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Trial registered on ANZCTR


Registration number
ACTRN12619000694112
Ethics application status
Approved
Date submitted
26/04/2019
Date registered
9/05/2019
Date last updated
16/12/2020
Date data sharing statement initially provided
9/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, double-blind, single-dose study to evaluate the pharmacokinetic, safety, tolerability, immunogenicity and pharmacodynamic profile of ISU305 compared to Soliris® (Eculizumab) in Healthy Male Volunteers
Scientific title
A randomised, double-blind, single-dose study to evaluate the pharmacokinetic, safety, tolerability, immunogenicity and pharmacodynamic profile of ISU305 compared to Soliris® (Eculizumab) in Healthy Male Volunteers
Secondary ID [1] 298067 0
ISU305-001
Universal Trial Number (UTN)
U1111-1232-3783
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal nocturnal haemoglobinuria (PNH) 312569 0
Atypical haemolytic uraemic syndrome (aHUS) 312570 0
Condition category
Condition code
Inflammatory and Immune System 311084 311084 0 0
Other inflammatory or immune system disorders
Blood 311252 311252 0 0
Anaemia
Renal and Urogenital 311253 311253 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single intravenous infusion of 300 mg ISU305 will be investigated against a reference product (Soliris).
Intervention code [1] 314302 0
Treatment: Drugs
Comparator / control treatment
A single dose of 300 mg, intravenous infusion of Solaris. The dose will be prepared by the site pharmacist and administered by the clinical team. Accountability records will be clearly maintained by the site.
Control group
Active

Outcomes
Primary outcome [1] 319869 0
The primary endpoint of the study is the evaluation of AUC(0-inf).
Timepoint [1] 319869 0
Sample Number: Day: Timepoint

1 Day 1 Pre-dose (within 30 minutes prior to dosing)
2 Day 1 End of infusion (35 minutes post start of infusion) (±1 minute)
3 Day 1 4 hours post end of infusion (±2 minutes)
4 Day 1 8 hours post end of infusion (±5 minutes)
5 Day 1 12 hours post end of infusion (±5 minutes)
6 Day 2 24 hours post end of infusion (±5 minutes)
7 Day 3 48 hours post end of infusion (±3 hours)
8 Day 5 96 hours post end of infusion (±3 hours)
9 Day 8 168 hours post end of infusion (±3 hours)
10 Day 11 10 days post end of infusion (±3 hours)
11 Day 15 14 days post end of infusion (±3 hours)
12 Day 22 21 days post end of infusion (±24 hours)
13 Day 29 28 days post end of infusion (±24 hours)
14 Day 36 35 days post end of infusion (±24 hours)
15 Day 43 42 days post end of infusion (±48 hours)
16 Day 50 49 days post end of infusion (±48 hours)
17 Day 57 56 days post end of infusion (±48 hours)
Secondary outcome [1] 369746 0
To characterise the PK profile of ISU305 and Soliris in serum following a single 300 mg IV infusion. Pharmacokinetic parameters for investigational product will be calculated using non-compartmental analysis. The following additional PK parameters will also be analysed:
• AUC(0-last);
• Cmax;
• Time to Cmax (tmax);
• Terminal half-life (t½);
• Vz;
• lambda-z;
• Clearance;
• %AUCextrap;
Timepoint [1] 369746 0
Sample Number: Day: Timepoint

1 Day 1 Pre-dose (within 30 minutes prior to dosing)
2 Day 1 End of infusion (35 minutes post start of infusion) (±1 minute)
3 Day 1 4 hours post end of infusion (±2 minutes)
4 Day 1 8 hours post end of infusion (±5 minutes)
5 Day 1 12 hours post end of infusion (±5 minutes)
6 Day 2 24 hours post end of infusion (±5 minutes)
7 Day 3 48 hours post end of infusion (±3 hours)
8 Day 5 96 hours post end of infusion (±3 hours)
9 Day 8 168 hours post end of infusion (±3 hours)
10 Day 11 10 days post end of infusion (±3 hours)
11 Day 15 14 days post end of infusion (±3 hours)
12 Day 22 21 days post end of infusion (±24 hours)
13 Day 29 28 days post end of infusion (±24 hours)
14 Day 36 35 days post end of infusion (±24 hours)
15 Day 43 42 days post end of infusion (±48 hours)
16 Day 50 49 days post end of infusion (±48 hours)
17 Day 57 56 days post end of infusion (±48 hours)
Secondary outcome [2] 369747 0
To compare the safety and tolerability of ISU305 to Soliris following a single 300 mg IV infusion. The following endpoints will be assessed.
• Treatment emergent adverse events (TEAEs);
• Adverse events of special interest (AESI - infusion related reactions and meningitis);
• Safety clinical laboratory assessments (haematology, clinical chemistry and urinalysis);
• Vital signs;
• 12-Lead electrocardiogram (ECG).
Timepoint [2] 369747 0
Study visits Day 3, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 36, Day 43 and Day 50. Final FU will be Day 57.
Secondary outcome [3] 369748 0
To compare the immunogenicity of ISU305 to Soliris following a single 300 mg IV infusion. The secondary endpoint measured will include anti-drug antibodies and neutralising antibodies.
Timepoint [3] 369748 0
Blood samples for the determination of anti-drug antibodies and neutralising antibodies will be collected from all subjects on:
• Day 1: 30 minutes prior to investigational product administration;
• Day 29;
• Day 57.
Secondary outcome [4] 369749 0
To assess the changes in 50% total haemolytic complement activity of ISU305 to Soliris following a single 300 mg IV infusion.The secondary endpoint measured will include CH50; as assessed by area between the effect curve.
Timepoint [4] 369749 0
Blood samples for the determination of anti-drug antibodies and neutralising antibodies will be collected from all subjects on:
• Day 1: 30 minutes prior to investigational product administration;
• Day 29;
• Day 57.

