A Study of KY1005 in Healthy Volunteers

Study Overview
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Brief Summary
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This is a single and multiple ascending dose, placebo-controlled, double-blind, Phase 1 study to evaluate the safety and tolerability of KY1005 in healthy volunteers.

Official Title
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A Single and Multiple Ascending Dose, Placebo-Controlled, Double-Blind, Phase 1 Study of KY1005 in Healthy Volunteers

Conditions
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Immune System Diseases

Intervention / Treatment
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* Drug: KY1005
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must fulfil all of the following criteria for entry into the study. Volunteer to participate in the clinical trial and provide signed informed consent. Male, aged 18 to 45 years. Subjects with a female spouse/partner of childbearing potential must agree to use effective birth control starting at screening and continuing throughout the clinical study period and for a period of up to 6 months after study completion. Cohorts 4 to 8: previous immunisation with tetanus toxoid (TT) but not within 6 months prior to the screening visit as reported by the volunteer. Cohorts 4 to 8: anti-TT immunoglobulin G (IgG) response > 0.1 IU/mL and ≤ 50 IU/mL at screening. Exclusion Criteria: Subjects fulfilling any of the following exclusion criteria are not eligible for entry into the study. Experiencing a clinically significant, chronic or acute infection requiring treatment at screening or prior to first IMP administration. A body weight of ≤ 60.0 kg or ≥ 120.0 kg. A body mass index ≤ 18.0 or ≥ 30.0 kg/m2. History of disease of the central nervous system, cardiovascular system, kidney, liver, digestive system, respiratory system or metabolic/endocrine system or suffered from other disease that in the opinion of the principal investigator (or medically qualified designee) may make participation unsafe for the subject or interfere with trial evaluations or otherwise considered clinically significant. History of immunological abnormality (e.g., immune suppression, severe allergy or anaphylaxis) that in the opinion of the principal investigator (or medically qualified designee) may make participation unsafe for the subject or interfere with trial evaluations or otherwise considered clinically significant. History of malignancy, or known current malignancy. Leukocyte absolute value < 3.50 × 10^9/L or > 9.50 × 10^9/L, neutrophil absolute value < 1.8 × 10^9/L, platelet counts < 100 × 10^9/L, haemoglobin < 12.0 g/dL. Taken part in other clinical trials within 3 months of screening for this study or > four trials in the year preceding the first IMP administration. Donated or lost more than 500 mL of blood or plasma within 3 months of screening. Prescription drug taken within 2 weeks of screening or likely to be taken during the trial. Live immunisation within 3 months of screening or plans to receive such immunisation during the clinical trial or for a period of 6 months after the end of the trial. Taking or likely to take over-the-counter medication, including herbal medicines, that in the opinion of the principal investigator (or medically qualified designee) may make participation unsafe for the subject or interfere with trial evaluations. Hepatitis B surface antigen, Hepatitis C antibody, or Human Immunodeficiency Virus positive. History of or current drug or substance abuse considered significant by the principal investigator (or medically qualified designee) including a positive urine drug screen. Current smoker and/or regular user of other nicotine-containing products (e.g., patches). Average consumption of more than 14 units of alcohol/week. Clinically significant abnormal screening values in clinical (electrocardiograms (ECGs), vital signs, physical examination) and laboratory tests in the opinion of the principal investigator (or medically qualified designee). Cannot communicate adequately or cannot commit to full participation in all trial procedures. For Cohorts 4 to 8: Confirmed previous exposure to immunocyanins, such as keyhole limpet haemocyanin (KLH); Known allergy to thiomersal or other components of Tetanus vaccine or Immucothel®; History of schistosomiasis. Any observation that, in the opinion of the principal investigator (or medically qualified designee) makes the subject unsuitable for participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohorts 1-3<br>Healthy volunteers will receive single rising doses of KY1005 or placebo | Drug: KY1005<br>* A human anti-OX40 ligand monoclonal antibody<br>Drug: Placebo<br>* Matched placebo<br>|
| Experimental: Cohorts 4-8<br>Healthy volunteers will receive multiple rising doses of KY1005 or placebo | Drug: KY1005<br>* A human anti-OX40 ligand monoclonal antibody<br>Drug: Placebo<br>* Matched placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of all treatment-related adverse events |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. | 
| Changes in vital signs (as a measure of safety and tolerability) |  | Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre- first infusion up to day 92. | 
| Changes in laboratory safety data (as a measure of safety and tolerability) |  | Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre-first infusion up to day 92. | 
| Changes in anti-viral antibody levels and viral DNA (as a measure of safety and tolerability) |  | Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre-first infusion up to day 92. | 
| Changes in acute cytokines (as a measure of safety and tolerability) |  | Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre-first infusion up to day 92. | 
| Changes in electrocardiograms (as a measure of safety and tolerability) |  | Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre-first infusion up to day 92. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) following the first, second and third infusions for each KY1005 dose/dosing group |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. | 
| Time to maximum observed serum concentration (tmax) following the first, second and third infusions for each KY1005 dose/dosing group |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. | 
| Trough concentrations (Cmin) following the first and second infusions and 28 days after the third infusion |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. | 
| Areas under the plasma concentration-time curves (AUC) |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. | 
| Clearance (CL) |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. | 
| Apparent volume of distribution during terminal phase (Vz) |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. | 
| Apparent volume of distribution at steady state (Vss) |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. | 
| Half-life (t½) |  | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. |