An intradermal LPS challenge study to evaluate complement activation in healthy volunteers

1. Healthy male and female subjects, 18 to 45 years of age, inclusive. Healthy
status is defined by absence of evidence of any active or chronic disease
following a detailed medical and surgical history, a complete physical
examination including vital signs, 12-lead ECG, haematology, blood chemistry,
blood serology 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;

2. Body mass index (BMI) between 18 and 30 kg/m2 and a minimum weight of 50 kg,
inclusive;

3. Fitzpatrick skin type I-III (Caucasian);

4. Subjects and their partners of childbearing potential must use effective
contraception (see paragraph 4.4.2) for the duration of the study. Women of
childbearing potential are defined as all women physiologically capable of
becoming pregnant, unless they meet one of the following conditions:

-Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks
after surgical bilateral oophorectomy with or without hysterectomy;

-Post-hysterectomy.

*5. Able and willing to give written informed consent and to comply with the
study restrictions.

1. History of pathological scar formation (keloid, hypertrophic scar) or
keloids or surgical scars in the target treatment area of the upper back that
in the opinion of the investigator, would limit or interfere with dosing and/or
measurement in the trial;

2. Have any current and / or recurrent pathologically, clinical significant
skin condition at the treatment area (i.e. atopic dermatitis); including
tattoos;

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. Requirement of immunosuppressive or immunomodulatory medication within 30
days prior to enrolment or planned to use during the course of the study;

5. Use of topical medication (prescription or over-the-counter [OTC]) within 30
days of study drug administration, or less than 5 half-lives (whichever is
longer) in local treatment area

6. Participation in an investigational drug or device study within 3 months
prior to screening or more than 4 times a year.

7. Loss or donation of blood over 500 mL within three months prior to screening
or donation of plasma within 14 days of screening

8. Any history or current presence of a (medical) condition that would, in the
opinion of the investigator, potentially compromise the safety or compliance of
the patient or may preclude the patient*s successful completion of the clinical
trial.

9. 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 at
screening.*

10. Abnormal findings in the resting ECG at screening defined as:*

-QTcF> 450 or < 300 ms for men and QTcF> 470 or < 300 ms for women;*
-Notable resting bradycardia (HR*<*45 bpm) or tachycardia (HR*>*100 bpm);*
-Personal or family history of congenital long QT syndrome or sudden death;*
-ECG with QRS and/or T wave judged to be unfavorable for a consistently
accurate QT measurement (e.g., neuromuscular artefact that cannot be readily
eliminated, arrhythmias, indistinct QRS onset, low amplitude T wave, merged T-
and U-waves, prominent U waves);*
-Evidence of atrial fibrillation, atrial flutter, complete branch block,
Wolf-Parkinson-White Syndrome, or cardiac pacemaker.*

11. Chronic infection with HIV, hepatitis B (HBV) or hepatitis C (HCV). A
positive HBV surface antigen (HBsAg) test at screening excludes a subject.

12. Presence of current or a history of ongoing, chronic or recurrent
infections or infectious disease. Exception for plantar warts and
onychomycosis.

13. Autoimmune disease such as multiple sclerosis, inflammatory bowel disease,
rheumatoid arthritis or other immune-inflammatory diseases.*

14. Hypersensitivity for dermatological marker at screening.

15. Current smoker and/or regular user of other nicotine-containing products
(e.g., patches).

16. History of or current drug or substance abuse considered significant by the
PI (or medically qualified designee), including a positive urine drug screen.

17. Use of any prescription or OTC medications within 7 days or 5 half-lives
(whichever is longer) prior to LPS administration, unless, in the opinion of
the Investigator, the medication will not interfere with the study procedures
or compromise safety. Exception for prescription contraceptives and paracetamol
in case of local pain.*

18. Use of any vitamin, mineral, herbal, and dietary supplements within 7 days
prior to LPS administration(s), or within less than 5 half-lives (whichever is
longer), until the follow-up visit.;

19. Any vaccination within the last 4 weeks before day 1 or intention to
receive any vaccination(s) before the last day of follow-up.

20. Person of childbearing potential who is pregnant, breast-feeding, or
planning to become pregnant during the study.**

21. Prolonged exposure of the investigational skin (back) to sunlight
(including artificial tanning) from three weeks prior to the study until EOS.