A Phase 1, Evaluate the Safety, Tolerability, and Pharmacokinetics of INS018_055 in Healthy Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 10 July 2023
• Main ID: NCT05154240
• Date of registration: 17/11/2021
• Prospective Registration: Yes
• Primary sponsor: InSilico Medicine Hong Kong Limited
• Public title: A Phase 1, Evaluate the Safety, Tolerability, and Pharmacokinetics of INS018_055 in Healthy Subjects
• Scientific title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Oral Single and Multiple Ascending Doses, Parallel Group Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of INS018_055 in Healthy Subjects
• Date of first enrolment: February 21, 2022
• Target sample size: 78
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT05154240
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

New Zealand

Contacts

• Name: Christopher J Wynne, MBChB
• Affiliation: New Zealand Clinical Research

Key inclusion & exclusion criteria

Inclusion Criteria:

1. The subject is a male or female 18 to 55 years of age, inclusive.

2. The subject has a body mass index 18 to 32 kg/m2, inclusive, and a total body weight
=50 kg, inclusive, at screening.

3. The subject is considered by the investigator to be in good general health as
determined by medical history, clinical laboratory test results, vital sign
measurements, 12-lead ECG results, and physical examination findings at screening.

4. Female subjects of childbearing potential must be non-pregnant and non-lactating and
must use one of the methods of contraception listed below for the duration of the
treatment until at least 28 days after the last dose of the study drug, or be
surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral
oophorectomy), or postmenopausal (defined as amenorrhea 12 consecutive months and
documented plasma follicle stimulating hormone level >40 IU/mL). Female subjects must
have a negative pregnancy test at screening and before the first dose of study drug.

Highly effective methods of contraception are those that result in a failure rate of
less than 1% per year when used consistently. Examples are provided below:

1. Implant contraceptive (eg, Jadelle®)

2. Intrauterine device containing either copper or levonorgestrel (eg, Mirena®)

3. Male sterilization with absence of sperm in the post-vasectomy ejaculate

OR an effective method that result in a failure rate of less than 5% to 10% per
year. Examples are provided below:

4. Injectable contraceptive (eg, Depo Provera)

5. Oral contraceptive pill (combined hormonal contraceptive pill or progestogen-only
'mini-pill')

6. Vaginal contraceptive ring (eg, NuvaRing®)

Female subjects must also agree not to donate eggs, from dosing until at least 28 days
after the last dose of study drug.

A male subject and his female partner who is of childbearing potential must agree to
use one of the methods of contraception listed above for the duration of the treatment
until at least 28 days after the last dose of the study drug. A male subject must also
agree not to donate sperm, for the duration of the treatment until at least 28 days
after the last dose of the study drug.

5. The subject agrees to comply with all protocol requirements.

6. The subject is able to provide written informed consent.

Exclusion Criteria:

1. The subject has current evidence or history of clinically significant hematological,
renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric,
neurologic, or allergic disease (including drug allergies, but excluding untreated,
asymptomatic, seasonal allergies at time of dosing).

2. The subject has any condition possibly affecting drug absorption (eg, gastrectomy).

3. The subject has a history of cancer with the exception of adequately treated basal
cell or squamous cell carcinoma of the skin.

4. The subject has supine blood pressure (BP) >140 mm Hg (systolic) or >90 mm Hg
(diastolic), following at least 5 minutes of supine rest. If BP is >140 mm Hg
(systolic) or >90 mm Hg (diastolic), the BP should be repeated 2 more times and the
average of the 3 BP values should be used to determine the subject's eligibility at
screening.

5. The subject has 12-lead ECG demonstrating corrected QT interval by Fridericia (QTcF)
>450 msec, or a QRS interval >120 msec at screening. If QTcF exceeds 450 msec, or QRS
interval exceeds 120 msec, the ECG should be repeated 2 more times and the average of
the 3 QTcF (or QRS interval) values should be used to determine the subject's
eligibility.

