Acute and chronic inflammatory disorders and Rheumatic Arthritis Acute and chronic inflammatory disorders Autoimmune disorders
Conditions
Interventions
Part A
- Cohort 1: 0.1 mg/kg, 3 subjects CIT-013 / 3 subjects placebo
- Cohort 2: 0.3 mg/kg, 6 subjects CIT-013 / 2 subjects placebo
- Cohort 3: 0.9 mg/kg, 6 subjects CIT-013 / 2 subjects placebo
- Co
Sponsors
Citryll
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A • Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit • Concomitant medication throughout the study at every study visit • Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic blood pressure (mmHg)) as per assessment schedule • Clinical laboratory tests (Haematology, blood chemistry and urinalysis) as per assessment schedule • ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF) as per assessment schedule • PK parameters of CIT-013 by non-compartmental analysis of the serum concentration-time data: Single ascending dose: • AUCinf, AUClast, CL, Cmax, t1/2, tlag, tmax, Vz • Dose-normalized PK parameters: AUCinf, AUClast, Cmax | — |
Secondary
| Measure | Time frame |
|---|---|
| Part B • Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit • Concomitant medication throughout the study at every study visit • Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic blood pressure (mmHg)) as per assessment schedule • Clinical laboratory tests (Haematology, blood chemistry and urinalysis) as per assessment schedule • ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF) as per assessment schedule •PK parameters of CIT-013 by non-compartmental analysis of the serum concentration-time data after the single dose:: •AUCinf, AUClast, CL, Cmax, t1/2, tmax, Vz •Dose-normalized PK parameters: •AUCinf, AUClast, Cmax Change from baseline to each time point of measurement during each treatment period: • Circulating cytokines and/or chemokines induced by in vivo LPS challenge, • Circulating immune cells induced by in vivo LPS challenge, • Circulating NET components induced by in vivo LPS challenge Part C • Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit, including frequency, duration and severity of local signs and symptoms at the injection site. • Concomitant medication throughout the study at every study visit • Vital signs (Pulse Rate (bpm), Systolic blood pressure (mmHg), Diastolic blood pressure (mmHg)) as per assessment schedule • Clinical laboratory tests (Haematology, blood chemistry and urinalysis) as per assessment schedule • ECG parameters (Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF) as per assessment schedule • PK parameters of CIT-013 by non-compartmental analysis of the serum concentration-time data: Single ascending dose: • AUCinf, AUClast, CL, Cmax, t1/2, tlag, tmax, Vz • Dose-normalized PK parameters: AUCinf, AUClast, Cmax Part D: • Treatment-emergent (serious) adverse events ((S)AEs) throughout the study at every study visit, including frequency, duration and severity of local signs a | — |
Countries
Netherlands
Outcome results
None listed