A first-in-human, randomized, double-blind, placebo-controlled study to evaluate, single ascending doses of CIT-013 in healthy volunteers with and without an intravenous lipopolysaccharide challenge and repeat dosing in healthy volunteers and patients with Rheumatoid Arthritis.

lnclusion criteria part A- C, and HVs part D
Eligible subjects must meet all the following criteria at screening:
1. Healthy men or women, 18 to 55 years of age (inclusive) at screening. For
part B cohort 2 only healthy men will
be included. The health status is verified by absence of evidence of any
clinically significant activa or uncontrolled
chronic disease following a detailed medical history, a complete physical
examination including vital signs,
laboratory measurements, and 12-lead ECG;
2. Signed infonmed consent, able and willing to comply wilh the requirements of
the study protocol.
3. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, and a body weight
between 50 and 150 kg,
inclusive at screening.
4. All male and Women of Child Bearing Potenlial volunteers must practica
effeclive contraception during the
study and be willing and able to continue contraception for at least 90 days
after !heir last dose of study treatment.
5. Has the ability to communicate well with the lnvestigator in the Dutch
language and willing to comply with the
study restriclions.

lnclusion criteria part D (patients)
Eligible subjects must meet all the following criteria at screening:
1. Men or women 18 to 75 years of age (inclusive) at screening diagnosed with
RA (and fulfilling the ACR 2010 classification criteria for RA) for at least 6
months.
2. Signed informed consent, able and willing to comply with the requirements of
the study protocol.
3. Body mass index (BMI) between 18 and 35 kg/m2, inclusive, and a body weight
between 50 and 150 kg,
inclusive at screening.
4. All male and Women of Child Bearing Potential volunteers must practica
effective contraception during the
study and be willing and able to continue contraception for at least 90 days
after !heir last dose of study treatment.
5. Has the ability to communicate well with the lnvestigator in the Dutch
language and willing to comply with the
study restrictions.
6. If on conventional DMARD, should be stable on a conventional DMARD (i.e.
methotrexate, sulfasalazine, leflunomide and (hydroxy)chloroquine) (and
steroids) for at least 8 weeks and willing to continue current stable treatment
for 6 Weeks. Current treatment with
non-conventional DMARDs, including monoclonal antibodies, is not allowed.
Prednisolone <= 10 mg / day is permitted.