6. The subject has ANY of the following abnormalities in clinical laboratory tests at
screening, as assessed by the study-specific laboratory and confirmed by a single
repeat, if deemed necessary:

1. Serum creatinine level above the upper limit of normal (ULN) or an estimated
glomerular filtration rate value <80 mL/min/1.73 m2 calculated with the Chronic
Kidney Disease Epidemiology Collaboration formula and the absence of protein in
urine, at screening.

2. Aspartate aminotransferase or alanine aminotransferase values more than >1.5 ×
ULN.

3. Fasting glucose >110 mg/dL (6.1 mmol/L).

4. Total bilirubin >1.5 × ULN.

5. Hematological values outside the normal reference range for local laboratory
results.

6. Positive fecal occult blood test at screening or at check-in (Day -1).

7. The subject has any medical history of disease that has the potential to cause a rise
in total bilirubin over the ULN. Subjects with borderline clinical laboratory values
outside the reference range may be included in the study if the investigator deems
that the values are not clinically significant.

Note: Subjects 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
8. The subject has a history of any lymphoproliferative disorder (such as Epstein Barr
Virus related lymphoproliferative disorder, as reported in some subjects on
immunosuppressive drugs), history of lymphoma, leukemia, myeloproliferative disorders,
multiple myeloma, or signs and symptoms suggestive of current lymphatic disease.

9. The subject has a history of relevant drug and/or food allergies (ie, allergy to any
study drug or excipients, or any significant food allergy that could preclude a
standard diet in the clinical unit).

10. The subject has a clinically significant infection currently or within 6 months of
first dose of study drug (eg, those requiring hospitalization or parenteral
antimicrobial therapy or opportunistic infections within the last 6 months), or a
history of chronic or recurrent infectious disease.

11. The subject has other severe acute or chronic medical or psychiatric condition
including recent (within the past year) or active suicidal ideation or behavior or
laboratory abnormality that may increase the risk associated with study participation
or investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the investigator, would make the subject
inappropriate for entry into this study.

12. The subject has or has had symptomatic herpes zoster or herpes simplex within 12
weeks, more than one episode of local herpes zoster, or a history (single episode) of



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: Placebo

Drug: INS018_055

Primary Outcome(s)

Number of participants with treatment-related adverse events based on subjective and objective examination [Time Frame: 12 months]

Secondary Outcome(s)

Maximum Plasma Concentration [Cmax] [Time Frame: 12 months]

Accumulation ratio (AR), calculated as AUC0-To (Day 10)/AUC0-To (Day 1) [Time Frame: 12 months]

Apparent total body clearance (CL/F) [Time Frame: 12 months]

Apparent volume of distribution (Vd/F) [Time Frame: 12 months]

Time to reach Cmax (Tmax) [Time Frame: 12 months]

AUC from time 0 extrapolated to infinity (AUC0-inf) [Time Frame: 12 months]

Total amount of drug excreted unchanged in urine from 0 to 24 hours after dosing (XU0-24) [Time Frame: 12 months]

Area under the plasma concentration versus time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-t) [Time Frame: 12 months]

Average concentration on Day 1 and Day 10 (Cav) [Time Frame: 12 months]

Peak to trough ratio calculated as Cmax/Ctrough [Time Frame: 12 months]

AR calculated as Cmax (Day 10)/Cmax (Day 1) [Time Frame: 12 months]

Terminal elimination rate constant (Kel) [Time Frame: 12 months]

Metabolite-to parent ratio based on Cmax calculated as Cmax, metabolite/Cmax, parent [Time Frame: 12 months]

Pre-dose concentrations on Days 1 through 10 (C trough) [Time Frame: 12 months]

Renal clearance (CLr) [Time Frame: 12 months]

Terminal elimination half-life (t1/2) [Time Frame: 12 months]

AUC from time 0 to the time of the dosing interval (To; AUC0-To) [Time Frame: 12 months]

Metabolite-to parent ratio based on AUC calculated as AUCmetabolite/AUCparent [Time Frame: 12 months]

Secondary ID(s)

INS018-055-001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors