Clinical trial NCT04295356: To Compare the Pharmacokinetics and Safety of the Auto-injector and Pre-filled Syringe of CT-P17
Official title: A Phase 1, Randomized, Open-label, Two-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics and Safety of the Auto-injector and Pre-filled Syringe of CT-P17 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Celltrion
Sponsor class: INDUSTRY
First posted: 2020-03-04
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was phase 1, randomized, open-label, two-arm, parallel group, single-dose study, which was designed to compare the pharmacokinetics (PK) and safety of CT-P17 SC administration via AI and PFS in healthy subjects. Approximately 180 subjects were enraollend and randomly assigned to one of the two treatment arms in a 1:1 ratio. In each treatment arm, all subjects received a single dose (40 mg) of CT-P17 via either AI or PFS on Day 1 followed by 10 weeks during which PK, safety, and immunogenicity measurements were made. The randomization to treatment assignment was stratified by body weight (≥80 kg vs. \<80 kg) as measured on baseline (Day -1), gender (male vs. female) and study center.


Eligibility criteria: Inclusion Criteria:

Subjects who meet all of the following criteria will be considered eligible to participate in the clinical study:

1. Healthy male or female subjects, between the ages of 18 and 55 years, both inclusive (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and heart rate measurement, 12-lead electrocardiogram \[ECG\], and clinical laboratory tests prior to the administration of the study drug).
2. Subject with C-reactive protein ≤1.5 times the upper limit of normal (ULN).
3. Subject has adequate liver function as determined by following results:

   * Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 times ULN and
   * Total bilirubin ≤1.5 times ULN.
4. Subject is informed and able to understand the full nature and purpose of the study, including possible risks and side effects, and is given ample time and opportunity to read and understand this information. The subject has the ability and agrees to cooperate with the investigator and must sign and date the written informed consent prior to performing any of the screening procedures.
5. BMI between 18.0 and 29.9 kg/m2, both inclusive, when rounded to the nearest tenth.
6. Subject and their partner of childbearing potential must agree to use highly effective method of contraception as specified in Section 5.8.2 throughout the study and for 5 months after the administration of the study drug. A man or woman is of childbearing potential if, in the opinion of the investigator, he or she is biologically capable of having children and is sexually active. Male and female subjects and their partners who have been surgically sterilized for less than 24 weeks prior to the date of informed consent must agree to use any medically acceptable methods of contraception. Menopausal females must have experienced their last period more than 1 year prior to the date of informed consent to be classified as not of childbearing potential.

Exclusion Criteria:

Subjects who meet any of the following criteria will not be considered eligible to participate in the clinical study:

