Immune System Diseases
Conditions
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.
Interventions
DRUGKY1005
A human anti-OX40 ligand monoclonal antibody
DRUGPlacebo
Matched placebo
Sponsors
Kymab Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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 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. |
| 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 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. |
| Occurrence of all treatment-related adverse events | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. |
Secondary
| Measure | Time frame |
|---|---|
| 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. |
| Clearance (CL) | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. |
| 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. |
| Apparent volume of distribution during terminal phase (Vz) | Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum anti-KY1005 antibody titres | 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. |
| Delayed Type Hypersensitivity response in the skin after intradermal injection of Immucothel® or saline measured by LSCI photography (cohorts 4-8 only) | Day 85 and 87 | Change in basal flow and flare |
| 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) | Day 85 and 87 | Change in skin colour a and haemoglobin level (concentration of redness per unit area relative to region of interest) |
| Neo-antigen and recall antigen immunological responses (cohorts 4-8 only) | 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. |
| Immunophenotype and OX40/OX40L expression | Cohorts 1- 8: up to day 85. | Changes in specific cell subsets and expression of OX40/OX40L on each subset (where evaluable). |
Countries
Netherlands
Outcome results
None listed