Primary objective:To evaluate the safety and tolerability of KY1005.Secondary objectives:To evaluate the pharmacokinetics (PK) of KY1005 following single and repeat doses.Exploratory objectives:- To evaluate the immunogenicity of KY1005;- To assess…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The safety and tolerability of KY1005 will be evaluated by
measurement/recording of:
- Adverse events (AEs);
- Vital signs;
- Laboratory safety tests;
- ECGs;
- Changes in physical examination;
- Changes in anti-viral antibody levels and viral deoxyribonucleic acid (DNA);
- Changes in acute cytokine levels (selected cohorts).
Secondary outcome
- Serum concentrations of KY1005;
- Serum anti-KY1005 antibody titres;
- Serum anti-Immucothel and anti-TT antibody titers;
- Immunophenotyping (analysis of cell subsets) in whole blood and evaluation of
OX40L and/or OX40 expression on specific cell subsets where evaluable;
- A blood sample taken before the first dose of study drug will be processed
and stored for possible future sequencing for single nucleotide polymorphisms
and/or deletions/duplications;
- Any excess serum samples after planned analyses are complete will be retained
for future evaluation of target related PD markers.
Background summary
KY1005 is a human anti-OX40 ligand (OX40L) monoclonal antibody that binds OX40L
to block interaction with its receptor, OX40. Blockade of the OX40/OX40L
co-stimulation pathway represents a scientifically plausible approach to
modulating the persistent inflammation caused by autoreactive memory T-cell
populations, and may provide a means of inducing immune tolerance to
autoantigens (e.g., in autoimmune disease) or alloantigens (e.g., following
transplants).
Study objective
Primary objective:
To evaluate the safety and tolerability of KY1005.
Secondary objectives:
To evaluate the pharmacokinetics (PK) of KY1005 following single and repeat
doses.
Exploratory objectives:
- To evaluate the immunogenicity of KY1005;
- To assess pharmacodynamics (PD) effects of KY1005 on immunophenotype (cell
subsets), OX40L and/or OX40 expression by flow cytometry (where evaluable);
- To evaluate the effect of KY1005 on neo-antigen and recall antigen in vivo
and ex vivo immunological responses in healthy volunteers;
Study design
This is a single and multiple ascending dose, placebo-controlled, double-blind,
Phase 1 study of KY1005 in eight cohorts of healthy volunteers (Cohorts 1
through 8).
The study will be carried out at one centre and will comprise dose escalation
and immunisation challenges to assess effects on immune system of KY1005 in
healthy volunteers. In Cohorts 1 to 8, two sentinel healthy volunteers (one
KY1005: one placebo) will be deployed in every cohort and the decision to
progress with the first dose to the remaining six healthy volunteers will be
made by the Principal Investigator (PI or medically qualified designee) if
there are no safety concerns 48 hours after the infusion of these sentinel
healthy volunteers.
The decision to dose escalate between cohorts will only be made after all
available safety information up to study Day 11 from at least six healthy
volunteers in the immediately preceding cohort, and all other available
cumulative safety information, as well as PK data in the case of Cohorts 4 and
6 have been reviewed by at least the PI (or medically qualified designee) and
the sponsor Study Responsible Medical Officer (SRMO) (or medically qualified
designee).
Intervention
Investigational Medicinal Products
Cohorts 1 to 3 will receive a single dose;
Cohorts 4 to 8 will receive three doses; an initial loading dose on Day 1 and
two maintenance doses of no more than a nominal 50% of the loading dose,
administered on Day 29 and Day 57;
Non-Investigational Medicinal Products
The following Non-Investigational Medicinal Products (NIMPs) will be
administered to volunteers in Cohorts 4 to 8 of the study:
Tetanus Toxoid: 0.5 mL on day 64;
Immucothel®/Alhydrogel® 2% (European Pharmacopoeia: EP): 0.1 mg/0.9 mg in 0.5
mL on day 64.
Study burden and risks
There is no direct benefit to you from taking part in the study. The results of
the study will provide valuable information for future research.
For new drugs, such as KY1005 side effects are not known yet. There may be
unexpected side effects. The effects associated a with an immune system
inhibitor medication are for instance infections.
For this study, a cannula will be inserted into one of the veins in the arm and
blood samples are taken frequently. This may result in a small local
haemorrhage which resolves after several days.
The Bennet Building (B930), Babraham Research Campus N/A
Cambridge CB22 3AT
GB
The Bennet Building (B930), Babraham Research Campus N/A
Cambridge CB22 3AT
GB
Listed location countries
Age
Inclusion criteria
Subjects must fulfill all of the following criteria for entry into the study.
1. Volunteer to participate in the clinical trial and provide signed informed consent.
2. Cohorts 1 to 8: 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
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 (BMI) * 18.0 or * 30.0 kg.
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 PI (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 PI (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 × 109/L or > 9.50 × 109/L, neutrophil absolute value < 1.8 × 109/L, platelet counts < 100 × 109/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. Cohorts 1 to 8: 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 (OTC) medication, including herbal medicines, that in the opinion of the PI (or medically qualified designee) may make participation unsafe for the subject or interfere with trial evaluations.
13. Hepatitis B surface antigen (HbsAg), Hepatitis C antibody (HCV-Ab), or Human Immunodeficiency Virus (HIV) positive.
14. History of or current drug or substance abuse considered significant by the PI (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 (electrocardiogram (ECG), vital signs, physical examination) and laboratory tests in the opinion of the PI (or medically qualified designee).
18. Cannot communicate adequately or cannot commit to full participation in all trial procedures.
19. For Cohorts 4 to 8:
a. Confirmed previous exposure to immunocyanins, such as keyhole limpet haemocyanin (KLH);
b. Known allergy to thiomersal or other components of Tetanus vaccine or Immucothel®;
c. History of schistosomiasis.
20. Any observation that, in the opinion of the PI (or medically qualified designee) makes the subject unsuitable for participation in this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR201600483920-NL |
| CCMO | NL61388.056.17 |