Randomized, placebo-controlled multiple dose study to evaluate the effect of hydroxychloroquine on the general immuno-competence in young and elderly healthy male volunteers

1. Signed informed consent prior to any study-mandated procedure
2. Healthy male subjects, 18 to 30 years or 65 to 75 years of age, inclusive at
screening.
3. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, and with a minimum
weight of 50 kg.
4. Has the ability to communicate well with the Investigator in the Dutch
language and willing to comply with the study restrictions.

1. Known hypersensitivity reaction to chloroquine, hydroxychloroquine or
4-aminoquinolines;
2. 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 (including a known
history of long QT syndrome, known history of retinal disease, G6PD deficiency,
porphyria, psoriasis, myasthenia gravis, liver disease, diabetes mellitus type
I and II, existing hearing loss and current or previous history of a relevant
psychiatric disorder i.e. major depressive disorder, bipolar disorder,
schizophrenia or another psychotic disorder or current of previous suicidality
irrespective of an associated psychiatric disorder);
3. Clinically significant abnormalities, as judged by the investigator, in
laboratory test results (including hepatic and renal panels, complete blood
count, 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;
4. Signs or symptoms of any active infection within two weeks prior to first
dosing.
5. Positive SARS-CoV-2 qPCR test pre-dose.
6. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus antibody (HIV Ab) at screening;
7. Systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and
diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg and
considered to be of clinical relevance by the investigator;
8. Abnormal findings in the resting ECG, including but not limited to QTcF> 450
msec.
9. Use of any medications (prescription or over-the-counter [OTC]), within 14
days of study drug administration, or less than 5 half-lives (whichever is
longer). Exceptions will only be made if the rationale is clearly documented by
the investigator;
10. Participation in an investigational drug study (last dosing of previous
study was within 90 days prior to first dosing of this study);
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, tranquillizers, or any other addictive agent and
unable to abstain from alcohol use from at least 24 hours before every visit;
12. Positive test for drugs of abuse at screening or pre-dose. Drugs test may
be repeated;
13. Smoker of more than 10 cigarettes per week prior to screening or who use
tobacco products equivalent to more than 10 cigarettes per week and unable to
abstain from smoking from at least 7 days before first dosing until the last
return visit (day 10);
14. Any confirmed significant allergic reactions (urticaria or anaphylaxis)
against any drug, or multiple drug allergies (non-active hay fever is
acceptable);
15. Loss or donation of blood over 500 mL within three months prior to
screening or intention to donate blood or blood products during the study;
16. 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.