A Study of Certolizumab Pegol to Evaluate Pharmacokinetics and Safety in Adult Healthy Chinese Subjects

NCT02365948 | Completed Phase 1

• 1 other identifier: RA0045
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study will characterize the pharmacokinetics (PK) of certolizumab pegol (CZP) and evaluate safety of CZP in healthy Chinese subjects. 36 subjects will be randomized to receive one of 3 dose levels of CZP or placebo. The total study duration will be approximately 71-94 days for each subject.

Conditions

Healthy Subjects

Keywords

Pharmacokinetics; Certolizumab Pegol; Healthy Chinese subjects

Outcome Measures

Primary Outcomes (2)

• The area under the plasma concentration-time curve from time zero up to the last analytically quantifiable concentration (AUC 0-t)

  AUC 0-t is within a period of 70 days following the dose of CZP, reported in units of μg/mL·h, as determined using the linear trapezoidal rule.

  D1 (pre-dose and 1, 2, 4, 8, 12 hrs post-dose), D2 (24, 36 hrs post-dose), D3 (48 hrs post-dose), D4 (72 hrs post-dose), D5 (96 hrs post-dose), D6, D8, D15, D22, D29, D43, D57 and D70

• Maximum plasma concentration (Cmax)

  The maximum observed plasma concentration of CZP.

  D1 (pre-dose and 1, 2, 4, 8, 12 hrs post-dose), D2 (24, 36 hrs post-dose), D3 (48 hrs post-dose), D4 (72 hrs post-dose), D5 (96 hrs post-dose), D6, D8, D15, D22, D29, D43, D57 and D70

Secondary Outcomes (3)

• Area under the plasma concentration-time curve from zero up to infinity (AUC)

  D1 (pre-dose and 1, 2, 4, 8, 12 hrs post-dose), D2 (24, 36 hrs post-dose), D3 (48 hrs post-dose), D4 (72 hrs post-dose), D5 (96 hrs post-dose), D6, D8, D15, D22, D29, D43, D57 and D70

• Time to reach a maximum plasma concentration (Tmax)

  D1 (pre-dose and 1, 2, 4, 8, 12 hrs post-dose), D2 (24, 36 hrs post-dose), D3 (48 hrs post-dose), D4 (72 hrs post-dose), D5 (96 hrs post-dose), D6, D8, D15, D22, D29, D43, D57 and D70

• Terminal half-life (t½)

  D1 (pre-dose and 1, 2, 4, 8, 12 hrs post-dose), D2 (24, 36 hrs post-dose), D3 (48 hrs post-dose), D4 (72 hrs post-dose), D5 (96 hrs post-dose), D6, D8, D15, D22, D29, D43, D57 and D70

Study Arms (4)

Certolizumab Pegol 100 mg

EXPERIMENTAL

Subjects will receive100 mg of CZP given by subcutaneous injections in healthy Chinese subjects. The dose group begins treatment on Day 1. To achieve an injectable CZP 100 mg dose, a manual process will be applied by the unblinded site pharmacist.

Biological: Certolizumab Pegol; Other: Placebo

Certolizumab Pegol 200 mg

EXPERIMENTAL

Subjects will receive 200 mg of CZP given by subcutaneous injections in healthy Chinese subjects. The dose group begins treatment staggered by a minimum of 14 days from CZP 100 mg. Dose escalation will be suspended according to the predefined criteria and process.

Biological: Certolizumab Pegol; Other: Placebo

Certolizumab Pegol 400 mg

EXPERIMENTAL

Subjects will receive 400 mg of CZP (two injections of CZP 200 mg) given by subcutaneous injections in healthy Chinese subjects. The dose group begins treatment staggered by a minimum of 14 days from CZP 200 mg. Dose escalation will be suspended according to the predefined criteria and process.

Biological: Certolizumab Pegol; Other: Placebo

Placebo

PLACEBO COMPARATOR

For assessment of the Adverse Event (AE) profile, there are 2 placebo controls in each dose group. The placebo subjects receive the injection of saline (NaCl 0.9 %) at the same time (and of the same volume) as the CZP subjects.

