Immune response
Conditions
Interventions
Trade Name: Immucothel
Pharmaceutical Form:
INN or Proposed INN: immunocyanine
Other descriptive name: IMMUNOCYANINE, STANDARDISED
Concentration unit: mg milligram(s)
Concentration type: equal
Concen
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
Male
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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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 |
|---|---|
| Secondary Objective: Not applicable;Timepoint(s) of evaluation of this end point: Day 0 - day 28;Main Objective: Investigation of the immune response following immunization with Immucothel/Alhydrogel with or without tetanus. Per efficacy endpoint, the following parameters will be explored: (a) Response size; (b) Inter-individual variability of the response; (c) Time course of the response. Moreover, for each efficacy endpoint, it will be confirmed that a simultaneous administration of tetanus toxoid does not interfere (or only minimally) with the KLH response. This is valuable information to support simultaneous KLH/tetanus toxoid immunizations in the future intervention trial targeting OX40/OX40L. The data generated in the current study will allow selection of the most robust readout measures for quantification of the Immucothel/Alhydrogel-induced immune response in the future OX40/OX40L study and allow for a power analysis of studies using this model. ;Primary end point(s): • KLH-specific and tetanus toxoid-specific IgG and IgM titers (ELISA); • Ex vivo PBMC activation upon both an Immucothel® and tetanus toxoid challenge of isolated PBMCs. Response quantification by proliferation markers (for example by CellTrace Violet or BrdU) and possibly cytokine release (e.g. IL-2, IL-6, IL10, IL-17 and IFN?); • Ex vivo whole blood activation upon both an Immucothel® and tetanus toxoid challenge. Response quantification by flow cytometric analysis of T cell activation markers; • Erythema and swelling at the sites of intradermal KLH (Delayed Type Hypersensitivity [DTH] upon intradermal injection of 1 µg Immucothel® in 10?L, on the flexor aspect of the forearm). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Not applicable;Secondary end point(s): Not applicable | — |
Countries
Netherlands
Contacts
Public ContactResearch Director
Centre for Human Drug Research
Outcome results
None listed