1. Subject has a medical history and/or condition including one or more of the following disease(s):

   * History and/or current presence of clinically significant atopy (e.g., allergic asthma, eczematous dermatitis), known or suspected clinically relevant hypersensitivity or allergic reactions to any of the excipients of study drug, other murine and human proteins or immunoglobulin products.
   * History of infection with hepatitis B (active or carrier of hepatitis B), hepatitis C, human immunodeficiency virus (HIV) or syphilis. However, a subject with history of hepatitis B virus is allowed if resolved. Subject will be enrolled based on hepatitis B infection eligibility criteria, specified in Section 6.2.3.
   * History of invasive systemic fungal infections (including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis, etc.) or other opportunistic infections judged by the investigator, including local fungal infections or a history of herpes zoster.
   * History of and/or current cardiac (including New York Heart Association class III/IV heart failure), gastrointestinal, renal, endocrine, neurologic, autoimmune, hepatic, hematological (including pancytopenia, aplastic anemia or blood dyscrasia, etc.), metabolic (including diabetes mellitus), or pulmonary disease classed as significant by the investigator.
   * History of any malignancy.
   * History of systemic or local infection, a known risk for developing sepsis, and/or known active inflammatory process or evidence of an infection requiring in-patient hospitalization or intravenous antibiotics within 24 weeks prior to the administration of the study drug (Day 1).
2. Subject is considered to have a significant abnormal cardiac function in investigator's discretion determined by the laboratory results.
3. Subject underwent surgical intervention or an operation within 4 weeks prior to the administration of the study drug (Day 1) or plans to have a surgical procedure during the study period.
4. Subject has active tuberculosis (TB), latent TB (defined as a positive result for interferon-γ release assay \[IGRA\] with no active lesion in examination of chest X-ray without any sign or symptom of TB), a history of TB, had close contact with a person with active TB or traveled to areas within a high incidence of TB within 8 weeks prior to the administration of the study drug (Day 1) or has plans to travel to the area in which TB is prevalent during the study period. If the result of IGRA is indeterminate at Screening, retest will be allowed only once during the Screening period. If the repeated IGRA result is again indeterminate or positive, the subject will be excluded from the study. If the repeated IGRA result is negative, the subject may be included in the study.
5. Female subject is pregnant or lactating or planning to be pregnant or to breastfeed before, during, or within 5 months after the administration of the study drug (Day 1).
6. Male subject is planning to father a child or donate sperm within 5 months after the administration of the study drug (Day 1).
7. Subject has received tumor necrosis factor-α blockers, or subject who has had exposure of a biologic agent (including but not limited to monoclonal antibodies or fusion protein) within 6 months prior to the administration of the study drug (Day 1).
8. Subject used prescription (excluding hormonal birth control), over-the-counter drugs, dietary supplements, or herbal remedies that could affect the outcome of the study within 2 weeks prior to the administration of the study drug (Day 1).
9. Subject has undergone treatment with an investigational drug or participated in another clinical trial for healthy subject or bioequivalence test within 90 days or 5 half-lives (whichever is longer) prior to the administration of the study drug (Day 1) or plan to do so during the study.
10. Subject received a live or live-attenuated vaccine within 4 weeks prior to the administration of the study drug (Day 1) or plan to do so until the 6 months after Day 1.
11. Subject has donated or lost 450 mL or more of whole blood within 8 weeks, or donated blood components within 4 weeks prior to the administration of the study drug (Day 1).
12. Subject shows reasonable evidence of drug abuse (positive result for drug urine test and/or the opinion of the investigator).
13. Subject has a history or presence of regular consumption exceeding an average weekly intake of \>21 units of alcohol in recent 12 weeks prior to the administration of the study drug (Day 1). One unit is equivalent to a half-pint (285 mL) of beer/lager, one measure (25 mL) of spirits, or one small glass (125 mL) of wine. Subject is unwilling to avoid use of alcohol or alcohol containing foods, medications, or beverages within 24 hours prior to admission (Day -1), and each study visit until completion of the study.
14. Subject has smoked 10 or more cigarettes per day in the recent 12 weeks prior to the administration of the study drug (Day 1) and/or is unable to refrain from smoking up to 24 hours after the administration of the study drug.
15. In the opinion of the investigator, the subject is not eligible for the study participation for any reason (including clinical laboratory results) or shows evidence of a condition (e.g., psychological or emotional problem, any disorder or resultant therapy) that is likely to invalidate an informed consent or limit the ability of the subject to comply with the protocol requirements. Subject is unable to understand the protocol requirements, instructions, study-related restrictions, or the nature, scope, and possible consequences of the clinical study or is unable to give written informed consent or to comply fully with the protocol.
16. Subject is vulnerable (e.g., employees of the study center or any other individuals involved with the conduct of the study, or immediate family members of such individuals, persons kept in prison, or other institutionalized persons by law enforcement).

Primary outcomes:
measure: Peak Plasma Concentration (Cmax)
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
measure: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC0-inf)
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
measure: Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Quantifiable Concentration (AUC0-last))
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
Secondary outcomes:
measure: Time to Maximum Serum Concentration (Tmax)
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
measure: Terminal Elimination Half-life (t1/2)
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
measure: Terminal Elimination Rate Constant (λz)
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
measure: Apparent Total Body Clearance (CL/F)
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
measure: Apparent Volume of Distribution During the Terminal Phase After Non-IV Administration (Vz/F)
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
measure: Percentage of the Area Extrapolated for Calculation of AUC0-inf (%AUCextrap)
timeFrame: Day 1 predose, 6, 12, 24, 48, 72, 96, 108, 120, 132, 144, 168, 192, 336, 504 hours, Days 29, 43, 57, 71 postdose
measure: Summary of Immunogenicity Assay
timeFrame: Day 1 predose, Days 15, 29, 57, 71 postdose
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Development, LP
state: Texas
Study officials:
affiliation: Celltrion
name: Sung Hyun Kim, Dr
role: STUDY_DIRECTOR
References:
citation: Davidson A, Brimhall D, Kay J, Keystone E, Lee SJ, Kim SH, Bae YJ, Choi EJ, Furst DE. Randomised, phase I pharmacokinetic study of adalimumab biosimilar CT-P17 (40 mg/0.4 mL) by autoinjector and prefilled syringe in healthy subjects. Br J Clin Pharmacol. 2021 Nov;87(11):4323-4333. doi: 10.1111/bcp.14850. Epub 2021 May 9.