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

Phase 1

Completed

• Conditions: Paroxysmal nocturnal haemoglobinuria (PNH); Atypical haemolytic uraemic syndrome (aHUS); Inflammatory and Immune System - Other inflammatory or immune system disorders; Blood - Anaemia; Renal and Urogenital - Other renal and urogenital disorders

• Registration Number: ACTRN12619000694112
• Lead Sponsor: ISU Abxis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-09
• Study Completion: 2020-01-21
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: Completed
• Sex: Male
• Target Recruitment: 148

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.

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 me

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint of the study is the evaluation of AUC(0-inf). [Sample Number: Day:Timepoint<br><br>1Day 1Pre-dose (within 30 minutes prior to dosing)<br>2Day 1End of infusion (35 minutes post start of infusion) (±1 minute)<br>3Day 14 hours post end of infusion (±2 minutes)<br>4Day 18 hours post end of infusion (±5 minutes)<br>5Day 112 hours post end of infusion (±5 minutes)<br>6Day 224 hours post end of infusion (±5 minutes)<br>7Day 348 hours post end of infusion (±3 hours)<br>8Day 596 hours post end of infusion (±3 hours)<br>9Day 8168 hours post end of infusion (±3 hours)<br>10Day 1110 days post end of infusion (±3 hours)<br>11Day 1514 days post end of infusion (±3 hours)<br>12Day 2221 days post end of infusion (±24 hours)<br>13Day 2928 days post end of infusion (±24 hours)<br>14Day 3635 days post end of infusion (±24 hours)<br>15Day 4342 days post end of infusion (±48 hours)<br>16Day 5049 days post end of infusion (±48 hours)<br>17Day 5756 days post end of infusion (±48 hours)<br>]