None listed
Conditions
Brief summary
The purpose of this study is to test the safety and tolerability of a new medication (called FTP-637) in healthy volunteers. FTP-637, an investigational drug, is a small molecule inhibitor of tyrosine kinase 2 (TYK2) being developed for the treatment of psoriasis and other autoimmune diseases. The study will consist of 2 parts; Part A - multi-cohort Single Ascending Dose (SAD), and Part B – multi-cohort Multiple Ascending Dose (MAD).
Interventions
FTP-637 will be supplied to participants as a solution for oral administration daily. FTP-
637, an investigational drug, is a small molecule inhibitor of tyrosine kinase 2 (TYK2) being developed for the treatment of psoriasis and other autoimmune diseases.
Part A SAD:
Enrolled participants will be assigned to one of Cohort 1, 2, 3, 4, 5 or 6 will receive a single dose of FTP-637 solution (or placebo) between the dose levels; 5 to 150mg. Participants will be dosed in the morning following an ove
FTP-637 will be supplied to participants as a solution for oral administration daily. FTP- 637, an investigational drug, is a small molecule inhibitor of tyrosine kinase 2 (TYK2) being developed for the treatment of psoriasis and other autoimmune diseases. Part A SAD: Enrolled participants will be assigned to one of Cohort 1, 2, 3, 4, 5 or 6 will receive a single dose of FTP-637 solution (or placebo) between the dose levels; 5 to 150mg. Participants will be dosed in the morning following an overnight fast of 10 hours, and will continue to fast for a further 4 hours post dose. Participants will also fast from water 1 hour prior until 1 hour post dose. Food effect, cohort 11, receive open label FTP-637 (no placebo) on 2 occasions, once fasted once fed. Fed means that you will be required to fast overnight, and then eat a high calorie meal within 30 minutes and FTP-637 is administered at the end of the meal. Fasted means that you will fast overnight before FTP-637 is administered. The 2 dosing occasions will be separated by 5 days. The dose used will be decided by the Safety Review Committee after reviewing the safety and tolerability data of the previous SAD cohorts. The high calorie meal should contain 800 to 1000 Calories (approximately 150 Calories from protein, 250 Calories from carbohydrates and 500 to 600 Calories from fat. An example of a high calorie breakfast consists of • Two eggs fried in butter • Two strips of bacon • Two slices of toast with butter • 110 g of hash brown potatoes • 240 mL of whole milk. Part B MAD: Enrolled participants will be assigned to one of Cohort 7, 8, 9, 10 will receive a 7 doses of FTP-637 solution (or placebo) once / twice daily for 7 days. The dose level of dosing for each Cohort is to be selected based on Part A data. Dose levels to be evaluated will be in the range of 5 to 150 mg. Part B participants will be dosed with a meal, preferably at the end of the meal but it may occur during the meal to remain within the required dosing interval. The morning dose will be administered with breakfast. In case of twice daily dosing, the PM dose will be administered with a snack. Water is not restricted at any time. The breakfast will consist of a standard breakfast, and the snack will have a caloric and fat content is similar (±30%) to that of the breakfast. The frequency of dosing will be decided by the Safety Review Committee after reviewing the safety and tolerability data of the previous MAD cohorts.
Sponsors
Alumis Inc (formerly Esker Therapeutics, Inc)
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
- Body mass index greater than or equal to 18.0 and less than or equal to 32.0 kg/m2, with a body weight greater than or equal to 50 kg at screening. - Be nonsmokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration and have a negative test for cotinine at the Screening visit and at check-in on Day -1. - Medically healthy without clinically significant abnormalities at the screening visit, at check-in on Day -1 and pre-dose on Day 1 - Conventional 12-lead ECG recording in triplicate consistent with normal cardiac conduction and function
Exclusion criteria
- History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically relevant. - Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications. - Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma). - Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia. - Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration. - Presence or evidence of recent sunburn, scar tissue, tattoo (more than 25% of body area), open sore, or branding that, in the opinion of the Investigator, would interfere with interpretation of skin adverse reaction assessments. - Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase [GGT], bilirubin (total, conjugated and unconjugated) or alkaline phosphatase (ALP) or elevated 2.0-fold above ULN for aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Participants with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants. - Positive test results for active human immunodeficiency virus (HIV-1 and HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit. - History of active, latent or inadequately treated tuberculosis infection. - Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. Exception: cholecystectomy is allowed. - Estimated creatinine clearance (CrCl) < 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN. - History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc./Vol], 100 mL wine [12% Alc./Vol], 30 mL spirit [40% Alc./Vol]) during less than or equal to 12 months prior to the screening visit. - Positive drug or alcohol test results at the screening visit or at check-in (Day -1) (may be repeated once, if a positive test was recorded in the first instance, at the discretion of the PI). - Use of any systemically absorbed prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, except occasional use of paracetamol (up to a maximum of 4 doses per day of 500-mg paracetamol, and no more than 3g per week). - Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial. - Known hypersensitivity to any of the study drug ingredients. - Known hypersensitivity to interferon alfa or any component of the product (Part B only). - Use of any vaccinations within 30 days prior to the first study drug administration. - Participation in another investigational clinical trial within 60 days (or 5 half-lives, of the investigational agent) (whichever is longer) prior to the first study drug administration. - Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.
Outcome results
None listed