Clinical trial NCT05863442: Comparative PK, Safety, Tolerability, Immunogenicity, and PD Profile Study of TUR03 and Soliris in Healthy Participants
Official title: A First-in-human, Randomized, Double-blind, Parallel-group Study to Evaluate the PK, Safety, Tolerability, Immunogenicity, and PD Profile of a Single Intravenous Dose of TUR03 Compared With Soliris® in Healthy Adult Male Participants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy
Keywords: eculizumab
phase I
biosimilar
Lead sponsor: Turgut Ardika PTY LTD
Sponsor class: INDUSTRY
First posted: 2023-05-18
Enrollment: 120
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study is designed as a randomized, double-blind, parallel-group study to evaluate the PK, safety, tolerability, immunogenicity, and PD of TUR03 compared to Soliris, when administered as a single IV infusion in healthy adult male participants.


Eligibility criteria: Inclusion Criteria:

Participants are eligible to be included in the study only if ALL of the following criteria apply:

1. Capable of giving signed informed consent as described in Section 10.1, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol.
2. Participants assigned male at birth who are ≥18 years and ≤45 years old at the time of signing the ICF.
3. Body weight ≥50 kg and ≤90 kg and body mass index (BMI) ≥18.00 kg/m2 and ≤30.00 kg/m2 at Screening and Day -1.
4. Participants must be healthy as determined by the Investigator, based on medical history, physical examination, vital signs, ECG, and clinical laboratory evaluations at Screening and Day -1, as follows:

   1. Hematology and coagulation results within reference ranges.
   2. Liver function panel analyte values ≤1.5 × upper limits of normal (ULN), which include aspartate transaminase, alanine transaminase, and total bilirubin (for participants with Gilbert's Syndrome, total bilirubin ≤3.0 × ULN is allowed if direct bilirubin is ≤50%), alkaline phosphatase, and gamma glutamyl transferase at Screening.
   3. Urinalysis within reference ranges or showing no clinically significant findings.

   NOTE: One repeat of clinical laboratory tests is allowed at the discretion of the Investigator.
5. Participants must have documented evidence of prior complete vaccination with meningococcal vaccines against N. meningitidis serogroup B at any time and against serogroups A, C, W, and Y within 5 years prior to Screening in line with local immunization requirements or must agree to be vaccinated against N. meningitidis during the study.
6. Nonsterilized participants with partners of childbearing potential must agree to take appropriate contraceptive measures (as described in Section 10.4) from Day 1 until 5 months after IP administration and refrain from donating sperm during this period. NOTE: Participants with pregnant partners are excluded.
7. Nonsmoker or occasional smoker, ie, smokes ≤10 cigarettes (or equivalent of tobacco- or nicotine-containing products) per week within 30 days prior to Screening and is able to abide by the smoking policy of the study site.
8. Ability and willingness to abstain from alcohol from 48 hours before admission to the study site on Day -1, during in-house observation at the study site until discharge, and for 24 hours prior to ambulatory visits.

Exclusion Criteria:

Participants are excluded from the study if ANY of the following criteria apply:

1. Known or suspected hereditary or acquired complement deficiency.
2. History of meningococcal infection.
3. History or evidence of a clinically significant disorder (including psychiatric disorders), condition, or disease that, in the opinion of the Investigator and Medical Monitor or designee, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion. EXCEPTION: Fully resolved childhood asthma is not exclusionary.
4. History of splenectomy.
5. History of surgery or major trauma within 12 weeks of Screening, or surgery planned during the study.
6. A recent history (within 1 week prior to IP administration) or presence or suspicion of current active systemic or local infection, a known risk for developing sepsis, and/or known active inflammatory condition, in the opinion of the Investigator.
7. History of or current invasive malignancy (excluding basal or squamous cell carcinoma that has been fully resected with no evidence of metastatic disease for 1 year).
8. History of ongoing seborrheic dermatitis or eczema.
9. History of clinically significant headaches that, in the opinion of the Investigator, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
10. History of recurrent/chronic hemorrhages or any hemorrhage within 30 days prior to IP administration.
11. History of a drug- or food-induced severe hypersensitivity reaction (eg, immunologic or nonimmunologic anaphylaxis).
12. Known hypersensitivity reaction to penicillin and/or cephalosporin that, in the opinion of the Investigator, would pose a risk to participant safety.
13. Known hypersensitivity to any component of TUR03 or Soliris, murine proteins, or other monoclonal antibodies.
14. Known hypersensitivity to any component of meningococcal vaccines, including those containing diphtheria toxoid, or a life-threatening reaction after previous administration of a vaccine containing similar components.
15. Hypertension at Screening or Day -1 (defined as a systolic blood pressure \[BP\] \>140 mm Hg and/or a diastolic BP \>90 mm Hg, confirmed by a single repeat measurement that same day) or a history of hypertension requiring pharmacological intervention.
16. Proteinuria at Screening or Day -1 (with a urine dipstick value of 1+ or above)..
17. Tests positive for human immunodeficiency virus (HIV 1 and 2), hepatitis B virus surface antigen, hepatitis B core antibody, or hepatitis C virus.
18. Tests positive for tuberculosis (TB) using the QuantiFERON®-TB Gold test at Screening or, if indeterminant result on the first test, tests positive or indeterminant on repeat QuantiFERON-TB Gold test.
19. Positive screen for alcohol by breath test and/or potential drugs of abuse by urine drug screen at Screening or Day -1. NOTE: One repeat screen is allowed at the discretion of the Investigator.
20. History of alcohol or drug abuse or drug addiction (including cannabis products) within the last 12 months prior to Screening.
21. Prior exposure to eculizumab or similar compounds (ie, a monoclonal antibody that specifically binds to the complement protein C5).
22. Use of immunoglobulins or iron supplementation within 3 months prior to Screening.
23. Use of any over-the-counter (OTC) medications, herbal remedies such as St. John's Wort extract, or prescription medications within 7 days or 5 half lives (whichever is longer) prior to IP administration. EXCEPTIONS: Vitamins, dietary supplements, and paracetamol (up to 4 g per day, but \<1 g in 4 hours) for analgesia are not exclusionary.
24. Use of other investigational drugs (or is currently using an investigational device) within 60 days or 5 half-lives (whichever is longer) prior to IP administration.
25. Vaccination with a live vaccine within 30 days prior to IP administration, or vaccination with an inactivated vaccine or approved COVID-19 vaccine within 14 days prior to IP administration, or planning to get vaccinated during the study period. EXCEPTIONS: Receipt of required meningococcal vaccinations per protocol is not exclusionary.
26. Veins unsuitable for venous blood collection.
27. Donated blood (including blood products) or experienced loss of blood ≥500 mL within 30 days of Screening, or donated plasma within 7 days of Screening.
28. Participant is a family member or employee of the Investigator or Sponsor.

