Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the complement inhibitor AMY-101. A prospective, single-center, open-label, First-In-Human (FIH) clinical study in healthy male volunteers.

AMYNDAS is developing a novel peptidic complement inhibitor AMY-101, based on the third-generation compstatin analogue Cp40. AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the central "functional hub" that controls the upstream activation/amplification and downstream effector functions of complement. By binding to C3, AMY-101 inhibits the cleavage of native C3 to its active fragments C3a and C3b. As a consequence, the deposition of C3b, amplification via the alternative pathway and all downstream complement responses are prevented. AMY-101 is being developed to treat complement-mediated diseases, which are largely driven by aberrant C3 activation.

This first-in-human study of the C3-targeting complement inhibitor AMY-101 investigates the safety and PK/PD profile of AMY-101 in healthy male volunteers after Single Ascending Dose (SAD) and Multiple Doses (MD) using subcutaneous (SQ) or intravenous (IV) administration. The study is a prospective, single-center, open-label evaluation in healthy male volunteers.

Inclusion Criteria:

1. Willing and able to give written informed consent for participation in the study.
2. Healthy male subject aged 18-60 years, inclusive at the time of signing the informed consent.
3. Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m2 and weight at least 50 kg.
4. Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
5. Willing to use condom and contraceptive methods with a failure rate of < 1% to prevent pregnancy and drug exposure of a partner and to refrain from donating sperm from the date of dosing until three (3) months after dosing of the IMP.
6. Willing and able to complete all procedures according to the Protocol.

Exclusion Criteria:

1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.

2. History of any Neisseria meningitidis infection

3. History of unexplained, recurrent infection, or infection requiring treatment with systemic antibiotics within the last 60 days prior to dosing.

4. History of latent or active tuberculosis, as assessed by the investigator based on chest X-ray and positive Quantiferon-TB Gold test.

5. History of complement deficiency.

6. History of any type of malignancy. However, completely resolved minor malignancies, at the discretion of the Investigator, may not be an exclusion criterion (for example: Non-Melanoma Skin Cancer).

7. Diagnosis of autoimmune, immunologic or rheumatologic disease (eg, systemic lupus erythematosus, rheumatoid arthritis).

8. Any clinically significant illness, medical/surgical procedure or trauma within four (4) weeks of the administration of IMP.

9. High CRP at screening (> 0.5 mg/dL).

10. Current evidence or history of bacterial, viral or fungal infection within 14 days prior to (first) dosing or longer according to the judgment of the investigator for e.g. viral infections including herpes simplex or herpes zoster.

11. Any current condition or risk, which, in the opinion of the Investigator, may interfere with the subject's participation in the study, poses an added risk for the subject, or confounds the assessment of the subject or outcome of the study

12. Any clinically significant abnormality in clinical chemistry, hematology, or urinalysis results at the time of screening, as judged by the Investigator.

13. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and/or Human Immunodeficiency Virus (HIV).

14. After 10 minutes supine rest abnormal vital signs defined as any of the following:

    • Systolic BP > 140 mm Hg
    • Diastolic BP > 95 mm Hg
    • HR < 40 or > 90 beats per minute

15. Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormality in the resting ECG, as judged by the Investigator.

16. Any history of any allergy/hypersensitivity or anaphylactic reaction or on-going allergy/hypersensitivity. History of hypersensitivity to antibiotics or drugs with a similar chemical structure or class to AMY-101.

17. Use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals within two (2) weeks prior to the administration of IMP, except the occasional intake of paracetamol/acetominophen (maximum 2000 mg/day; and not exceeding 3000 mg/week) or nasal decongestant without cortisone or antihistamine, at the discretion of the Investigator.

18. Administration of another new chemical entity (defined as a compound that has not been approved for marketing) or having participated in any other clinical study that included drug treatment within 30 day or 5 half lives of the last administration of the other IMP. Subjects consented and screened but not dosed in previous phase I studies are not excluded.

19. Immunization with a live-attenuated vaccine one (1) month prior to the first administration of IMP.

20. Current smokers or users of nicotine products. Irregular use of nicotine (e.g. smoking, snuffing, chewing tobacco) less than three (3) times per week is allowed before screening visit.

21. History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.

22. Positive screen for drugs of abuse at screening or on admission to the unit or positive screen for alcohol at screening or on admission to the unit prior to administration of the IMP.

23. Use of anabolic steroids.

24. Plasma donation within one (1) month of screening or any blood donation/blood loss > 450 mL during the three (3) months prior to screening.

25. Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.