Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BLD-0409 in Healthy Subjects

NCT04146805 | Completed Phase 1 DMC

• 1 other identifier: B-0409-101
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1a, Double Blind, Placebo-Controlled, Single-Center, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability Pharmacokinetics, and Pharmacodynamics of BLD-0409 in Healthy Volunteers

Conditions

Chronic Liver Disease; NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (11)

• Incidence of Adverse Events (AEs)

  AEs will be assessed by determining the incidence, severity, and dose relationship of adverse events

  up to 56 days

• Number of subjects with treatment-related subjects changes in physical examinations

  Assessed by performing physical examinations include general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes, from baseline by dose, through out the study. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

  up to 56 days

• Number of treatment subjects with treatment-related changes in heart rate

  Assessed by collecting and evaluating any observed changes in heart rate. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

  up to 56 days

• Number of treatment subjects with treatment-related changes in systolic & diastolic blood pressure

  Assessed by collecting and evaluating any observed changes in systolic \& diastolic blod pressure. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

  up to 56 days

• Number of treatment subjects with treatment-related changes in body temperature

  Assessed by collecting body temperature using a thermometer. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

  up to 56 days

• Number of subjects with treatment-related changes in ECG tracings

  Assessed by performing 12-lead ECGs, and evaluating ECG tracings from baseline, by dose. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

  up to 56 days

• Number of subjects with treatment-related changes in QTc intervals

  Assessed by performing 12-lead ECGs, and evaluating QTc intervals from baseline, by dose. Results in subjects dosed with BLD-0409 will be compared to those dosed with placebo.

  up to 56 days

• Number of subjects with treatment-related changes in hematology clinical laboratory test results.

  Assessed by collecting and analyzing subjects' blood from baseline by dose. Results in subjects dosed with BLD-0409 treatment will be compared to those dosed with placebo.

  up to 56 days

• Number of subjects with treatment-related changes in chemistry clinical laboratory test results.

  Assessed by collecting and analyzing subjects' blood from baseline by dose. Results in subjects dosed with BLD-0409 treatment will be compared to those dosed with placebo.

  up to 56 days

• Number of subjects with treatment-related changes in urinalysis clinical laboratory test results.

  Assessed by collecting and analyzing subjects' urine from baseline by dose. Results in subjects dosed with BLD-0409 treatment will be compared to those dosed with placebo.

  up to 56 days

• Number of subjects with treatment-related changes in serology clinical laboratory test results.

  Assessed by collecting and analyzing subjects' blood from baseline by dose. Results in subjects dosed with BLD-0409 treatment will be compared to those dosed with placebo.

  up to 56 days

Secondary Outcomes (13)

• Area under the drug concentration-time curve from time zero to the last measurable concentration (AUClast)

  up to 56 days

• Area under the drug concentration time curve from time 0 to infinity (AUC0-inf)

  up to 56 days

• Maximum observed drug concentration (Cmax)

  up to 56 days

• Time of the maximum drug concentration (tmax)

  up to 56 days

• Apparent terminal elimination rate constant (kel)

  up to 56 days

Study Arms (2)

Part 1SAD/Part 2 MAD:Active Treatment(BLD-0409)

EXPERIMENTAL

For each cohort in both study parts, 6 subjects will be randomized to active (BLD-0409). Study drug will be administered orally once a day, with an option to evaluate twice daily dosing (BID) in Part 2 MAD cohort(s)

Drug: BLD-0409

Part 1SAD/Part 2 MAD:Control(Matched Placebo)

PLACEBO COMPARATOR

For each cohort in both study parts, 2 subjects will be randomized to control (matched placebo). Study drug will be administered orally once a day, with an option to evaluate twice daily dosing (BID) in Part 2 MAD cohort(s).

Drug: Control: Placebo

Interventions

BLD-0409 DRUG

For each cohort in both study parts, 8 subjects will be randomized in a 6:2 ratio to active (BLD-0409) : control (matched placebo). Study drug will be administered orally once a day, with an option to evaluate twice daily dosing (BID) in Part 2 MAD cohort(s).

