single IV infusion of 4 mg/kg in healthy volunteers (hereafter referred to as subjects). The therapeutic dose of tocilizumab starts with 4 mg/kg and ranges to 12 mg/kg, considering 4 mg/kg is the lowest dose, the same has been selected for the study.

Conditions

Pharmacokinetics

Keywords

Pharmacokinetics; Tocilizumab

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics

  Area under concentration-time curve from time 0 (predose) extrapolated to infinity (AUC(0-∞)).

  2 months

Secondary Outcomes (10)

• Cmax

  2 months

• tmax

  2 months

• AUC(0-t)

  2 months

• t1/2

  2 months

• Vss

  2 months

Study Arms (3)

LusiNex

EXPERIMENTAL

4 mg/kg, single-dose IV infusion (Mycenax tocilizumab)

Drug: Tocilizumab

RoActemra

ACTIVE COMPARATOR

4 mg/kg, single-dose IV infusion (RoActemra; tocilizumab marketed in EU )

Drug: Tocilizumab

Actemra

ACTIVE COMPARATOR

4 mg/kg, single-dose IV infusion (Actemra; tocilizumab marketed in US)

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Tocilizumab is a recombinant human monoclonal antibody of the immunoglobulin G1 subclass, directed against the IL-6 ligand specific receptor. By preventing the binding of IL-6 to its receptor, tocilizumab inhibits the biological activity of IL-6. Tocilizumab was approved by the US Food and Drug Administration (4 mg/kg with an increase to 8 mg/kg based upon clinical response) for the treatment of adult patients with moderate to severe active rheumatoid arthritis, who have had inadequate response to one or more tissue necrotizing factor (TNF) antagonist therapies. Tocilizumab is currently approved in 95 countries for the treatment of adult onset moderate to severe rheumatoid arthritis.

Also known as: ACTEMRA

Actemra; LusiNex; RoActemra

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing to provide written informed consent prior to performing study-related procedures.
• Healthy male or female aged between 18 to 55 years, inclusive.
• A body mass index between 18 to 30 kg/m2, inclusive.
• Medically healthy with clinically insignificant results (e.g., medical history, electrocardiograms \[ECGs\], and physical examination) as judged by the Principal Investigator at Screening/Day 1 (admission to study center).
• All laboratory results including, but not restricted to, complete blood counts, liver function, and lipid profile should be within the normal range or clinically insignificant as judged by the Investigator at Screening/Day 1 (admission to study center). An abnormal laboratory result considered to be erroneous, may be repeated once during Screening at the discretion of the Investigator.
• Have systolic blood pressure ≤140 and ≥90 mmHg, diastolic blood pressure ≤90 and ≥50 mmHg, and a heart rate ≥40 and ≤100 beats per minute at Screening/Day 1 (admission to study center).
• Has to agree to abstain from alcohol intake 48 hours before administration of the study drug and during the inpatient period of the study.
• Negative urine drug screen/alcohol breathylzer test at Screening/Day 1 (admission to study center).
• Non-smokers or social smokers (defined as less than 10 cigarettes per week). No current use of any nicotine containing product. Cotinine levels ≤5 ng/mL.
• Willing to abstain from sexual intercourse or use 2 methods of contraception (both male and female partners) as defined in the protocol for 3 months after study drug administration.
• Female subjects who are using oral hormonal contraceptives must be willing to use, with their partner, 2 methods of contraception as defined as defined in the protocol.
• Has to agree to not donate sperm or ova for at least 3 months after study drug administration.
• Subjects who are negative for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibodies, human immunodeficiency virus I and II, as well as tuberculosis (TB) tests at Screening.
• Did not receive a blood transfusion within 4 weeks prior to study drug administration, donate 400 mL or more blood within 8 weeks prior to study drug administration or donate plasma within 4 weeks prior to study drug administration and agrees to not make blood donations, including red blood cells, plasma, platelets, or whole blood for the duration of the study and for 3 months after study drug administration.
• Able to be compliant with the protocol and attend all scheduled visits.

You may not qualify if:

• Volunteers with any known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections.
• Have been treated with IV antibiotics for an infection within 8 weeks or oral antibiotics within 2 weeks prior to Screening.
• History of TB infection, active TB or latent TB infection, or recent exposure to a person with active TB.
• Previous exposure to therapeutic monoclonal antibodies in the past 6 months prior to Screening.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• A history of clinically significant gastrointestinal, renal, hepatic, cardiovascular, or allergic disease.
• Evidence of active malignant disease, malignancies diagnosed within the previous 2 years (except basal cell carcinoma of the skin that has been excised and cured), or breast cancer diagnosed within the previous 2 years.
• Impaired liver function as determined by:
• Serum alanine aminotransferase and/or aspartate aminotransferase \>1.5 x upper limit of normal (ULN) at Screening or admission to the study center. Subjects with values between ULN and 1.5 x ULN may be included in the study if considered not clinically significant by the Investigator.
• Current or past history of diverticulitis or biliary obstruction.
• Presence of proteinuria (other than trace amounts i.e., +, ++/+++) at Screening or admission to the study center.
• Administration of an investigational product in another study within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to screening, or are currently participating in another clinical study of an investigational drug, or intending to participate in another clinical study of an investigational drug before completion of all scheduled evaluations in this clinical study.
• Use of any prescription or over-the-counter medication (with the exception of contraceptive medication in females and paracetamol) within 7 days of Screening and for the duration of participation in the study. This includes the use of any NSAIDs (including aspirin) within 28 days before study drug administration and for the duration of participation in the study.
• Intake of herbal drugs or dietary supplements excluding routine vitamins but including megadose (intake of 20 to 600 times the recommended daily dose) vitamin therapy within 28 days prior to study drug administration, unless agreed as not clinically relevant by the Investigator and Sponsor.
• Regular alcohol consumption of \>14 (female subjects) or \>21 (male subjects) units of alcohol per week at the time of Screening (1 unit = 150 mL of wine or 360 mL of beer or 45 mL of 40% alcohol).

Sponsors & Collaborators

• Mycenax Biotech Inc.: lead

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Interventions

tocilizumab

Study Officials

• Oscar Walsh, Dr.

  Nucleus Network Ltd

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: May 11, 2018
• Study Start: October 17, 2017
• Primary Completion: September 26, 2018
• Study Completion: December 20, 2018
• Last Updated: February 26, 2019

Record last verified: 2018-11

Locations

AU (1)