A Study of KY1005 in Healthy Volunteers

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

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.

Study Overview

• Status: Completed
• Conditions: Immune System Diseases
• Intervention / Treatment: Drug: Placebo; Drug: KY1005

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands
    • Centre For Human Drug Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Subjects must fulfil all of the following criteria for entry into the study.

1. Volunteer to participate in the clinical trial and provide signed informed consent.
2. Male, aged 18 to 45 years.
3. 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.
4. 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.
5. 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.

1. Experiencing a clinically significant, chronic or acute infection requiring treatment at screening or prior to first IMP administration.
2. A body weight of ≤ 60.0 kg or ≥ 120.0 kg.
3. A body mass index ≤ 18.0 or ≥ 30.0 kg/m2.
4. 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.
5. 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.
6. History of malignancy, or known current malignancy.
7. 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.
8. 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.
9. Donated or lost more than 500 mL of blood or plasma within 3 months of screening.
10. Prescription drug taken within 2 weeks of screening or likely to be taken during the trial.
11. 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.
12. 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.
13. Hepatitis B surface antigen, Hepatitis C antibody, or Human Immunodeficiency Virus positive.
14. History of or current drug or substance abuse considered significant by the principal investigator (or medically qualified designee) including a positive urine drug screen.
15. Current smoker and/or regular user of other nicotine-containing products (e.g., patches).
16. Average consumption of more than 14 units of alcohol/week.
17. 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).
18. Cannot communicate adequately or cannot commit to full participation in all trial procedures.

19. For Cohorts 4 to 8:

    1. Confirmed previous exposure to immunocyanins, such as keyhole limpet haemocyanin (KLH);
    2. Known allergy to thiomersal or other components of Tetanus vaccine or Immucothel®;
    3. History of schistosomiasis.
20. Any observation that, in the opinion of the principal investigator (or medically qualified designee) makes the subject unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum anti-KY1005 antibody titres	Change in serum anti-KY1005 antibody titres from pre-infusion.	Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92.
Immunophenotype and OX40/OX40L expression	Changes in specific cell subsets and expression of OX40/OX40L on each subset (where evaluable).	Cohorts 1- 8: up to day 85.
Neo-antigen and recall antigen immunological responses (cohorts 4-8 only)	Change in anti-tetanus toxoid immunoglobulin G (IgG) and immunoglobulin M (IgM) titres in serum and anti-Immucothel® IgG and IgM titres in serum.	up to day 85
Delayed Type Hypersensitivity response in the skin after intradermal injection of Immucothel® or saline measured by Antera 3D® camera image analysis (cohorts 4-8 only)	Change in skin colour a and haemoglobin level (concentration of redness per unit area relative to region of interest)	Day 85 and 87
Delayed Type Hypersensitivity response in the skin after intradermal injection of Immucothel® or saline measured by LSCI photography (cohorts 4-8 only)	Change in basal flow and flare	Day 85 and 87

Collaborators and Investigators

• Sponsor: Kymab Limited
• Investigators: Principal Investigator: Jacobus Burggraaf, Centre For Human Drug Research

Publications and helpful links

General Publications

• Saghari M, Gal P, Gilbert S, Yateman M, Porter-Brown B, Brennan N, Quaratino S, Wilson R, Grievink HW, Klaassen ES, Bergmann KR, Burggraaf J, van Doorn MBA, Powell J, Moerland M, Rissmann R. OX40L Inhibition Suppresses KLH-driven Immune Responses in Healthy Volunteers: A Randomized Controlled Trial Demonstrating Proof-of-Pharmacology for KY1005. Clin Pharmacol Ther. 2022 May;111(5):1121-1132. doi: 10.1002/cpt.2539. Epub 2022 Mar 1.

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2017
• Primary Completion (Actual): March 30, 2018
• Study Completion (Actual): March 30, 2018

Study Registration Dates

• First Submitted: May 11, 2017
• First Submitted That Met QC Criteria: May 17, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases
• Other Study ID Numbers: KY1005-CT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No