Part 1SAD/Part 2 MAD:Active Treatment(BLD-0409)

Control: Placebo DRUG

Subjects will be randomized in a 6:2 ratio to control (matched placebo). Study drug will be administered orally once a with an option to evaluate twice daily dosing (BID) in Part 2 MAD cohort(s).

Part 1SAD/Part 2 MAD:Control(Matched Placebo)

Eligibility Criteria

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

You may qualify if:

• Subjects are eligible to be included in the study only if all the following criteria apply:
• Age and Gender
• Male and female subjects 18-55 years of age (inclusive) at the time of signing the PICF.
• Diagnosis and disease characteristics
• Subjects must be in good general health, in the opinion of the Investigator, with no significant medical history, have no clinically significant abnormalities on physical examination at Screening, and/or before administration of the initial dose of study drug.
• Subjects must have clinical laboratory values within normal ranges or \< 1.2 times upper limit of normal (ULN) as specified by the testing laboratory, unless deemed not clinically significant (NCS) by the Investigator, with exception of liver function tests which cannot be above the ULN.
• Body mass index (BMI) 18 to ≤ 32 kg/m2. Reproductive Considerations Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For details refer to Appendix 4.
• Female subjects and female partners of male subjects must use double barrier contraception and refrain from oocyte donation from first dose of study drug and for 60 days after last dose of study drug. Estrogen-containing products are not allowed.
• Male subjects must agree to use highly effective, double barrier contraception and refrain from sperm donation from first dose of study drug and for 90 days after last dose of study drug.
• Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -1. Females not of childbearing potential must be surgically infertile or post-menopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle-stimulating hormone (FSH) level \> 40 mIU/mL at Screening.
• Informed Consent
• Subjects must provide signed informed consent prior to study entry and have the ability and willingness to attend and comply with the necessary visits at the study site.

You may not qualify if:

• Medical Conditions
• Recent (less than 6 weeks) wound, or presence of an ongoing non-healing skin wound.
• Presence of any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the subject will complete the study per protocol.
• Active malignancy and/or history of malignancy in the past 5 years, with the exception of completely excised non-melanoma skin cancer or low grade cervical intraepithelial neoplasia.
• Serious local or systemic infection within 1 month of Screening requiring antibiotic treatment or history of recurrent infections.
• Surgery within the past 3 months prior to the first study drug administration determined by the Investigator to be clinically relevant.
• Diagnostic Assessments
• Positive for human immunodeficiency virus (HIV) antibody or antigen.
• Positive hepatitis C virus (HCV) antibody or positive hepatitis B surface antigen (HBsAg).
• Systolic blood pressure (BP) \> 150 mmHg or \< 90 mmHg or diastolic BP \> 90 mmHg or \< 50 mmHg at Screening with one repeat allowed per the Investigator's discretion at Screening and Day -1.
• Heart rate \< 40 beats per minute (bpm) or \> 100 bpm at Screening.
• Prolonged QTcF (\>450 ms for males and \>470 ms for females), cardiac arrhythmia, or any clinically significant abnormality in the resting ECG, as judged by the Investigator.
• Females with heavy menstruating cycles and borderline-low iron studies. Prior Therapy
• All prescription and over the counter medications (including herbal medications), except for non-estrogen contraceptives, are prohibited within 7 days prior to the first study drug administration and throughout the entire duration of the study.
• Any estrogen-containing products, e.g., contraceptives, patch, cream, implants within 14 days prior to the first study drug administration.

Sponsors & Collaborators

• Blade Therapeutics: lead

Study Sites (1)

Scientia Clinical Research

Randwick, New South Wales, 2031, Australia

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: October 31, 2019
• Study Start: January 10, 2020
• Primary Completion: December 3, 2020
• Study Completion: April 12, 2021
• Last Updated: June 4, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)