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.

Recruiting

Conditions: Acute and chronic inflammatory disorders and Rheumatic Arthritis
Acute and chronic inflammatory disorders
Autoimmune disorders
10003816

Registration Number: NL-OMON56333

Lead Sponsor: Citryll

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 84

Inclusion Criteria

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

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 w

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part A<br /><br>• Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at<br /><br>every study visit<br /><br>• Concomitant medication throughout the study at every study visit<br /><br>• Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic<br /><br>blood pressure (mmHg)) as per assessment schedule<br /><br>• Clinical laboratory tests (Haematology, blood chemistry and urinalysis) as<br /><br>per assessment schedule<br /><br>• ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF) as per<br /><br>assessment schedule<br /><br><br /><br>• PK parameters of CIT-013 by non-compartmental analysis of the serum<br /><br>concentration-time data: Single ascending dose:<br /><br>• AUCinf, AUClast, CL, Cmax, t1/2, tlag, tmax, Vz<br /><br>• Dose-normalized PK parameters: AUCinf, AUClast, Cmax</p><br>

Secondary Outcome Measures