SAD/MAD Safety and PK Study of RBN-3143 in Healthy and Atopic Dermatitis Subjects

• Status: Not yet recruiting
• Trial end date: 2023-06-30
• Target enrollment: 0
• Participant gender: All

Summary

RBN-3143 Background: PARP proteins are members of a family of seventeen ADP-ribosyltransferase (ART) enzymes that regulate cellular processes including gene expression, protein degradation, and multiple cellular stress responses. RBN-3143 is a PARP-14 inhibitor. PARP14 is over-expressed in tissues with inflammatory diseases. RBN-3143 is a novel, orally administered PARP14 inhibitor that was developed to be evaluated as therapy for a range of inflammatory diseases, with an initial focus on Atopic Dermatitis.

Study Overview: The study consists of 2 parts. Part A: This part of the study will be conducted in a clinical research unit (CRU) and will enroll healthy adult subjects to determine the safety of RBN-3143; its absorption, metabolism, and excretion (what the body does to this drug); and will assess its potential pharmacodynamic properties (what the drug does to the body).

There are 3 subsections to this part of the study. The first segment will be conducted in a double-blind manner (neither the investigator nor subject will know if placebo or RBN-3143is given) and will assess RBN-3143 when taken in a fasted state (before food) as either a single dose or twice daily dose. The last two segments will be Open Label (all subjects will receive RBN-3143) and will assess RBN-3143 when taken with food, with pantoprazole (optionally), a medication that decreases the amount of acid in the stomach, and with midazolam

Part B: After completion of Part A, the second part of the study will be conducted in patients with moderate to severe atopic dermatitis and Part B details will be included at that time.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Ribon Therapeutics, Inc.

Criteria

Inclusion Criteria:

1. Healthy male or female subjects between 18 and 55 years of age (inclusive at the time of informed consent) (Part A subjects only)

2. Body mass index (BMI) between ≥18 and ≤30 kg/m2 (inclusive) at Screening

3. Good general health, with no significant medical history, have no clinically significant abnormalities on physical examination at Screening and/or before administration of the initial dose of study drug

4. Clinical laboratory values within normal range as specified by the testing laboratory, unless deemed not clinically significant by the Investigator

5. Willingness and ability to speak, read, and understand English, and provide written informed consent

6. Must be a non-smoker or former smoker. Subjects must have negative cotinine results in drug tests at Screening and Baseline

7. Females must be:

Non-pregnant Non-lactating Must use a non-hormonal, acceptable, highly effective double contraception from Screening until study completion, including the Follow-up Period

Acceptable non-hormonal double contraception is defined as a condom AND one other form of the following:

• An IUD (non-hormonal)

• Documented evidence of surgical sterilization at least 6 months prior to Screening (eg, tubal occlusion, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy for women or vasectomy for men [with appropriate post-vasectomy documentation of the absence of sperm in semen] provided the male partner is a sole partner)

WOCBP must have:

A negative pregnancy test at Screening and Day 1 and be willing to have additional pregnancy tests as required throughout the study

Post-menopausal Women:

Women not of childbearing potential must be:

Postmenopausal for ≥12 months Postmenopausal status will be confirmed through testing of FSH levels ≥ 40 IU/L at Screening for amenorrhoeic female subjects

Abstinence:

Females who are abstinent from heterosexual intercourse will also be eligible. Complete abstinence by the subject for the duration of the study and for 1 month after the last study treatment is acceptable.

Note: Periodic abstinence (eg, calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not considered highly effective methods of birth control.

Female subjects who are in same-sex relationships are not required to use contraception.

