A Study of KY1005 in Healthy Volunteers

Immune System Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03161288
• Other study ID #: KY1005-CT01
• Status: Completed
• Phase: Phase 1
• Start date: May 29, 2017
• Est. completion date: March 30, 2018

Study information

• Verified date: August 2019
• Source: Kymab Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: March 30, 2018
• Est. primary completion date: March 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Immune System Diseases

Intervention

Drug:
• KY1005
A human anti-OX40 ligand monoclonal antibody
• Placebo
Matched placebo

Locations

Country	Name	City	State
Netherlands	Centre for Human Drug Research	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Kymab Limited

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.
Other	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.
Other	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
Other	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
Other	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
Primary	Occurrence of all treatment-related adverse events		Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	Areas under the plasma concentration-time curves (AUC)		Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92.
Secondary	Clearance (CL)		Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92.
Secondary	Apparent volume of distribution during terminal phase (Vz)		Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92.
Secondary	Apparent volume of distribution at steady state (Vss)		Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92.
Secondary	Half-life (t½)		Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92.