Eligibility
Key inclusion criteria
To be eligible for study entry, subjects must satisfy all of the following criteria:
1. Be able to give voluntary written informed consent prior to any study related procedures before any study-specific procedures are performed;
2. Documented evidence of prior vaccination with meningococcal vaccine for strains A, C W, Y and B (Note: vaccination may take place during the screening period, at least 14 days prior to dosing);
3. Willing to take prophylactic antibiotics (ciprofloxacin 500 mg weekly) for 4 weeks at the study unit, starting on the evening of Day 1 after dosing;
4. Availability for the entire study period and willing to commit to staying for the required time in the study unit;
5. Male subjects aged between 18 years and 45 years;
6. Body mass index (BMI) between 18.00 and 30.00 kg/m2;
7. Weight between 50 kg and 90 kg;
8. A male subject is eligible to participate if he agrees to take appropriate contraceptive measures from Screening and until 5 months after the investigational product administration and refrains from donating sperm for 5 months after the investigational product administration;
9. Subject must be healthy as determined by clinical investigator, based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluations (haematology, clinical chemistry and urinalysis).
Note: physical examination, vital signs, 12-lead ECG and clinical laboratory evaluations must be normal or clinically acceptable as determined by the investigator at all pre-dose assessments.
Minimum age
18 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects will be excluded from the study if one or more of the following criterion are applicable:
1. Hypertension (defined as a systolic blood pressure > 140 mmHg and/or a diastolic blood pressure > 90 mmHg confirmed by a single repeat measurement that same day) or a history of hypertension requiring intervention;
2. Proteinuria (with a urine dipstick value of 1+ or above);
3. Known or suspected hereditary complement deficiency;
4. Presence or suspicion of active bacterial infection, in the opinion of the investigator;
5. History of meningococcal infection;
6. History or evidence of a clinically significant disorder (including psychiatric), condition, or disease that, in the opinion of the investigator and medical monitor or designee, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;
7. History or presence of conditions known to interfere with the distribution, metabolism, or excretion of drugs;
8. Use of any over the counter (OTC) or prescription medications within the 14 days or 5 half-lives (whichever is longer), prior to receiving investigational product. Acetaminophen/paracetamol (up to 4 g per day) for analgesia will be allowed. Previous immunoglobulin or iron supplementation within 3 months prior to the screening visit is not allowed. Vitamin and herbal medicines use can be allowed per agreement between the investigator and the medical monitor, and communicated to the Sponsor;
9. History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study;
10. Prior exposure to eculizumab or related compounds (i.e., a monoclonal antibody that specifically binds to the complement protein C5);
11. Known or suspected sensitivity to products derived from mammalian cell lines;
12. Donated blood (including blood products) or experienced loss of blood greater than or equal to 500 mL within 3 months of screening;
13. Positive screen for alcohol and/or potential drugs of abuse (cannabis and metabolites, cocaine and metabolites, amphetamines, barbiturates, benzodiazepines and opioids) by urine drug screen. A positive screen may be repeated once at the discretion of the investigator;
14. History of alcohol or drug abuse or drug addiction (including cannabis products) within the last 12 months prior to screening;
15. Smokes >10 cigarettes per day within 3 months of screening or is not able to refrain from smoking during the inpatient component of the study;
16. Subject should refrain from drinking alcohol within 72 hours prior to Day -1, and should not consume more than 14 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits) throughout the study;
17. Positive screen for human immunodeficiency virus (HIV1 and 2), hepatitis B virus surface antigen, or hepatitis C virus;
18. Subjects with a history of migraines, cluster headaches, clinically significant tension headaches or headaches requiring evaluation by a neurologist;
19. History of relevant drug and/or food allergies, and/or latex allergy;
20. Vaccination within 30 days prior to entry into the study except study required meningococcal vaccination or planning a vaccination before the Day 57 end of study visit;
21. Positive result for tuberculosis using QuantiFERON-TB Gold test at the screening visit or, if indeterminant result on first test, positive or indeterminant on repeat QuantiFERON-TB Gold test;
22. Subject is a family member or employee of the investigator/sponsor;
23. History of or current invasive malignancy (excluding basal cell carcinoma that has been resected with no evidence of metastatic disease for 3 years);
24. History of penicillin allergies;
25. History of hypersensitivity to any member of the quinolone class of antimicrobial agents ;
26. History of ongoing seborrheic dermatitis and eczema;
27. Known hypersensitivity to any component of Bexsero and Menactra including diphtheria toxoid, or a life-threatening reaction after previous administration of a vaccine containing similar components;
28. Receiving or has received other investigational drugs (or is currently using an investigational device) within 3 months or 5 half-lives (whichever is longer) prior Day 1.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
NA
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis
The total sample size for this study is 148 (74 in each arm) after taking a 10% dropout rate into account. In general, data will be summarised using descriptive statistics (mean, median, standard deviation, minimum and maximum) or frequency counts and percentages, as appropriate to the type of data. Baseline will be defined as the last available, valid, non-missing assessment prior to dosing. The primary endpoint of the study is the evaluation of AUC(0-inf).

