First-in-Human Study of Oral SDC-1801 in Healthy Adults and Adults with Plaque Psoriasis (Parts 1 and 2)
A First-in-human, Phase I, Randomised, 4-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Food Effects, and Pharmacodynamics of Single Ascending and Multiple Ascending Oral Doses of SDC-1801 in Healthy Adults or Adults with Plaque Psoriasis (Parts 1 and 2 - Healthy Adults - SAD & MAD)
Pharmaceutical Solutions Australia Pty Ltd
80 participants
Jun 5, 2023
Interventional
Conditions
Summary
SDC-1801 is a small molecule tyrosine kinase 2 (TYK2)/janus kinase 1 (JAK1) inhibitor entering clinical development for the treatment of participants with inflammatory diseases such as psoriasis. The nonclinical good laboratory practice (GLP) toxicology and safety pharmacology studies indicate that it is appropriate to cautiously assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SDC-1801 in the context of a well-designed, first-in-human (FIH) study. It is reasonable to say that the risk of adverse events (AEs) for JAK inhibitors are broadly similar to those for other biological disease modifying antirheumatic drug (bDMARD) classes. However, concealed within this, there are also important differences between JAK inhibitors and bDMARDs. Tofacitinib and baricitinib have AE profile characteristics that distinguish them from the other bDMARD classes, with signals including an increased risk of herpes zoster reactivation, elevation in lipids, and decreases in haemoglobin and lymphocytes (including natural killer cells). Based on available nonclinical data, SDC-1801 is a potent and selective small molecule TYK2/JAK1 inhibitor currently in development for inflammatory and autoimmune indications, and it has the potential to have an improved safety profile and similar efficacy profile compared with other JAK inhibitors and specific TYK2 inhibitors. A randomised, placebo controlled, dose-escalation, sequential group design is regarded as an appropriate standard design to initiate the cautious assessment of safety, tolerability, and PK of a new investigational product in healthy volunteers. The chosen sample sizes will provide sufficient data to make an initial assessment of the safety, tolerability, and PK of SDC-1801.
Eligibility
Inclusion Criteria14
- Participants are eligible to be included in the study only if all of the following criteria apply:
- Able and willing to comply with the protocol requirements and to sign the informed consent form (ICF) prior to any screening evaluations.
- Healthy males and females between 18-55 years of age on date of signing ICF.
- Body mass index (BMI) between 18-32 kg/m2, inclusive.
- Participants in good health based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and fasting clinical laboratory safety tests as determined by the Investigator.
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and
- alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) values less than or equal to 1.3 x upper limit of normal (ULN). Total bilirubin less than or equal to 1.3 x ULN; participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is less than or equal to ULN.
- Participant must be able and willing to comply with restrictions on prior and concomitant medication.
- Negative for severe acute respiratory syndrome coronavirus-2 infection.
- Non-smoker and not using any nicotine-containing products
- Negative screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone, tricyclic antidepressants) and alcohol.
- Must agree to avoid prolonged exposure to the sun and avoid other ultraviolet light sources (e.g. tanning beds) during the study period and for 7 days after the last dose of study drug.
- Adherence to effective contraception or are proven post-menopausal
- No evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) or history of untreated or inadequately treated latent or active TB infection
Exclusion Criteria38
- Known hypersensitivity to investigational medicinal product (IMP) ingredients or history of
- a significant allergic reaction to IMP ingredients as determined by the Investigator
- Positive serology for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV),
- or history of hepatitis from any cause with the exception of hepatitis A
- History of or a current immunosuppressive condition (e.g. human immunodeficiency virus
- [HIV] infection).
- Having any illness, judged by the Investigator as clinically significant, in the 3 months prior to the first dose of study drug.
- Current clinically significant infection or clinically significant infection within 6 months of
- first dose of study drug
- History of chronic or recurrent infectious disease within the last 2 years.
- Symptomatic herpes zoster or herpes simplex within 12 weeks of first dose of study drug, or more than one episode of local herpes zoster, or a history of disseminated zoster.
- Pregnant or breast feeding participants.
