A randomized, single-blind, placebo-controlled study to evaluate an oral cholera vaccination with intranasal rechallenge as adaptive immune challenge model
- Conditions
- There will be no specific condition investigated in this study10004018
- Registration Number
- NL-OMON53390
- Lead Sponsor
- Centre for Human Drug Research
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
1. Signed informed consent prior to any mandated procedure.
2. Healthy male and female subjects, 18 to 45 years of age, inclusive at
screening.
3. Body mass index (BMI) between 18 and 35 kg/m2, inclusive, and with a minimum
weight of 50 kg.
4. All subjects must practice effective contraception during the study and be
willing and able to continue contraception for at least 90 days after their
last dose of study treatment.
5. The participant has clinical laboratory evaluations (including clinical
chemistry, haematology and complete urine analysis) within the reference range
for the testing laboratory, unless the results are deemed not clinically
significant by the investigator.
6. Participants who are overtly healthy as determined by medical evaluation
including medical history, vital signs, physical examination, laboratory tests
and ECGs at Screening and on Day -2.
7. The participant should be able to take MMF / placebo 2 times per day for 6
days, and to refrain from eating 2 hours before intake.
8. Has the ability to communicate well with the Investigator in the Dutch
language and willing to comply with the study restrictions.
1. The participant has signs and/or symptoms of an infection 2 weeks prior to
dosing, or recurrent infection, or has had an infection requiring antibiotic
treatment (e.g. sepsis, pneumonia, abscess) within 42 days prior to start of
MMF / placebo administration.
2. The participant has (a history of) autoimmune disease such as multiple
sclerosis, inflammatory bowel disease, rheumatoid arthritis or other
immune-inflammatory disease.
3. The participant has a history of trauma with likely damage to the spleen, or
has had surgery to the spleen or splenectomy.
4. The participant has a known immunodeficiency.
5. Positive Hepatitis B surface antigen (HBsAg), anti-hepatitis B core,
hepatitis C, or human immunodeficiency virus antibody (HIV-Ab) at screening.
6. Serious psychiatric or medical conditions that, in the opinion of the
investigator, could interfere with treatment, compliance, or the ability to
give consent.
7. The participant has taken any over-the-counter (OTC) or any prescription
medication (with the exception of paracetamol) less than 5 half lives prior to
the first oral cholera vaccination, and considered as relevant by the
investigator.
8. Participant has received live attenuated vaccination within 42 days prior to
Screening or intends to have vaccinations during the course of the study.
SARS-CoV-2 vaccinations are not allowed 1 week prior to Screening and from 2
weeks before dosing until EOS.
9. Participant has received any investigational drug of experimental procedure
within 90 days or 5 half-lives, whichever is longer, prior to study
intervention administration, or participant was enrolled in an investigational
drug or device study within 90 days prior to first IMP dosing.
10. The participant has a history of hypersensitivity or allergies to any drug
or to any of the components of the study interventions (i.e. Dukoral oral
cholera vaccination, MMF or placebo).
11. The participant has lost or donated more than 400 mL of blood or blood
products within 90 days prior to start of MMF or placebo treatment (Day -2) or
plans to donate blood during the study.
12. The participant has had an acute, clinically significant illness or
intervention by surgeon or dentist within 14 days prior to screening.
13. Current (or within past 6 months) nicotine use in excess of 5 cigarettes
per day, or unable not to smoke during visits.
14. 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.
15. Previous vaccination against cholera or enterotoxigenic Escherichia coli.
16. Travel in the last 3 years to a country where cholera or enterotoxigenic E.
coli is prevalent.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Serum cholera antigen specific IgA levels at Day 1, 14, 18, 20 and 28.<br /><br>• Serum cholera antigen specific IgG levels at Day 1, 14, 18, 20 and 28.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Cholera antigen specific IgA in nasal secretion (measured by nasosorption) at<br /><br>-2 hours before and 1, 2, 7 and 10 days after nasal rechallenge.<br /><br>• Treatment-emergent (serious) adverse events (S)AEs.<br /><br>• Clinical safety laboratory measurements.<br /><br>• Vital signs measurements.<br /><br>• Physical examinations.</p><br>