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ID
Source
Brief title
Health condition
Immune System disorders /Immune Diseases
Sponsors and support
Intervention
Outcome measures
Primary outcome
• KLH-specific B cell responses
• KLH-specific T cell responses
• KLH-driven skin response after intradermal KLH challenge
Secondary outcome
• KLH-specific immune response (T and B cells)
• KLH-driven skin response after intradermal KLH challenge (LSCI / Multispectral)
• Treatment-emergent (serious) adverse events ((S)AEs)
• Concomitant medication
• Toxicity Grading Scale
Background summary
In previous studies (CHDR1825, CHDR1829 and CHDR1701, CHDR1647), healthy volunteers were immunized once with intramuscular KLH after which they were challenged with KLH intradermally. Although this model has been proven to be valuable so far, there is room for further refinement and more thorough mechanistic profiling. The current study will evaluate the effect of repeated immunizations. Compared to a single immunization, this regimen is expected to enhance the humoral and cellular response to KLH, thereby potentially enhancing the local skin response upon intradermal rechallenge. This approach should enlarge the DTH response window, and overall reduce the variability of the response. In addition, the current study will evaluate the skin response to injected KLH over a time course of 48 hours, rather than a single assessment at 48 hours, and include in-depth molecular and cellular evaluations of blister exudate and skin biopsies. This approach will increase our understanding of the physiological mechanisms involved in the KLH response, and as
such guide the application of the model for future clinical pharmacology trials.
Study objective
Primary
To characterize systemic and local KLH-specific B and T cell responses by repeated KLH immunizations
Secondary
To characterize the molecular basis of the KLH-driven skin response (acute versus delayed response, Th1 versus Th2 response)
To explore the correlation between antibody, T cell, and skin responses
Study design
Dag – 42(screening) till EOS
Intervention
Immucothel® (Biosyn), the 400 kDa subunit of keyhole limpet hemocyanin (KLH). Placebo will consist of 0.9% NaCl.
Inclusion criteria
1. Signed informed consent prior to any study-mandated procedure;
2. Healthy male subjects, 18 to 45 years of age (inclusive). Health status is defined by absence or evidence of any
active or chronic disease following a detailed medical and surgical history, a complete physical examination
including vital signs, 12-lead ECG, haematology, blood chemistry, blood serology and urinalysis. In the case of
uncertain or questionable results, tests performed during screening may be repeated before randomization to
confirm eligibility or judged to be clinically irrelevant for healthy subjects;
3. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and with a minimum bodyweight of 50 kg;’
4. Fitzpatrick skin type I-III.
5. Has the ability to communicate well with the Investigator in the Dutch language and willing and able to comply
with the study restrictions.
Exclusion criteria
1. Evidence of any active or chronic disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted, if judged by the Investigator to have no clinical relevance;
2. Clinically significant abnormalities, as judged by the Investigator, in laboratory test results (including haematology panel, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests
performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects;
3. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening;
4. Any disease associated with immune system impairment, including immune mediated diseases, transplantation patients and any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug or multiple drug allergies (non-active hay fever is acceptable);
5. Use of any medications (prescription or over-the-counter [OTC]), within 21 days prior to initial KLH immunization, or less than 5 half-lives (whichever is longer). An exception is made for paracetamol (up to 4 g/day). Other exceptions will only be made if the rationale is clearly documented by the Investigator;
6. Use of immunosuppressive or immunomodulatory medication within 30 days prior to initial KLH immunization or planned to use during the course of the study;
7. Any vaccination within 30 days prior to initial KLH immunization or planned during the course of the study with exception of vaccination for SARS-CoV-2;
8. Vaccination for SARS-CoV-2 within 14 days prior to initial KLH immunization, or planned during the course of the study;
9. Use of antibiotic therapy within 90 days prior to initial KLH immunization or planned to use during the course of the study;
10. Alcohol will not be allowed from at least 24 hours before screening and each scheduled visit. At other times during the course of the study no more than 2 units of alcohol per day will be allowed;
11. History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 14 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquillisers, or any other addictive agent;
12. Positive test for drugs of abuse or alcohol breath test at screening;
13. Smoker of more than 5 cigarettes per day prior to screening or who use tobacco products equivalent to more than 5 cigarettes per day and unable to abstain from smoking whilst in the unit.
14. Previous known exposure to Immucothel® or KLH;
15. History of Schistosomiasis (infection with Schistosoma parasite);
16. Participation in an investigational drug or device study (last dosing of previous study was within 90 days prior to initial KLH immunization of this study and participation more than 4 times a year);
17. Loss or donation of blood over 500 mL within 90 days prior to screening or intention to donate blood or blood products during the study;
18. Have any current and / or recurrent clinically significant skin condition at the treatment area (i.e. atopic dermatitis); including tattoos;
19. Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
Design
Recruitment
IPD sharing statement
Plan description
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
NTR-new | NL9782 |
CCMO | NL78698.056.21 |
OMON | NL-OMON50194 |