Inflammatory disorders Chronic spontaneous urticaria Rheumatoid arthritis
Conditions
Interventions
AS-0871
Placebo
Sponsors
Carna Biosciences, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Must have signed an ICF prior to screening, indicating that he/she understands the purpose of, and procedures required for, the trial, and indicating that he/she is willing to participate in the trial. 2. Healthy males or females of non-childbearing potential, between 18 and 64 years of age, inclusive, at screening. 3. Body Mass Index (BMI) between 18.0 and 30.0 kg/m2, inclusive, at screening. 4. Good physical and mental health as established by medical history, physical examination, ECG, and vital signs (including temporal body temperature) recording, and results of biochemistry, haematology, and urinalysis tests during screening as judged by the investigator. 5. Non-smoker/non-user of nicotine-containing products for at least 3 months prior to screening, to be confirmed by a urine cotinine dipstick test at screening and on Day -1 of the first treatment period of each cohort. 6. Availability and willingness to complete the trial and follow the instructions of the investigator or trial-site personnel. 7. Willing and able to adhere to the prohibitions and restrictions specified in the protocol. 8. Easy venous accessibility. 9. During the trial (from the day of first trial medication onwards) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after the last trial medication intake, a male subject must agree: to wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male subject should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak); not to donate sperm for the purpose of reproduction. Contraceptive use should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical trials. 10. At screening, a female subject must be not of childbearing potential defined as: postmenopausal A postmenopausal state is defined as no menses for > 12 months without an alternative medical explanation. A high follicle stimulating hormone (FSH) level (> 40 IU/L or mIU/mL) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormone replacement therapy. In the absence of > 12 months of amenorrhea, 2 FSH measurements have to be available, measured at least 3 months apart, or permanently sterile Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy. 11. Female subject, except if postmenopausal, must have a negative highly sensitive serum (*-human chorionic gonadotropin [*-hCG]) pregnancy test at screening and female subject must have a negative urine pregnancy test on Day -1 of the first treatment period of each cohort. 12. Female subject must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial and for at least 90 days after the last trial medication intake in the last treatment period. 13. Able to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the trial.
Exclusion criteria
Exclusion criteria: 1. History of or current clinically significant medical illness including (but not limited to) gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, endocrinologic, genitourinary, renal, hepatic, respiratory, inflammatory, neoplastic, haematologic, or infectious disease, or any other illness that the investigator considers should exclude the subject or that could interfere with the interpretation of the trial results. 2. Clinically relevant abnormal values for haematology, biochemistry, or urinalysis at screening or on Day -1 of the first treatment period, as judged by the investigator. 3. Values of hepatic aminotransferase (ALT and/or AST) > 1.5 × the upper limit of normal range (ULN) at screening or on Day -1 of the first treatment period. 4. Values of GGT and/or ALP > 1.25 x ULN at screening or on Day -1 of the first treatment period. 5. Values of total cholesterol > ULN and LDL cholesterol > 1.25 x ULN at screening or on Day -1 of the first treatment period. 6. Values of total bilirubin > ULN at screening or on Day -1 of the first treatment period. 7. Values of urea >1.5 × ULN at screening or on Day -1 of the first treatment period. 8. A QTcF > 450 ms for male subjects and > 470 ms for female subjects. 9. Clinically significant abnormal complete physical examination at screening or on Day -1 of the first treatment period, or clinically significant abnormal symptom-driven physical examination at predose on Day 1 of the first treatment period (if applicable), or clinically significant abnormal values for vital signs (including temporal body temperature) or 12-lead ECG at screening or at predose on Day 1 of the first treatment period, as judged by the investigator. 10. Clinically significant presence or history of allergy or intolerance (including lactose) as judged by the investigator. 11. Previously demonstrated clinically significant allergy or hypersensitivity to any of the components of the trial medication (see IB8). 12. Positive serology for hepatitis A virus (HAV) immunoglobulin M (IgM), hepatitis B virus surface antigen (HBsAg), anti-hepatitis C virus antibodies (anti-HCV-AB), or anti human immunodeficiency virus antibodies 1 + 2 (anti-HIV-AB 1 + 2) at screening. 13. History of alcohol or drug abuse within the last 2 years before screening or positive test result(s) for alcohol and/or drugs of abuse at screening or on Day *1 of the first treatment period of each cohort. Note: A positive alcohol and/or drug test may be repeated once (as soon as possible and within the screening period) to exclude a technical error. Subjects with a negative alcohol and/or drug test at retest may be included. 14. Regular alcohol consumption > 14 units per week (1 unit = a 200-mL glass of average-strength beer, 25 mL of 40% spirit. A 125-mL glass of wine is 1.5 unit). 15. A history of cancer excluding carcinoma in situ or intra-mucosal cancer. 16. Surgery of gastro-intestinal tract that might interfere with absorption (subjects who have had cholecystectomy may be included). Subject has currently significant and active diarrhoea, nausea, or constipation that in the investigator*s opinion could influence drug absorption or bioavailability. 17. Intake of any disallowed therapies (see Section 5.10, Prior and Concomitant Medication) before the first trial medica
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety and tolerability assessments as per protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. PK of AS-0871 in plasma following 7 single dose oral administrations under fasted conditions; One single dose level will be tested under fed conditions to assess the food effect of AS-0871. 2. B-cell and basophil responses to anti-IgD and anti-IgE stimulation of AS-0871 in blood following single dose oral administrations 3. Potential QT effects of AS-0871 following single dose oral administations by exposure-response analysis | — |
Countries
Netherlands
Outcome results
None listed