A Study to Evaluate Pharmacokinetics of DRL_AB in Healthy Male Participants

Official title

A Single-dose, Randomized, Open-label, Parallel-arm, Comparative Pharmacokinetic and Safety Study of Proposed Abatacept Biosimilar DRL_AB Administered by the Subcutaneous Route Via Autoinjector or Prefilled Syringe to Normal, Healthy, Male Participants

Overview

The purpose of this study is to assess the PK comparability and compare safety and tolerability of DRL\_AB administered via an auto injector (AI) or prefilled syringe (PFS) in healthy male participants.

Interventions

• Biological DRL_AB
  DRL\_AB administered as a SC injection.

Primary outcome measures

• Area Under the Serum Concentration Versus Time Curve From Time 0 Extrapolated to Time t (AUC0-t) of DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]
• Maximum Measured Serum Concentration (Cmax) in DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]
• Area Under the Serum Concentration Versus Time Curve From Time 0 Extrapolated to Infinite Time (AUC0-∞) of DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]

Secondary outcome measures (7)

• Time of the Maximum Measured Serum Concentration (Tmax) of DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]
• Apparent Terminal Decline Rate Constant (λz) of DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]
• Terminal Elimination Half-life (t1/2) of DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]
• Apparent Volume of Distribution (Vz/f) of DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]
• Apparent Body Clearance (CL/f) of DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]
• Area Under the Curve Extrapolated as a Percentage of the Total (%AUCextrap) of DRL_AB [Time frame: Pre-dose on Day 1. Post-dose at 1, 4, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 216, 336, 504, 672, 840, 1008, 1176, 1344 and 1680 hours]
• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) [Time frame: From start of study drug administration to end of study (EOS) (Up to Day 71)]

Eligibility criteria

Inclusion criteria

• Healthy male volunteers aged 18 to 50 years (both inclusive) at the time of signing informed consent form.
• Ability and amenability to provide written informed consent to participate in the study and adhere to study requirements.
• Body mass index in the range 18.5-30.0 kilogram per meter square (kg/m\^2) (both inclusive) and body weight of 60.0-100.0 kilogram (kg) (both inclusive).
• General good health as determined by a qualified physician based on a comprehensive medical history, physical examination, vital signs, clinical laboratory tests (hematology, biochemistry, and urinalysis), and 12-lead electrocardiogram (ECG) during screening.
• Vital signs, physical examination, clinical laboratory tests, and 12-lead ECG results within normal range, or if outside the normal range, then assessed as clinically non-significant by the investigator (unless the value constitutes an explicit exclusion criterion).
• Willingness to use or with female partners (women of childbearing potential \[WOCBP\]) willing to use at least one highly effective method of contraception as described below up to at least 3 months from the time of study intervention administration.

Note: Highly effective birth control measures per Clinical Trials Facilitation and Coordination Group (CTCG) guidelines 202414 include the following:

For a male participant:

• Permanently sterile by bilateral orchidectomy
• Vasectomy
• Maintaining sexual abstinence\*.

For the female partner of a male participant:

• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation - oral, intravaginal, injectable, and transdermal.
• Progestogen-only hormonal contraception associated with inhibition of ovulation - oral, injectable, and implantable.
• Intrauterine device
• Intrauterine hormone-releasing system
• Bilateral tubal occlusion Sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. \[Note: The reliability of sexual abstinence needs to be evaluated as per investigator's judgement in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. It should be considered as true abstinence only; and not periodic abstinence (such as calendar, symptothermal, post-ovulation methods)\].
• Willingness to abide by study restrictions for the entire study duration.