- Presence or sequelae of gastrointestinal, liver, or kidney (estimated creatinine clearance
- less than or equal to 80 mL/min, using the Cockcroft-Gault formula; if calculated creatinine clearance is less than or equal to 80mL/min a 24-hour urine collection may be performed to assess renal function) disease,
- History of malignancy within the past 5 years (except for basal cell carcinoma of the skin
- that has been treated and with no evidence of recurrence)
- Clinically significant abnormalities detected on 12-lead ECG
- Clinically significant abnormalities detected on vital signs.
- Significant blood loss (including blood donation [>500 mL]), or transfusion of any blood
- product within 12 weeks prior to Screening.
- Treatment with any drug known to have a potential for major organ toxicity in the last
- months before the first dose of this study drug.
- Treatment with any medication (including over-the-counter and/or prescription medicines [including hormonal replacement therapy for postmenopausal participants], dietary supplements, nutraceuticals, recreational drugs, vitamins and/or herbal supplements) within the last 2 weeks or 5 half-lives of that drug (whichever is longer) prior to the first dose of this study drug. Occasional paracetamol (maximum dose of 2 g/day and 10 g/2 weeks) is permitted for use at any time during the study.
- Vaccination with live virus, attenuated live virus, or any live viral components within the
- weeks prior to the first dose of study drug or is to receive these vaccines during study
- treatment or within 8 weeks following completion of study treatment.
- Routine household contact (during study treatment or for 8 weeks following completion of study treatment) with individuals who have received vaccination with live virus or
- attenuated live virus.
- Active drug or alcohol abuse
- Consumption of a large quantity of caffeinated coffee or tea (>6 cups per day) or equivalent.
- Consumption of grapefruit, grapefruit juice, or citrus fruits within 7 days prior to the first dose of study drug and until collection of the final PK blood sample.
- Current or previous participation in another investigational research study where the
- participant has received a drug, drug/device, or biologic within 12 weeks or 5 of its
- half-lives (whichever is longer) prior to the first dose of this study drug.
- Investigator or other study site staff who is directly involved in the conduct of the study and their relatives.
- Any condition or circumstances that in the opinion of the Investigator may make a
- participant unlikely or unable to complete the study or comply with study procedures and
- requirements.
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
A randomised, placebo controlled, dose-escalation, sequential group design is regarded as an appropriate standard design to initiate the cautious assessment of safety, tolerability, and PK of a new investigational product in healthy volunteers or adults with psoriasis. In Parts 1 and 2 of the study, a double-blind design is used to eliminate reporting bias and to assist in the reported evaluation of TEAEs. Placebo is considered an appropriate control in the absence of an approved, active comparator with a mechanism of action comparable to that of SDC-1801, and in the likely absence of any sustained clinical response from the brief 14 days’ dosing with SDC-1801. The study will be conducted in a single centre in Australia for Parts 1 and 2. Parts 1 and 2 of the study consist of: - A Screening Period 2-28 days prior to randomisation to ensure participants meet the inclusion/exclusion criteria - A Study Period which include randomisation, study drug administration, and various assessments. The Study Period will begin 1 day prior to administration of the first dose of study drug. - Follow-up conducted 14 ± 3 days after administration of the final dose of study drug. GastroPlus® was used to predict the clearance of SDC-1801 in humans, which was predicted to be low, resulting in a predicted t½ of 17.1 hours. Part 1, Single Ascending Dose of SDC-1801 in Healthy Adults. A randomised, double-blind design, 3:1 ratio to a single dose of SDC-1801 or matching placebo administered as an oral capsule/s and consist of at least 6 sequential, ascending dose cohorts (Cohorts A, B, C, D, E, and F). The participants in each cohort in Part 1 will be randomised in a 3:1 ratio to a single dose of SDC-1801 or matching placebo. SDC-1801 or placebo will be administered as an oral capsule/s after a fast of at least 8 hours. A sentinel dosing approach will be applied for each cohort whereby, initially, only 2 participants (1 for SDC-1801 and 1 for placebo) will be dosed on Study Day 1. On Study Day 2, if the review by the Principal Investigator and the Sponsor’s Medical Monitor of vital signs, TEAEs, and 24-hour post-dose laboratory safety data for the sentinel participants is satisfactory, then the remaining 6 participants in the cohort will start dosing the next day. Post dosing, an oral examination will be performed to ensure all capsules have been swallowed by the participants. Each cohort will consist of 8 healthy adults (a total of 48 participants). The planned dose escalation sequence for SDC-1801/placebo in Part 1 is shown below: Cohort A: starting dose = 5 mg Cohort B: a dose not to exceed 10 mg Cohort C: a dose not to exceed 30 mg Cohort D: a dose not to exceed 75 mg Cohort E: a dose not to exceed 150 mg Cohort F: a dose not to exceed 300 mg. Participants will be confined at the investigation site from Day -1 to approximately 120 hours after dosing (i.e. Day 6). A follow-up visit will take place 14 ± 3 days after the administration of study drug. Each participant will be in the study for approximately 6 weeks (Screening Visit to Follow-up Visit) and will receive 1 dose of SDC-1801 or placebo. Part 2, Multiple Ascending Doses of SDC-1801 in Healthy Adults. Part 2 will be randomised in a 3:1 ratio, double-blind design, and consist of at least 4 sequential, ascending dose of SDC-1801 or matching placebo cohorts (Cohorts A, B, C and D) administered as an oral capsule/s once daily (OD) or twice daily (BID) for 10 days. Participants who have been enrolled in Part 1 of the study will not be allowed to participate in Parts 2 & 3 of the study. Cohort A in Part 2 will only start after the Safety Review Committee (SRC) has taken place to review the available safety, tolerability, and PK data from Cohorts A, B, and C in Part 1, and members of the SRC have decided that it is appropriate to initiate Part 2 of the study and the dose that should be used for Cohort A in Part 2. The study drug will be administered after an overnight fast of at least 8 hours and if a BID dose regimen is chosen, the second dose will be administered at approximately 8pm following a 4-hour fast. Post dosing, an oral examination will be performed to ensure all capsules have been swallowed by the participants. Each cohort will consist of 8 healthy adults (a total of 32 participants). In Part 2, a sentinel dosing approach will be applied for each cohort whereby, initially, only 2 participants (1 for SDC-1801 and 1 for placebo) will be dosed on Study Day 1. On Study Day 2, if the review by the Principal Investigator and the Sponsor's Medical Monitor of vital signs, TEAEs, and 24-hour post-dose laboratory safety data for the sentinel participants is satisfactory, then the remaining 6 participants in the cohort will start dosing the next day. The starting dose of SDC-1801/placebo for cohort A in Part 2 will not exceed a daily dose of 75 mg. Dose selection for Cohorts B, C and D in Part 2 will be based on a review of all emergent safety, tolerability, and PK data from the preceding cohort(s). Each participant will be in the study for approximately 8 weeks and will receive a maximum of 10 or 19 doses of SDC-1801 or placebo. The participants in each cohort will be randomised in a 3:1 ratio to multiple doses of SDC-1801 or matching placebo. SDC-1801 or placebo will be administered as an oral capsule/s once daily (OD) or twice daily (BID) for 10 days, based on the emergent safety and PK results from Part 1 of the study. On Day 1 and Day10 (to minimise any effect of food on PK assessments), the study drug will be administered after an overnight fast of at least 8 hours and if a BID dose regimen is chosen, the second dose will be administered at approximately 8pm following a 4-hour fast. Between each dose cohort, a blinded analysis of safety, tolerability, and PK will be performed. If the dose for a cohort is judged to be safe by the SRC, then 7 days after completion of dosing in that cohort, dosing of the next cohort can begin. The participants will be confined to the Clinical Pharmacology Unit (CPU) from mid-afternoon or evening of Day -1 to approximately 120 hours after the final dose of study drug (i.e. Day 15). A follow-up visit will take place 14 ± 3 days after administration of the final dose of study drug. Between each dose cohort, a blinded analysis of safety, tolerability, and PK (up to 24 hours post-dose) will be performed. If the dose for a cohort is judged to be safe by the SRC, then 7 days after completion of dosing in that cohort, dosing of the sentinel participants in the next cohort can begin.
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12623000416695