Males:

If engaged in sexual relations with a WOCBP:

The subject and his partner must be surgically sterile (eg, >30 days since vasectomy with no viable sperm, tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy)

Must use an acceptable, highly effective contraceptive method from Screening until study completion, including the Follow-up Period. Acceptable methods of contraception include the use of condoms and the use of an effective contraceptive for the female partner that includes:

• OCPs

• Long acting implantable hormones

• Injectable hormones

• Vaginal ring

• Use of an IUD Subjects with same-sex partners (abstinence from penile-vaginal intercourse) are eligible

8. For at least 90 days after the last dose of study drug, male subjects must not donate sperm and female subjects must not donate ovum

9. Willingness and ability to remain at the study site unit for the duration of the confinement period and return for the outpatient visit/s defined in the protocol and comply with all testing and requirements defined in the protocol, including all PK blood sampling.

Exclusion Criteria:

1. Any clinically significant and relevant deviations from normal in physical examination, electrocardiogram (ECG), or clinical laboratory tests, as evaluated by the Investigator or delegate

2. An illness within 30 days of Screening considered clinically significant by the Investigator

3. Prior or ongoing medical conditions, physical findings, laboratory abnormality or a history of neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease that is considered as significant by the Investigator or delegate, and in the Investigator's opinion, could adversely affect the safety of the subject

4. Abnormal ECG findings at Screening that are considered by the Investigator to be clinically significant:

1. Significant history of cardiovascular disease

2. ECG results showing QTcF >450 msec

3. Elevation of blood pressure (BP), i.e., supine systolic BP >140 mmHg and/or diastolic BP >90 mmHg, or heart rate >100 beats per minute at rest

5. Use of any prescription medication within 14 days of dosing or over-the-counter (OTC) medication (including vitamins) within 48 hours of dosing or intends to use any prescription medication or OTC medication during the study that may interfere with the evaluation of study medication. Simple analgesia (paracetamol, nonsteroidal anti-inflammatory drug [NSAID]) may be permitted

6. Ingestion of herbal medicines within 3 weeks before Screening, and grapefruit, grapefruit juice, star fruit or orange marmalade (made with Seville oranges) within 2 weeks prior to dosing, or intends to use any of these products during the study

7. Subjects must have no relevant dietary restrictions and be willing to consume standard meals provided

8. Consumption of alcohol, caffeine or xanthine-containing products 48 hours before dosing or intends to use any of these products during the study period

9. A history of substance abuse or dependency or history of recreational intravenous (IV) drug use over the last 5 years

10. A positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV) antibody, or COVID-19 (if conducted, at the Investigator's discretion) at Screening

11. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the Follow-up Period

12. Use of any investigational product (IP) or investigational medical device within 30 days prior to Screening, or 5 half-lives of the product (whichever is the longest) or participation in more than 4 investigational drug studies within 1 year prior to Screening

13. Donated or lost a significant volume of blood (>450 mL) within 4 weeks prior to the first study drug administration

14. Unwilling to reside in the study unit for the duration of the study or to cooperate fully with the Investigator, delegate or site personnel.

15. 15. Alkaline phosphatase (ALP), aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >1.5 × upper limit of normal at Screening. Repeat testing at Screening is acceptable for out-of-range values following approval by the Investigator or delegate

16. Estimated Glomerular Filtration Rate (eGFR) < 90 mL/min/1.73m2

17. Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the subject will comply with the protocol or complete the study per protocol

18. Plasma donation within 7 days prior to the first study drug administration

19. Fever (temperature >38°C) or symptomatic viral or bacterial infection within 2 weeks prior to Screening

20. History of severe allergic or anaphylactic reactions to medicines or vaccines

21. History of malignancy, except for non-melanoma skin cancer, excised more than 2 years ago and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to Screening

22. History or presence of a condition associated with significant immunosuppression

23. History of life-threatening infection (eg meningitis)

24. Infections requiring parenteral antibiotics within the 6 months prior to Screening

25. For the Food effect cohort only: a diet that in the opinion of the Investigator is incompatible with the on-study diet (e.g. lactose intolerance diet)

26. Unwilling to refrain from strenuous exercise within 48 hours prior to visits and during confinement at the CRU