A Study of KY1005 in Healthy Volunteers

NCT03161288 | Completed Phase 1

• 1 other identifier: KY1005-CT01
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Immune System Diseases

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (8)

• 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.

Other Outcomes (5)

• Serum anti-KY1005 antibody titres

  Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92.

• Immunophenotype and OX40/OX40L expression

  Cohorts 1- 8: up to day 85.

• Neo-antigen and recall antigen immunological responses (cohorts 4-8 only)

  up to day 85

Study Arms (2)

Cohorts 1-3

EXPERIMENTAL

Healthy volunteers will receive single rising doses of KY1005 or placebo

Drug: KY1005; Drug: Placebo

Cohorts 4-8

EXPERIMENTAL

Healthy volunteers will receive multiple rising doses of KY1005 or placebo

Drug: KY1005; Drug: Placebo

Interventions

KY1005 DRUG

A human anti-OX40 ligand monoclonal antibody

Cohorts 1-3; Cohorts 4-8

Placebo DRUG

Matched placebo

Cohorts 1-3; Cohorts 4-8

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Healthy male volunteers.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Kymab Limited: lead

Study Sites (1)

Centre for Human Drug Research

Leiden, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 35092305 DERIVED

MeSH Terms

Conditions

Immune System Diseases

Study Officials

• Jacobus Burggraaf

  Centre for Human Drug Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2017
• First Posted: May 19, 2017
• Study Start: May 29, 2017
• Primary Completion: March 30, 2018
• Study Completion: March 30, 2018
• Last Updated: August 29, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)