Autoimmune disorders
Conditions
Interventions
Six volunteers will receive Immucothel/Alhydrogel, six will receive
Immucothel/Alhydrogel and tetanus toxoid, and three volunteers will receive
placebo (saline).
KLH antigen
tetanus antigen
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Eligible subjects must meet all of the following inclusion criteria at screening: 1. Healthy male subjects, 18 to 45 years of age (inclusive). The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease following a detailed medical history and a complete physical examination including vital signs, laboratory measurements and 12-lead ECG; 2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum bodyweight of 50 kg; 3. Previous immunization with tetanus toxoid as reported by the subject; 4. Willing to give written informed consent and willing and able to comply with the study protocol.
Exclusion criteria
Exclusion criteria: Eligible subjects must meet none of the following exclusion criteria at screening: 1. Any disease associated with immune system impairment, including auto-immune diseases, HIV, any confirmed history of severe allergic reaction and transplantation patients; 2. Known infection requiring antibiotic therapy within the last three months prior to the study 3. Previous known exposure to Immucothel® or KLH; 4. Any adverse immune reaction following immunization with tetanus toxoid; 5. Known allergy against Thiomersal®, which is a stabilizer in the tetanus toxoid immunization; 6. Received immunosuppressive or immunomodulatory medication within 30 days prior to enrollment or planned to use during the course of the study; 7. Use of medication (prescription or over-the-counter) within 21 days of the first study day, or less than 5 half-lives (whichever is longer), and during the course of the study; 8. Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year; 9. Previous participation in an investigational drug or device study involving the dosing of a biological targeted at any immune pathway within one year prior to screening; 10. Loss or donation of blood over 500 mL within three months prior to screening; 11. Any (medical) condition that would, in the opinion of the investigator, potentially compromise the safety or compliance of the subject or may preclude the subjects* successful completion of the clinical trial. 12. History of Schistosomiasis (infection with Schistosoma parasite). 13. History or current nicotine use in access of 5 cigarettes per day, or unable not to smoke during the course of the study, defined as between the screening visit and the final visit. 14. Tetanus toxoid immunization within the last 10 years before study participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy endpoints * KLH-specific and tetanus toxoid-specific IgG and IgM titers (ELISA); * OX40 and OX40L expression by flow cytometric analysis, on T-cells, B-cells and monocytes; * Ex vivo lymphocyte proliferation upon Immucothel challenge of isolated PBMCs. Response quantification by flow cytometry (OX40, OX40L), proliferation (by CellTrace Violet), and (optionally) cytokine release (e.g. IL-2, IL-6, IL10, IL-17 and IFNy); * mRNA analysis of lymphocyte populations (T-helper cells, cytotoxic T-cells and T-regulatory cells) sorted by immunomagnetic selection. Readouts may entail OX40, OX40L, and optionally other cell activation markers; * Erythema, swelling and redness at the sites of intradermal KLH (Delayed Type Hypersensitivity [DTH] upon intradermal injection of 1 *g Immucothel in 10*L, on the flexor aspect of the forearm). Tolerability / safety endpoints - Treatment-emergent (serious) adverse events ((S)AEs). - Concomitant medication - Clinical laboratory tests o Haematology o Chemistry o Urinalysis - Vital signs o Pulse Rate (bpm) o Systolic blood pressure (mmHg) o Diastolic blood pressure (mmHg) - Electrocardiogram (ECG) o Heart Rate (HR) (bpm), PR, QRS, QT, QTcF - Immucothel intramuscular injection site responses. | — |
Countries
The Netherlands
Outcome results
None listed