A First-In-Human Study to Evaluate the Safety, Tolerability, and Efficacy of Si-544 in Adults With Atopic Dermatitis

This is a multi-center, Phase 1b, double-blind, placebo-controlled, SAD and MAD, first-in-human study in subjects with mild to severe AD receiving si-544. The study consists of 2 parts, an SAD and an MAD part. In both parts, subjects will be treated in cohorts and will be randomized within each cohort to treatment with si-544 or placebo. Initially, 2 sentinel subjects will be treated (randomized to placebo or si-544) in each cohort.


Eligibility Criteria:
SAD and MAD part

1. Subject has the capacity for consenting, was informed about the nature, the scope, and the relevance of the clinical study, voluntarily agrees in participation and in the study provisions, and duly signed the informed consent form approved by the ethics committee before any study-related procedure.
2. Men and women aged ≥18 to 75 years
3. Willing and able to adhere to the protocol requirements
4. {deleted}
5. Women of childbearing potential must:

   1. have a negative pregnancy test (blood) at Screening.
   2. agree to use, and be able to comply with, highly effective measures of contraceptive control (failure rate less than 1% per year when used consistently and correctly) without interruption, from Screening through 30 days after the last IMP treatment.

   Reliable methods for this study are:

   i. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) ii. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) iii. intrauterine device iv. intrauterine hormone-releasing system v. bilateral tubal occlusion vi. vasectomized sexual partner (provided that the partner is the sole sexual partner of the woman of childbearing potential and has received medical assessment of the surgical success) vii. sexual abstinence (only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment) Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the subject (periodic abstinence \[eg, calendar, ovulation, symptothermal, postovulation methods and withdrawal\] is not an acceptable method of contraception).

   c. agree to abstain from breast feeding during the study participation and for 90 days after the last IMP treatment.

   Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile women (tubal ligation, hysterectomy, or bilateral oophorectomy) may be enrolled.
6. Men must practice true abstinence or agree to use a condom during sexual contact with a pregnant woman or a woman of childbearing potential for at least 90 days after the last IMP treatment, even after undergoing a successful vasectomy.

   SAD part only
7. Clinical diagnosis of mild to severe AD

   MAD part only
8. Clinical diagnosis of mild to severe AD with a SCORAD ≥15

Exclusion Criteria:

SAD and MAD part

1. Change (ie, starting anew, change in frequency, or change in drug substance) in standard systemic and topical therapy, or in immunosuppressive drug therapy within 4 weeks before Screening (for biologics such as dupilumab, the therapy may not be changed within 12 weeks before Screening), as judged by the investigator
2. Known history of hypersensitivity to constituents or excipients in the pharmaceutical formulation of the IMP
3. Uncontrolled hypertension or uncontrolled diabetes
4. History of seizures
5. Presence or history of paresthesia or neuropathy
6. Clinically significant ECG abnormalities, as judged by the investigator
7. Clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, renal, or other major systemic disease, as judged by the investigator
8. Presence of acute infection within 7 days before Screening, as judged by the investigator
9. Known or active infection with Mycobacterium tuberculosis
10. Known or active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
11. Vaccination within 2 weeks before Screening and/or planned vaccination during the SAD part or the treatment period of the MAD part
12. Pregnancy
13. Any finding or medical condition prohibiting the inclusion in the study, as judged by the investigator
14. Current or previous (within 4 weeks before Screening) participation in another clinical study with an investigational medicinal product or medical device
15. Known or suspected abuse of alcohol, drugs, or medicinal products
16. Employee of the sponsor, or employee, or relative of the investigator
17. Use of prohibited medication
18. Subjects committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
19. Legal incapacity or limited legal capacity

    MAD part
20. Previous participation in the SAD part of this study with IMP dosing within 3 months before the planned first dosing of the MAD part.