Primary outcomes:
measure: PK similarity of TUR03 and Soliris following a single IV infusion in healthy participants
timeFrame: Day 1 - Day 57
Secondary outcomes:
measure: Eculizumab serum concentration-time profile
timeFrame: Day 1 - Day 57
measure: Maximum serum concentration (Cmax)
timeFrame: Day 1- Day 57
measure: Area under the concentration-time curve from time zero to the last quantifiable concentration (AUClast)
timeFrame: Day 1- Day 57
measure: Time to Cmax
timeFrame: Day 1 - Day 57
measure: Terminal half-life
timeFrame: Day 1 - Day 57
measure: Volume of distribution during terminal phase after intravenous administration
timeFrame: Day 1 - Day 57
measure: Terminal elimination rate constant
timeFrame: Day 1 - Day 57
measure: Total serum clearance of drug after intravenous administration
timeFrame: Day 1 - Day 57
measure: AEs and AESI
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Hematology
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Coagulation - International normalized ratio
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Coagulation - Activated partial thromboplastin time
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Coagulation - Prothrombin time
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Urea
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Carbon dioxide (bicarbonate)
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Creatinine
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - AST
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - ALT
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - ALP
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Glucose (fasting)
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Gamma glutamyl transferase
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Total Protein
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Creatine kinase
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Potassium
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Lactate dehydrogenase
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Sodium
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Albumin
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Chloride
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Total and direct bilirubin
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Calcium
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Triglycerides
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Phosphate
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Clinical chemistry - Cholesterol
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Leukocytes
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Red blood cells
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Protein
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - pH
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Bilirubin
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Nitrite
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Urobilinogen
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Specific gravity
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Ketones
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Glucose
timeFrame: Day 1 - Day 57
measure: Incidence of Treatment-Emergent changes in safety clinical laboratory parameters from baseline and Grade 3 laboratory abnormalities - Urinanalysis - Microscopy
timeFrame: Day 1 - Day 57
measure: Changes in vital signs - Blood Pressure
timeFrame: Day 1 - Day 57
measure: Changes in vital signs - Pulse rate
timeFrame: Day 1 - Day 57
measure: Changes in vital signs - Body Temperature
timeFrame: Day 1 - Day 57
measure: Changes in Electrocardiograms (ECG) - Heart rate
timeFrame: Day 1 - Day 57
measure: Changes in Electrocardiograms (ECG) - PR interval
timeFrame: Day 1 - Day 57
measure: Changes in Electrocardiograms (ECG) - RR interval
timeFrame: Day 1 - Day 57
measure: Changes in Electrocardiograms (ECG) - QRS duration
timeFrame: Day 1 - Day 57
measure: Changes in Electrocardiograms (ECG) - QT interval
timeFrame: Day 1 - Day 57
measure: Number of patients with treatment-related adverse events as assessed by CTCAE v4.0 via physical examination
timeFrame: Day 1 - Day 57
measure: Comparison of the immunogenicity of TUR03 and Soliris following a single IV infusion in healthy participants - Frequency of antidrug antibodies (ADAs)
timeFrame: Day 1 - Day 57
measure: Comparison of the immunogenicity of TUR03 and Soliris following a single IV infusion in healthy participants - Antidrug antibody titers
timeFrame: Day 1 - Day 57
measure: Comparison of the immunogenicity of TUR03 and Soliris following a single IV infusion in healthy participants - Neutralizing antibodies (NAbs)
timeFrame: Day 1 - Day 57
measure: PD profile of TUR03 and Soliris - ABEC (0-1344) CH50
timeFrame: Day 1 - Day 57
measure: PD profile of TUR03 and Soliris - AUEC(0-1344) CH50
timeFrame: Day 1 - Day 57
measure: PD profile of TUR03 and Soliris - Emin CH50
timeFrame: Day 1 - Day 57
measure: PD profile of TUR03 and Soliris - Tmin CH50
timeFrame: Day 1 - Day 57
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Q-Pharm Pty Limited
state: Queensland
Study officials:
References: