A Study of KY1005 in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT03161288
• Recruitment Status: Completed
• First Posted: May 19, 2017
• Last Update Posted: August 29, 2019
• Sponsor: Kymab Limited
• Information provided by (Responsible Party): Kymab Limited

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Immune System Diseases	Drug: KY1005; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Single and Multiple Ascending Dose, Placebo-Controlled, Double-Blind, Phase 1 Study of KY1005 in Healthy Volunteers
• Actual Study Start Date: May 29, 2017
• Actual Primary Completion Date: March 30, 2018
• Actual Study Completion Date: March 30, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

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

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Healthy male volunteers.
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Netherlands

Centre for Human Drug Research

Leiden, Netherlands

Sponsors and Collaborators

Kymab Limited

Investigators

• Principal Investigator: Jacobus Burggraaf; Centre for Human Drug Research

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Kymab Limited
• ClinicalTrials.gov Identifier: NCT03161288
• Other Study ID Numbers: KY1005-CT01
• First Posted: May 19, 2017
• Last Update Posted: August 29, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Immune System Diseases