The following additional PK parameters will also be analysed:
• AUC(0-last);
• Cmax;
• Time to Cmax (tmax);
• Terminal half-life (t½);
• Vz;
• Terminal rate constant (slowest rate constant of the disposition)
• Clearance;
• %AUCextrap;

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/06/2019
Actual
26/06/2019
Date of last participant enrolment
Anticipated
26/08/2019
Actual
20/11/2019
Date of last data collection
Anticipated
22/10/2019
Actual
21/01/2020
Sample size
Target
148
Accrual to date
Final
148
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13660 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 26342 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 21436 0
New Zealand
State/province [1] 21436 0
Christ Church

Funding & Sponsors
Funding source category [1] 302600 0
Commercial sector/Industry
Name [1] 302600 0
ISU Abxis
Country [1] 302600 0
Korea, Republic Of
Primary sponsor type
Commercial sector/Industry
Name
ISU Abxis
Address
5th fl. Global R&D Center Building C, 22 Daewangpangyoro 712-beongil, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea,13488
Country
Korea, Republic Of
Secondary sponsor category [1] 302515 0
None
Name [1] 302515 0
Address [1] 302515 0
Country [1] 302515 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303235 0
Health and Disability Ethics Committees
Ethics committee address [1] 303235 0
Health and Disability Ethics Committees
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 303235 0
New Zealand
Date submitted for ethics approval [1] 303235 0
18/03/2019
Approval date [1] 303235 0
10/04/2019
Ethics approval number [1] 303235 0
18/CEN/249/AM01

Summary
Brief summary
ISU305 is being developed by ISU Abxis as a proposed biosimilar to eculizumab (Soliris® marketed by Alexion in the European Union [Soliris]). Soliris is approved for the treatment of patients with paroxysmal nocturnal haemoglobinuria (PNH) or atypical haemolytic uraemic syndrome (aHUS), disorders associated with dysregulated complement activation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92950 0
Dr Chris Wynne
Address 92950 0
Christchurch Clinical Studies Trust Ltd
Level 4, 264 Antigua Street, Christchurch 8011, NZ
Country 92950 0
New Zealand
Phone 92950 0
+64 3 3729477 
Fax 92950 0
Email 92950 0
[email protected]
Contact person for public queries
Name 92951 0
Sonia Krammer
Address 92951 0
Christchurch Clinical Studies Trust Ltd
Level 4, 264 Antigua Street, Christchurch 8011, NZ
Country 92951 0
New Zealand
Phone 92951 0
+6433729477
Fax 92951 0
Email 92951 0
[email protected]
Contact person for scientific queries
Name 92952 0
Chris Wynne
Address 92952 0
Christchurch Clinical Studies Trust Ltd
Level 4, 264 Antigua Street, Christchurch 8011, NZ
Country 92952 0
New Zealand
Phone 92952 0
+64 3 3729477 
Fax 92952 0
Email 92952 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The details of IPD sharing are TBC at this stage.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

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No additional documents have been identified.