Exclusion criteria part A- C, and HVs in part D
Eligible subjects must not meet any of the following criteria at screening or
pre-dose:
1. Evidence (following a detailed medical history, physical examination, vital
signs, 12-lead ECG and clinical
laboratory parameters) of any active or chronic disease or condition that could
interfere with, or for which the
treatment might interfere with, the conduct of the study, or that would pose an
unacceptable risk to the subject in
the opinion of the investigator.
2. Clinically significant abnormalities, as judged by the investigator, in
laboratory test results (including hepatic and
renal panels, complete blood count, chemistry panel and urinalysis). Minor
deviations of laboratory values from the
normal range may be accepted, if judged by the lnvestigator or medically
qualified designee as not clinically
significant. 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. Any confirmed or suspected disease or condition associated with immune
system impairment, including autoimmune
diseases, HIV, asplenia or recurrent severe infections.
4. Use of chronic (more than 14 days) immunosuppressant or immunomodulatory
drugs within the 3 months prior
to IMP administration, or isolated (non-chronic) use within 30 days prior to
IMP administration.
5. Any history of severe allergie reaction(s).
6. Any confirmed significant drug hypersensitivity reactions (including skin
reactions or anaphylaxis), or known
allergies (non-active hay lever is acceptable).
7. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus
antibody (HIV Ab) at screening, or other known infection requiring systemic
antibiotic therapy within three months
prior to the study.
8. Subject has an active, uncontrolled acute or chronic systemic fungal,
bacterial, and/or viral, infection within the
past 30 days.
9. Subjects with evidence or history of clinically significant haematological,
renal, endocrine, pulmonary,
gastrointestinal, cardiovascular, hepatic, psychiatrie, neurologie diseases.
10. Subjects with a positive urine drug screen at screening or pre-dose.
11. Subject has a positive SARS-CoV-2 PCR based testwithin 72 hours prior to
receiving CIT-013.
12. History of abuse of addictive substances (alcohol, illegal substances) or
current use of more than 14 units
alcohol per week (in partAand B) and 14 units for females and 21 units lor
males (in part C), drug abuse, or
regular user of sedatives, hypnotics, tranquillisers, or any other addictive
agent.
13. Treatment with an investigational drug within 30 days or 5 half-lives
(whichever is langer) preceding the first
dose of CIT-013.
14. Use of prescription or over-the-counter (OTC) drugs, vitamins, minerals and
dietary supplements, within 7
days or 5 half-lives (whichever is langer) prior to the first dose of study
medication until EOS. Herbal supplements
and hormone replacement therapy must be discontinued 30 days prior to the first
dose of study medication until
EOS. Excluded from this list is paracetamol at doses of <4 g/day on all study
days except day 1 of part B.
Exceptions will only be made il the rationale is clea~y documented by the
investigator.
15. Receipt of live or attenuated vaccine 90 days prior to first study
intervention administration.
16. Vaccination (completion of 2nd vaccination shot il applicable) against
SARS-CoV-2 or influenza vaccinations
less than 14 days prior to first study drug administration.
17. Known hypersensitivity to any of the constituents or excipients of CIT-013
or history of relevant drug and/or
food allergy (anaphylactic, anaphylactoid reactions).
18. Excessive caffeine consumption, defined as >800 mg per day from 7 days
prior to the first dose of the study
drug until 24 hours prior to dosing. Subjects will abstain from
caffeine-containing products lor 24 hours prior to the
start of dosing until discharge trom the study unit. Caffeine quantities
defined as: one cup of coffee contains 100
mg of caffeine; one cup of tea, or one glass of cola, or portion of chocolate
(dark:100 g, milk 200 g) contains
approximately 40 mg of caffeine; one bottle of Red Bull contains approximately
80 mg of caffeine.
19. Donation (or loss) of whole bloed or plasma of 500 ml or more du ring the
12 weeks prior to CIT-013
administration.
20. Smoking > than 10 cigarettes (or equivalent) per week and/or using
nicotine-based products within 1 month
prior to CIT-013 administration and/or unwillingness to abstain trom the use of
these trom screening until EOS.
21. Any ether known factor, condition, or disease that, in the opinion of the
lnvestigator, might interfere with
treatment compliance, study conduct or interpretation of the results, or may
compromise volunteer safety.
22. Extreme exercise (e.g. marathon or triathlon) within 2 weeks of screening
(part A and B) and extreme exercise
(e.g. marathon or triathlon) within 2 weeks of screening or admission (part C).
23. Subject has participated in an intraveneus LPS challenge study before (Part
B only).

Exclusion criteria part D (patients)
Eligible subjects must not meet any of the following criteria at screening or
pre-dose:
1. Evidence (following a detailed medical history, physical examination, vital
signs, 12-lead ECG and clinical
laboratory parameters) of any active or chronic disease or condition ether than
Rheumatoid Arthritis that could
interfere with, or lor which the treatment might interfere with, the conduct of
the study, or that would pose an
unacceptable risk to the subject in the opinion of the investigator.
2. Clinically significant abnormalities, as judged by the investigator, in
laboratory test results (including hepatic and
renal panels, complete bloed count, chemistry panel and urinalysis) not
associated with Rheumatoid Arthritis,
known comorbidity or the use of concomitant medication. Minor deviations of
laboratory values from the normal
range may be accepted, il judged by the lnvestigator or medically qualified
designee as not clinically significant. 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
the patient.
3. Any confirmed or suspected disease or condition other than Rheumatoid
Arthritis, associated with immune
system impairment, including auto-immune diseases, HIV, asplenia or recurrent
severe infections. Any confirmed
significant drug hypersensitivity reactions (including anaphylaxis), or known
allergies (non-active hay fever is
acceptable).
4. Any confirmed significant drug hypersensitivity reactions (including
anaphylaxis), or known significant allergies (non-active hay fever, cat/dog
allergies or very mild non-relevant reactions are acceptable).
5. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV Ab),
or human immunodeficiency virus
antibody (HIV Ab) at screening, or other known infection requiring systemic
antibiotic therapy within three months
prior to the study.
6. Subject has an active, uncontrolled acute or chronic systemic fungal,
bacterial, and/or viral, infection within the
past 30 days.
7. Subjects with a positive urine drug screen at screening or pre-dose.
8. Subject has a positive SARS-CoV-2 PCR based test within 72 hours of
receiving CIT-013.
9. 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.
Exceptions will only be made if the rationale is clea~y documented by the
investigator.
10. Treatment with an investigational drug within 30 days or 5 half-lives
(whichever is longer) preceding the first
dose of CIT-01