Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000011886
Ethics application status
Approved
Date submitted
26/11/2020
Date registered
11/01/2021
Date last updated
14/06/2022
Date data sharing statement initially provided
11/01/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A 2-part, randomised, double-blind, placebo-controlled study of the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of FTP 637 in healthy volunteers.
Scientific title
A 2-part, randomised, double-blind, placebo-controlled study of the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of FTP 637 in healthy volunteers.
Secondary ID [1] 302718 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Psoriasis 319635 0
Condition category
Condition code
Skin 317576 317576 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 319033 0
Treatment: Drugs
Comparator / control treatment
A solution containing, Citric Monohydrate, Sodium Citrate Dihydrate, Hypromellose, Betadex Sulfobutyl Ether Sodium, Deionized water, and a bittering agent, Denatonium Benzoate, will be used as the placebo. The required volume of this solution to match the volume of the corresponding FTP-637 dose will be dispensed for oral administration to participants.
Control group
Placebo

Outcomes
Primary outcome [1] 325669 0
Safety and tolerability of single and 7-day repeat oral doses of FTP-637 as assessed by Adverse Events (assessed accordingly to Common Terminology Criteria for Adverse Events), Physical Examination (change in examination findings), change in weight (digital scale), Vital signs (Blood pressure and heat rate measured using a digital BP monitor), ECG (12 and 5 lead), and Clinical Laboratory parameters (blood biochemistry, hematology and coagulation, and urinalysis).
Timepoint [1] 325669 0
Physical examinations:
Part A:
Full Physical Examinations will be performed at Screening and Day 7 (end of study).
Symptom Directed Physical Examinations will be performed at Day -1, Day 1 pre dose, Day 2, day 3 and Day 4 (cohort 4 only).
Part B:
Full Physical Examinations will be performed at Screening and Day 14 (end of study).
Symptom Directed Physical Examinations will be performed at Day -1, Day 1 pre dose, Day2, Day 3, Day 4, Day 5, Day 6 pre dose, Day 7 pre dose, Day 8 and day 9.

Body weight will be measured:
Part A: Screening, Day-1 and Day 7 (end of study)
Part B Screening, Day-1, Day 7 and day 14 (end of study)

Vital sign assessments will be performed:
Part A:
Screening, Day-1, Day 1 Pre dose, 30 mins post dose, 2hrs post dose, 6hrs post dose, 12hrs post dose, 24hrs post dose (Day 2), 48hrs post dose (Day 3), 72hrs post dose (Day 4 - cohort 4 only) and approximately 144 hrs post dose (Day 7).
Part B:
Screening, Day-1, Pre dose, 30 mins post dose and 6hrs post dose Day 1, Pre dose, 2hrs, 6hrs and 12hrs post dose on Day 7, and also once on Day 2, 3, 4, 5, 6, 8, 9 and 14 (end of study).

12 lead ECG assessments will be completed as follows:
Part A:
Screening, Day-1, Day 1 1 hr, 45 min and 30 min Pre dose, 30 mins , 1hr, 2hrs, 4 hrs, 6hrs, 8hrs, 12hrs post dose, 24hrs post dose (Day 2), 48hrs post dose (Day 3), 72hrs post dose (Day 4 - cohort 4 only) and approximately 144 hrs post dose (Day 7 end of study).
Part B:
Screening, Day-1, Day 1 1 hr, 45 min and 30 min Pre dose, and 4hrs post dose Day 1, Pre Dose and 4hrs post dose on Day 2, 3, 4, 5 and 6. Day 7 30 min pre dose, 1hr, 2hrs, 4 hrs, 6hrs, 8hrs, 12hrs post dose, 24hrs post dose (day 8), 48hrs post dose (Day 9) and Day 14 (end of study).

Safety Laboratory testing for Serum Chemistry, Haematology, Coagulation and urinalysis, will be completed at the following time points:
Part A: Screening, Day -1, Day 1 6hrs post dose, Day 2 and Day 7 (end of study)
Part B: Screening, Day -1, Day 1 6hrs post dose, Day 2, Day 4, Day 6 pre dose, Day 8 and Day 14 (end of study)

Adverse events will be recorded from the time that a subject signs consent until the final follow up visit. Site staff will question subjects on their health when conducting other assessments throughout the trial. Adverse events will be assessed by study investigators. Adverse events known to be associated with tyrosine kinase 2 inhibitors include nasopharyngitis, headache, diarrhea, upper respiratory tract infection, acne and nausea.
Secondary outcome [1] 388742 0
Pharmacokinetics (PK) of FTP-637 in plasma following administration of single and 7-day repeat oral doses in healthy adult volunteers.
Timepoint [1] 388742 0
PK sampling is to be completed as follows:
Part A:
Pre dose, and 5min, 10min, 15min, 30min, 45min, 1hr, 1.5hr, 2hr, 4hr, 6hr, 8hr, 12hr, 24hr and 48hrs post dose.

