Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000419662
Ethics application status
Approved
Date submitted
31/03/2023
Date registered
27/04/2023
Date last updated
26/05/2024
Date data sharing statement initially provided
27/04/2023
Date results information initially provided
26/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
First-in-Human Study of Oral SDC-1801 in Healthy Adults and Adults with Plaque Psoriasis (Part 3 - Food Effects)
Scientific title
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
(Part 3 - Healthy Adults - Food Effects)
Secondary ID [1] 309352 0
SDC-1801-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Plaque Psoriasis 329557 0
Condition category
Condition code
Inflammatory and Immune System 326488 326488 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part 3 of this study takes the form of a a randomised, open label, 2-way crossover study, consistent with United States (US) Food and Drug Administration (FDA) guidance on studies to investigate the effect of food on the bioavailability of investigational drugs.

Part 3, Effects of Food on SDC-1801 in Healthy Adults

Part 3 will have a randomised, open label, 2-way crossover design, and will run in parallel with Part 2 of the study. It will consist of one cohort of 16 healthy adults. Participants who have enrolled in Parts 1 or 2 of the study will not be permitted to be enrolled in Part 3 of the study.

The SDC-1801 dose to be administered will be decided by the Safety Review Committee (SRC) based upon the SDC-1801 pharmacokinetic (PK) and safety profiles observed in Part 1 of the study. The dose that is selected for Part 3 of the study will have been demonstrated to be well tolerated, and the exposure at that dose would not have exceeded that seen at the no-observed-adverse-effect-level (NOAEL) (in the most sensitive toxicology species, the dog) in Part 1 of the study.

Participants will be randomised in a 1:1 ratio to one of the following treatment sequences:

Fed, Fasted: following a fast of at least 8 hours, one single oral dose of SDC-1801 administered 30 minutes after starting a standardised breakfast (meal completed within 30 minutes), then a washout period of at least 7 days, then one single oral dose of SDC-1801 administered after a fast of at least 8 hours.

OR

Fasted, Fed: one single oral dose of SDC-1801 administered after a fast of at least 8 hours, then a washout period of at least 7 days, then (following a fast of at least 8 hours) one single oral dose of SDC-1801 administered 30 minutes after starting a standardised breakfast (meal completed within 30 minutes).

The composition of the standardised breakfast that patients will receive in the Fed condition is as follows:

Protein - 150 calories
Carbohydrate - 250 calories
Fat - 500 to 600 calories
Total Calories = 800-1000 calories

Compliance to dosing of SDC-1801 will be confirmed by examination of each participant's mouth post-dose to confirm that each capsule has been swallowed.

Participants will be administered the dose of study drug in Study Period 2 at approximately the same time as it was given in Study Period 1.

The participants will be confined to the Clinical Pharmacology Unit (CPU) for Study Period 1 (from mid-afternoon or evening of Day -1 to approximately 120 hours after the first dose of study drug [i.e. Day 6]), then they will have the 7-day washout period at home. Participants will return to the CPU for Study Period 2 and be confined there from mid-afternoon or evening of Day 14 to approximately 120 hours after the second dose of study drug (i.e. Day 20). A follow-up visit will take place 14 ± 3 days after administration of the second dose of study drug. Each participant will be in the study for approximately 9 weeks (Screening Visit to Follow-up Visit) and will receive 2 doses of SDC-1801.
Intervention code [1] 325787 0
Treatment: Drugs
Comparator / control treatment
Part 3 is an open label study, no placebo or control treatment will be administered.

Participants in Part 3, when under Fasted conditions, will be subject to an overnight fast of at least 8 hours prior to receiving their oral dose of SDC-1801. Participants are allowed to drink water during the fasting period.
Control group
Active

Outcomes
Primary outcome [1] 334331 0
In addition to the to the evaluation of the safety and tolerability of a single ascending dose (SAD) and 10 days of multiple ascending doses (MAD) of oral SDC-1801 compared with placebo in healthy adults in Parts 1 & 2, Part 3 of this study will compare the pharmacokinetics (PK) of SDC-1801 as a formulated capsule when administered in fed and fasted states to healthy adults (food effect).

Assessment of a food effect of a high-calorie, high-fat breakfast will be done by comparing data from the oral capsule/s in the fasted state with that obtained in the fed state. For the comparisons, ln-transformed PK parameters (Cmax, C24, AUC0-24, t½) of SDC-1801 will be subjected to a mixed-effects model. Point estimates of ln-transformed data for treatment Y (fed state) versus ln-transformed SDC-1801 data for treatment X (fasted state) will be calculated as the geometric mean ratio, expressed as a percentage. Treatment X will be considered as the reference treatment for the comparison.

Food effect will be evaluated by review of the 90% confidence interval obtained from the comparison of treatment Y vs treatment X.
Timepoint [1] 334331 0
To determine the food effect of a high-calorie, high-fat breakfast on the PK profile of SDC-1801, blood samples for PK analysis will be taken from participants in Part 3 of the study, in either fed, or fasted states at the following timepoints while the participants are confined in the clinical research unit.

Day 1 - at pre-dose, then at 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post -dose.
Day 2 - 24h post-dose
Day 3 - 48h post-dose
Day 4 - 72h post-dose
Day 5 - 96h post-dose
Day 6 - 120h post-dose

Participants will then be discharged from the unit for a 7 day washout period, to be conducted in their home, and return to the unit on Day 14, where after an overnight stay, they will be given a second dose of SDC-1801 in either fed or fasted states on Day 15, depending on their previous randomisation status.

PK blood samples will then be taken from participants at the following time points.

Day 15 - at pre-second dose, then at 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post-second dose.
Day 16 - 24h post-second dose
Day 17- 48h post-second dose
Day 18 - 72h post-second dose
Day 19 - 96h post-second dose
Day 20 - 120h post-second dose
Secondary outcome [1] 420823 0
Vital Signs:

Participants will have the following vital signs recorded across the study: Temperature (via a tympanic device), pulse rate (via an automated device), respiratory rate (via observation), systolic and diastolic blood pressure (via an automated device)
Timepoint [1] 420823 0
Timepoints:

Participants will have their vital signs recorded at the following timepoints:

Screening Visit (Day -28 to Day -2)
Day -1
Day 1 (at pre-dose, 2h, 4h and 12 h post-dose)
Day 2 (24h post-dose)
Day 3 (48h post-dose)
Day 4 (72h post-dose)
Day 5 (96h post-dose)
Day 6 (120h post-dose)

Following a 7 day washout, the participant will return to the clinic for a further 7 night stay in the crossover study on Day 14, where vital signs will be examined at the following time points

Day 14 (on arrival at the clinic)
Day 15 (at pre-dose, 2h, 4h and 12 h post-dose)
Day 16 (24h post-dose)
Day 17 (48h post-dose)
Day 18 (72h post-dose)
Day 19 (96h post-dose)
Day 20 (120h post-dose)

Participants will then be discharged and return to the clinic on Day 29 post-dose, where they will have their vital signs examined as part of a final follow-up visit.
Secondary outcome [2] 420824 0
ECG:

Participants will have their ECG recorded (in triplicate via a standard 12-lead ECG machine)
Timepoint [2] 420824 0
Timepoints:

ECGs will be recorded at presentation to the clinic at Screening (Days -28 to -2) and Day -1, Day 14 and at the follow-up visit on Day 29 post-dose.
Secondary outcome [3] 420825 0
Safety Laboratory Testing:

Participants will have blood and urine samples taken for blood chemistry analysis, hematology analysis & urinalysis.
Timepoint [3] 420825 0
Timepoints:

Blood and urine samples will be taken from participants at the following timepoints:

Screening Visit (Day -28 to -2)
Day 1 (pre-dose, 8 hours post-dose)
Day 2 (24 hours post-dose)
Day 4 (48 hours post-dose)
Day 6 (120 hours post-dose)
Day 14 (on presentation to the clinic)
Day 15 (pre second-dose, 8 hours post second-dose)
Day 16 (24 hours post-second dose)
Day 17 (48 hours post-second dose)
Day 20 (120 hours post-second dose)
Day 29 (final follow-up visit)

Eligibility
Key inclusion criteria
Inclusion Criteria for Part 3

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Able and willing to comply with the protocol requirements and to sign the informed consent form (ICF) prior to any screening evaluations.
2. Healthy males and females between 18-55 years of age on date of signing ICF.
3. Body mass index (BMI) between 18-32 kg/m2, inclusive.
4. 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.
5. 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.
6. Participant must be able and willing to comply with restrictions on prior and concomitant medication.
7. Negative for severe acute respiratory syndrome coronavirus-2 infection.
8. Non-smoker and not using any nicotine-containing products
9. Negative screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates, methadone, tricyclic antidepressants) and alcohol.
10. 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.
11. Adherence to effective contraception or are proven post-menopausal
12. 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
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known hypersensitivity to investigational medicinal product (IMP) ingredients or history of
a significant allergic reaction to IMP ingredients as determined by the Investigator
2. 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
3. History of or a current immunosuppressive condition (e.g. human immunodeficiency virus
[HIV] infection).
4. Having any illness, judged by the Investigator as clinically significant, in the 3 months prior to the first dose of study drug.
5. Current clinically significant infection or clinically significant infection within 6 months of
first dose of study drug
6. History of chronic or recurrent infectious disease within the last 2 years.
7. 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.
8. Pregnant or breast feeding participants.
9. 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,
10. 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)
11. Clinically significant abnormalities detected on 12-lead ECG
12. Clinically significant abnormalities detected on vital signs.
13. Significant blood loss (including blood donation [>500 mL]), or transfusion of any blood
product within 12 weeks prior to Screening.
14. Treatment with any drug known to have a potential for major organ toxicity in the last
3 months before the first dose of this study drug.
15. 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.
16. Vaccination with live virus, attenuated live virus, or any live viral components within the
6 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.
17. 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.
18. Active drug or alcohol abuse
19. Consumption of a large quantity of caffeinated coffee or tea (>6 cups per day) or equivalent.
20. 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.
21. 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.
22. Investigator or other study site staff who is directly involved in the conduct of the study and their relatives.
23. 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.
24. Previous participation in Part 1 or 2 of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be concealed to their allocation to the Fed or Fasted treatment groups and will be allocated via central randomisation to a treatment sequence.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Potential for bias will be reduced by central randomisation of participants to a treatment sequence.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis
Assessment of a food effect of a high-calorie, high-fat breakfast will be done by comparing data from the oral capsule/s in the fasted state with that obtained in the fed state.

For the comparisons, ln-transformed PK parameters (Cmax, C24, AUC0-24, t½) of SDC-1801 will be subjected to a mixed-effects model. Point estimates of ln-transformed data for treatment Y (fed state) versus ln-transformed SDC-1801 data for treatment X (fasted state) will be calculated as the geometric mean ratio, expressed as a percentage. Treatment X will be considered as the reference treatment for the comparison.

Food effect will be evaluated by review of the 90% confidence interval obtained from the comparison of treatment Y vs treatment X.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
4/06/2023
Actual
8/11/2023
Date of last participant enrolment
Anticipated
7/05/2024
Actual
22/11/2023
Date of last data collection
Anticipated
4/06/2024
Actual
9/12/2023
Sample size
Target
16
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 313551 0
Commercial sector/Industry
Name [1] 313551 0
Sareum Limited
Country [1] 313551 0
United Kingdom
Primary sponsor type
Commercial sector/Industry
Name
Pharmaceutical Solutions Australia Pty Ltd
Address
C/O - BDO
Level 11, 1 Margaret Street
Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 315330 0
Commercial sector/Industry
Name [1] 315330 0
Pampisford Pty Ltd
Address [1] 315330 0
Level 17, HWT Tower, 40 City Road, Southbank VIC 3006
Country [1] 315330 0
Australia
Other collaborator category [1] 282604 0
Commercial sector/Industry
Name [1] 282604 0
Pharmaceutical Solutions Australia Pty Ltd
Address [1] 282604 0
C/O - BDO
Level 11, 1 Margaret Street
Sydney NSW 2000
Country [1] 282604 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312733 0
Alfred Health Ethics Committee
Ethics committee address [1] 312733 0
55 Commercial Road
Melbourne, Vic 3004
Ethics committee country [1] 312733 0
Australia
Date submitted for ethics approval [1] 312733 0
29/03/2023
Approval date [1] 312733 0
04/05/2023
Ethics approval number [1] 312733 0

Summary
Brief 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.

In addition, the effect of food on SDC-1801 PK will be evaluated to characterise the PK of SDC-1801 in fasted and fed conditions and to guide the selection of a dosing regimen for use in further studies.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 125710 0
Dr Sam Francis
Address 125710 0
Nucleus Network
Level 5, Burnet Tower
89 Commercial Road
Melbourne, Victoria, 3004
Country 125710 0
Australia
Phone 125710 0
+61 466 604 801
Fax 125710 0
+61 3 9001 5810
Email 125710 0
s.francis@nucleusnetwork.com.au
Contact person for public queries
Name 125711 0
Dr Tim Mitchell
Address 125711 0
Sareum Ltd
2A Langford Arch
Cambridge CB22 3FX
United Kingdom
Country 125711 0
United Kingdom
Phone 125711 0
+44 1223 497703
Fax 125711 0
Email 125711 0
Tim.Mitchell@sareum.co.uk
Contact person for scientific queries
Name 125712 0
Dr John Reader
Address 125712 0
Sareum Ltd
2A Langford Arch
Cambridge CB22 3FX
United Kingdom
Country 125712 0
United Kingdom
Phone 125712 0
+441223497704
Fax 125712 0
Email 125712 0
jreader@sareum.co.uk

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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No documents have been uploaded by study researchers.

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