Exclusion criteria

• Positive or 2 successive indeterminate test results for Quantiferon-tuberculosis (TB) Gold test.
• Positive results for syphilis, hepatitis B (HBsAg, HBsAb, HBcAb), hepatitis C, or human immunodeficiency virus (HIV)-1 or 2.
• Any prior exposure to abatacept or any other agent directly acting on CTLA4 or the CD28-CD80 co-stimulation pathway \[e.g., pembrolizumab, ipilimumab, nivolumab, and atezolizumab\] including investigational products.
• Vaccination with live vaccines within 3 months prior to screening or intention to receive live vaccines during the trial or up to 3 months after the administration of the study intervention. Participants who have been administered non-live vaccines at least more than a week prior to study intervention administration may be included.
• History of immunodeficiency or other clinically significant immunological disorders, autoimmune disorders, or ongoing or frequent/recurring infections defined as >3 infections per year requiring treatment, participants with prior herpes zoster infection not fully healed (including the post-herpetic neuralgia period if present) within one year prior to randomization, or participants with history of systemic fungal infection within the 6 months prior to screening.
• Allergy or hypersensitivity to any recombinant human or humanized antibodies, other therapeutic proteins or any excipients (dibasic sodium phosphate anhydrous, monobasic sodium phosphate monohydrate, L-histidine, sodium chloride, poloxamer and sucrose) of the study interventions.
• History and/or current manifestations of clinically significant (in the opinion of the investigator) atopic allergy (e.g., asthma including childhood asthma currently showing clinical manifestations, urticaria, angioedema, eczematous dermatitis), hypersensitivity, or allergic reactions or any history or presence of vasculitis or psoriasis.
• Skin not suitable for dosing or post-dosing evaluations on the upper arm for any reasons (including presence of tattoos, skin pigmentation disorders, scarring etc., which may obscure the injection site).
• Participation in blood donation or in any study requiring repeated blood sampling, hemorrhage requiring treatment, any transfusion in the past 3 months, or plasma donation within the 14 days prior to screening.
• Systolic blood pressure >140 millimeter of mercury (mm Hg) or diastolic blood pressure >90 mm Hg when measured in the sitting position after 5 minutes rest, or current use of antihypertensive drugs. Participants may be enrolled if blood pressure measurement is repeated up to 2 times on same or different days and if the mean of the measurements is within the above limits.
• History of relevant orthostatic hypotension, fainting spells, or blackouts as well as history of difficulties with blood sampling that may potentially interfere with the study objectives and be deemed in the opinion of the investigator to pose clinical risk to the participants.
• QTc (Fridericia correction) longer than 450 milliseconds or other clinically relevant ECG abnormalities such as atrial fibrillation, atrial flutter, Wolf-Parkinson-White syndrome, or presence of a cardiac pacemaker as found relevant clinically by the investigator.
• History or presence of any clinically relevant nervous system disease including, but not restricted to stroke, transient ischemic attack, or seizures other than febrile seizures before the age of 5 years.
• History of and/or current gastrointestinal, renal, endocrine, pulmonary, hepatic, cardiovascular (including history of or presence of angina, exertional dyspnea, orthopnea, congestive heart failure or myocardial infarction and thrombotic or embolic episode requiring treatment), hematological (including pancytopenia, aplastic anemia or blood dyscrasia and coagulopathies, or an international normalized ratio (INR) >1.5), or metabolic disorders (including known diabetes mellitus) considered significant by the investigator. This criterion includes any disorder or condition that in the investigator's opinion may interfere with the safety of the participant, the study evaluations, or the participant's compliance to the study procedures and limitations.
• Impaired hepatic function (alanine transaminase \[ALT\] or aspartate transaminase \[AST\] level >1.5× times upper limit of normal \[ULN\] and/or serum total bilirubin 1.5× ULN at screening). A single repeat test on a different day is allowed. Participants with documented evidence of presence of Gilbert's disease may be included if total bilirubin is 80% of the total bilirubin as per laboratory test.
• Participants with HbA1c >= 6.5%, indicative of diabetes mellitus
• Presence of any active infection assessed by the investigator even if minor and ongoing at the time of screening or on check-in day or presence of any non-healed wound or bone fracture of a clinically relevant size in the investigator's opinion.
• Participation in an interventional or phase 1 study in the last 3 months before enrollment, participation in more than 3 studies on experimental drug products in the past 12 months, intake of an investigational drug in a clinical trial setting within 3 months or 5 half-lives (whichever is longer) prior to intake of study drug in this trial, planned intake of an investigational drug with follow up visit scheduled during the course of this trial, or intake for any reason in the last 6 months of some specific long-body residence drugs such as any immunoglobulin or antibody.
• History of any cancer, including carcinoma in situ, lymphoma, or leukemia.
• Major surgery within the past 6 months or any surgery including dental interventions within 3 months before study enrollment.
• Intake of any medication including herbal products, vaccines, or immunomodulators within 3 weeks prior to study intervention administration other than nonsteroidal anti-inflammatory drugs (NSAIDs). If any other drugs have been used, there should not be any evidence of potential drug-drug interaction with abatacept.
• Current smokers or those who have given up smoking including use of alternative tobacco products such as chewing tobacco and vaping <=2 weeks prior to screening, or participants with positive urine cotinine test at screening or check-in.
• Positive alcohol breath test or positive urine test for drugs of abuse (including benzodiazepines, amphetamines, barbiturates, cocaine, methadone, phencyclidine, 3,4-methylenedioxymethamphetamine, tetrahydrocannabinol, and opiates) at screening or at check-in.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

New Zealand · 3 centers

• Momentum Clinical Research — Auckland
• New Zealand Clinical Research — Auckland
• New Zealand Clinical Research — Christchurch

Identifiers

NCT: NCT07744828 · AB-01-010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