Part B:
Pre dose, and 5min, 10min, 15min, 30min, 45min, 1hr, 1.5hr, 2hr, 4hr, 6hr, 8hr, 12hr, 24hr post dose on Day 1 and 7; pre dose Day 3, 4, 5 and 6, and day 9.
Secondary outcome [2] 388743 0
Pharmacokinetics (PK) of FTP-637 as assessed by urine and faeces analysis after a single oral dose in healthy adult volunteers..
Timepoint [2] 388743 0
Urine and faecal sample analysis will occur in Part A Cohort 4 from check in (day -1) until check out from the clinical unit (Day 4)
Secondary outcome [3] 388744 0
Pharmacodynamics (PD) of biomarker changes relevant to the TYK2 pathway associated with
administration of FTP-637 in healthy adult volunteers (Part B only). Outcome measured by collection of blood samples.
Timepoint [3] 388744 0
PD Plasma sampling to collected in Part B at the following timepoints:
Day1 pre dose; Day 6 pre dose, 2 hrs post dose (Pre Roferon-A dose), 4hrs post dose, 6hrs post dose, 10hrs post dose, 24hrs post dose and 48hrs post dose.
Secondary outcome [4] 388745 0
Exploratory:
Effect of FTP-637 on QT interval corrected using the Fridericia method (QTcF) and other ECG parameters, including exposure-related changes in QTcF
Timepoint [4] 388745 0
12 lead ECG assessments will be completed as follows:
Part A:
Screening, Day-1, Day 1 1 hr, 45 min and 30 min Pre dose, 30 mins , 1hr, 2hrs, 4 hrs, 6hrs, 8hrs, 12hrs post dose, 24hrs post dose (Day 2), 48hrs post dose (Day 3), 72hrs post dose (Day 4 - cohort 4 only) and approximately 144 hrs post dose (Day 7 end of study).
Part B:
Screening, Day-1, Day 1 1 hr, 45 min and 30 min Pre dose, , 30 mins post dose and 4hrs post dose Day 1, Pre Dose and 4hrs post dose on Day 2, 3, 4, 5 and 6. Day 7 30 min pre dose, 1hr, 2hrs, 4 hrs, 6hrs, 8hrs, 12hrs post dose, 24hrs post dose (day 8), 48hrs post dose (Day 9) and Day 14 (end of study).
Secondary outcome [5] 390048 0
Exploratory:
Pharmacodynamics (PD) of biomarker changes in Lymphocyte count in plasma, associated with administration of FTP-637 in healthy adult volunteers (Part B only).
Timepoint [5] 390048 0
PD plasma sampling to collected in Part B at the following timepoints:
Day1 pre dose; Day 6 pre dose, 2 hrs post dose (Pre Roferon-A dose), 4hrs post dose, 6hrs post dose, 10hrs post dose, 24hrs post dose and 48hrs post dose.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
29/01/2021
Actual
17/02/2021
Date of last participant enrolment
Anticipated
17/11/2021
Actual
19/01/2022
Date of last data collection
Anticipated
30/11/2021
Actual
4/02/2022
Sample size
Target
96
Accrual to date
Final
87
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 307146 0
Commercial sector/Industry
Name [1] 307146 0
Alumis Inc (formerly Esker Therapeutics, Inc)
Country [1] 307146 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Alumis Inc (formerly Esker Therapeutics, Inc)
Address
611 Gateway Blvd, Suite 820, South San Francisco, CA 94080 USA
Country
United States of America
Secondary sponsor category [1] 307731 0
Commercial sector/Industry
Name [1] 307731 0
Avance Clinical Pty Ltd
Address [1] 307731 0
Level 1, 2 Ann Nelson Drive,
Thebarton
SA, 5031
Australia
Country [1] 307731 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307259 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 307259 0
Ethics committee country [1] 307259 0
Australia
Date submitted for ethics approval [1] 307259 0
11/11/2020
Approval date [1] 307259 0
10/12/2020
Ethics approval number [1] 307259 0
2020-11-1116

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106598 0
Prof Sepehr Shakib
Address 106598 0
CMAX Clinical Research Pty Ltd
Level 5, 18 a North Terrace
Adelaide, SA, 5000
Australia
Country 106598 0
Australia
Phone 106598 0
+61 411 100 278
Fax 106598 0
Email 106598 0
[email protected]
Contact person for public queries
Name 106599 0
Sepehr Shakib
Address 106599 0
CMAX Clinical Research Pty Ltd
Level 5, 18 a North Terrace
Adelaide, SA, 5000
Australia
Country 106599 0
Australia
Phone 106599 0
+61 411 100 278
Fax 106599 0
Email 106599 0
[email protected]
Contact person for scientific queries
Name 106600 0
Sepehr Shakib
Address 106600 0
CMAX Clinical Research Pty Ltd
Level 5, 18 a North Terrace
Adelaide, SA, 5000
Australia
Country 106600 0
Australia
Phone 106600 0
+61 411 100 278
Fax 106600 0
Email 106600 0
[email protected]

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

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.