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

NCT05154240 | Completed Phase 1 DMC

• 1 other identifier: INS018-055-001
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The sponsor is planning to conduct a Phase 1, randomized, double-blind, placebo-controlled, oral single and multiple ascending-doses, parallel group study to evaluate the safety, tolerability and PK of INS018\_055 in healthy subjects. The study will be conducted in 1 clinical site in the New Zealand, consisting of 2 parts: Part A (single ascending dose \[SAD\]) and Part B (multiple ascending dose \[MAD\]).

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

IPF

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events based on subjective and objective examination

  Subjective examination refers to the participant response to standard question to elicit any medically related changes in their well-being. Descriptive examination refers to laboratory values as reviewed by the investigator, physical examination findings and ECG Changes, or other documents that are relevant to participant safety. AEs will be classified as: Mild: These events require minimal or no treatment and do not interfere with the subject's daily activities. Moderate: These events result in a low level of inconvenience or require minor therapeutic measures. Moderate events may cause some interference with normal functioning. Severe: These events interrupt a subject's usual daily activity and may require systemic drug therapy or other treatment. Severe events are usually incapacitating.

  12 months

Secondary Outcomes (18)

• Maximum Plasma Concentration [Cmax]

  12 months

• Area under the plasma concentration versus time curve (AUC) from time 0 to the last quantifiable concentration (AUC0-t)

  12 months

• AUC from time 0 extrapolated to infinity (AUC0-inf)

  12 months

• AUC from time 0 to the time of the dosing interval (To; AUC0-To)

  12 months

• Accumulation ratio (AR), calculated as AUC0-To (Day 10)/AUC0-To (Day 1)

  12 months

Other Outcomes (1)

• Characterisation of CD4+ and CD8+ subpopulation of T cells after single dose and of the same after multiple oral escalating doses of INS018_055

  12 months

Study Arms (2)

INS018_055

ACTIVE COMPARATOR

oral doses of INS018\_055\_single dose; oral doses of INS018\_055\_multiple ascending dose over 10days.

Drug: INS018_055

Placebo

PLACEBO COMPARATOR

No active ingredient. Frequency similar to the 2 arms above.

Drug: Placebo

Interventions

INS018_055 DRUG

INS018\_055 is a small molecule compound. INS018\_055 has good solubility in water and was chemically and physically stable at different temperatures.

INS018_055

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject is a male or female 18 to 55 years of age, inclusive.
• The subject has a body mass index 18 to 32 kg/m2, inclusive, and a total body weight ≥50 kg, inclusive, at screening.
• 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.
• 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:
• Implant contraceptive (eg, Jadelle®)
• Intrauterine device containing either copper or levonorgestrel (eg, Mirena®)
• 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:
• Injectable contraceptive (eg, Depo Provera)
• Oral contraceptive pill (combined hormonal contraceptive pill or progestogen-only 'mini-pill')
• 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.
• The subject agrees to comply with all protocol requirements.

You may not qualify if:

• 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).
• The subject has any condition possibly affecting drug absorption (eg, gastrectomy).
• The subject has a history of cancer with the exception of adequately treated basal cell or squamous cell carcinoma of the skin.
• 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.
• 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.
• 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:
• 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.
• Aspartate aminotransferase or alanine aminotransferase values more than \>1.5 × ULN.
• Fasting glucose \>110 mg/dL (6.1 mmol/L).
• Total bilirubin \>1.5 × ULN.
• Hematological values outside the normal reference range for local laboratory results.
• Positive fecal occult blood test at screening or at check-in (Day -1).
• 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 \<ULN.
• 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.

Sponsors & Collaborators

• InSilico Medicine Hong Kong Limited: lead

Study Sites (1)

NZCR Ltd

Christchurch, 8011, New Zealand

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Christopher J Wynne, MBChB

  New Zealand Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 1, randomized, 2-part (Part A and B), first-in-human, double-blind, placebo controlled single and multiple ascending dose study designed to assess the safety, tolerability, and PK of INS018\_055 when administered as oral doses to healthy subjects. Additionally, this study will investigate the impact of food on the PK of INS018\_055. Part A (Single Ascending Dose \[SAD\]): Food Effect Assessment (Cohort 4 in Part A only): Part B (Multiple Ascending Dose \[MAD\]):

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 13, 2021
• Study Start: February 21, 2022
• Primary Completion: December 2, 2022
• Study Completion: December 2, 2022
• Last Updated: June 29, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)