Other: Placebo

Interventions

Certolizumab Pegol BIOLOGICAL

* Active Substance: Certolizumab Pegol * Pharmaceutical Form: Prefilled syringes * Concentration: 200 mg/mL * Route of Administration: Subcutaneous injection

Also known as: Cimzia, CDP870, CZP

Certolizumab Pegol 100 mg; Certolizumab Pegol 200 mg; Certolizumab Pegol 400 mg

Placebo OTHER

* Active Substance: Placebo * Pharmaceutical Form: Prefilled syringes * Concentration: 0.9 % Saline * Route of Administration: Subcutaneous injection

Also known as: PBO

Certolizumab Pegol 100 mg; Certolizumab Pegol 200 mg; Certolizumab Pegol 400 mg; Placebo

Eligibility Criteria

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

You may qualify if:

• An Institutional Review Board (IRB) / Independent Ethics Committee (IEC) approved written Informed Consent Form (ICF) is signed and dated by the subject
• Subject is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule or medication intake according to the judgment of the investigator
• Subject is male or female between 18 and 45 years of age, inclusive
• Results of clinical laboratory tests within the reference range of the laboratory or outside the reference range of the laboratory but considered as nonclinically significant by the investigator. This is not allowed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin values above the upper limit of normal (ULN) ranges
• Have a body weight of 50 to 80 kg and a body mass index (BMI) between 19 and 24 kg/m\^2
• In good health as determined by the investigator on the basis of medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG) and results of laboratory tests during the Pretreatment Period (Screening and Baseline)
• Nonsmoker and former smoker who have given up smoking more than 6 months before first administration
• Willing to abstain from alcohol-, tobacco- and caffeine-containing products for 48 hours prior to admission into the clinic and during the entire in-clinic stay
• Subjects should be a registered permanent Citizen of the People's Republic of China and are Chinese as evidenced by all 4 grandparents as Chinese by ethnical definition
• Female subjects of childbearing potential should have negative pregnancy test at Screening and at Baseline (Day -1) and should use a medically accepted method of contraception (one barrier method and including another - ie, hormonal contraception for at least 2 cycles, intrauterine device, implant device, diaphragm with spermicide, monogamous relationship with vasectomized \[for at least 3 months\] partner or using condoms with spermicide gel) during the entire duration of the study

You may not qualify if:

• Active malignancies or a history of malignancy, excluding basal cell carcinoma of the skin that had been excised prior to study start
• History of adverse reaction to polyethylene glycol
• History of severe or multiple allergies
• Known Tuberculosis (TB) disease, high risk of acquiring TB infection, or latent TB infection
• A history of chronic infection, recent serious or life-threatening infection (within 6 months, including herpes zoster), or a current sign or symptom that may indicated an infection
• Subject with a history or active systemic / respiratory infection due to fungal, parasitic, or mycotic pathogens including but not limited to histoplasmosis, coccidiosis, paracoccidiosis, pneumocystis, blastomyces, aspergillus, and nontuberculous mycobacteria
• History of an infected joint prosthesis at any time with prosthesis still in situ
• Positive hepatitis B surface antigen, hepatitis C Virus immunoglobulin G (HCV IgG), or Human Immunodeficiency Virus (HIV) test result during the Screening
• Subject with blood pressure and pulse rate (measured in supine position, after 10 minutes rest) outside the normal range
• A mean corrected QT interval using Bazett's formula (QTcB) interval \>450 ms at Screening. If the mean QTcB exceeds the limits above, one additional triplicate electrocardiogram (ECG) may be taken. If this triplicate also gives an abnormal result, the subject should be excluded
• Any history or evidence of any clinically significant (CS) cardiovascular, gastrointestinal, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy, or any other CS abnormality, as judged by the investigator
• History of substance abuse, drug addiction or alcoholism within 3 years prior to Screening
• Inability to abstain from smoking during the in-clinic stay
• Subject has made a blood donation or had a comparable blood loss (\>350 mL) within the last 3 months prior to first intake of study drug
• Positive result of alcohol test or urine drug Screen

Sponsors & Collaborators

• UCB Pharma SA: lead
• Parexel: collaborator

Study Sites (1)

1

Shanghai, China

Location

MeSH Terms

Interventions

Certolizumab Pegol

Intervention Hierarchy (Ancestors)

Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: February 11, 2015
• First Posted: February 19, 2015
• Study Start: March 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 14, 2015

Record last verified: 2015-08

Locations

CN (1)