Idiopathic Pulmonary Fibrosis MedDRA version: 21.1 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: BLD-2660
Product Code: BLD-2660
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: None
Current Sponsor code: BLD-2660
Other descriptive name: BLD-2660
Concentration unit: mg millig
Sponsors
Blade Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for inclusion into this study, each subject must fulfil the following inclusion criteria within 20 days prior to Randomisation on Day 1. Age and Gender 1. Male subjects 45 years of age and over, or female subjects 50 years of age and over, at the time of signing the informed consent. Diagnosis and disease characteristics 2. Subjects with diagnosis of IPF as defined by the American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of Idiopathic Interstitial Pneumonia (Raghu, 2018). 3. FVC >45% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) >30% predicted. 4. Alanine aminotransferase (ALT) within normal limits (WNL). 5. Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) =1.2 × upper limit of normal (ULN). 6. Total bilirubin =ULN (isolated bilirubinemia =2× ULN is acceptable if direct bilirubin to total bilirubin ratio =65 years) yes F.1.3.1 Number of sub
Exclusion criteria
Exclusion criteria: To be eligible for inclusion into this study, each subject must violate none of the following exclusion criteria within 20 days prior to Randomisation on Day 1: Medical Conditions 1. Recent (less than 6 weeks) significant wound (in the opinion of the Investigator), or presence of an ongoing non-healing skin wound or ulcer. 2. 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. 3. Active infection (diagnosed or suspected) or history of recurrent infections, including but is not limited to, bronchitis, pneumonia, sinusitis, urinary tract infection, cellulitis or chronic ongoing infectious disease within 4 weeks prior to first dose of study drug. Note: Rescreening will be permitted after 28 days if an infection leads to screening failure. 4. Active malignancy and/or history of malignancy in the past 5 years, except for non-melanoma skin cancer, carcinoma in situ of the breast that has been successfully treated, carcinoma in situ of the cervix that has been successfully treated, early stage, untreated prostate cancer, or prostate cancer with completion of treatment >2 years prior to Screening. 5. Extensive chronic obstructive pulmonary disease (where extent of emphysema >extent of fibrosis on computerised tomography (CT) scan or FEV1: FVC ratio 2 L/min oxygen to maintain a resting oxygen saturation >89%. 13. Poor exercise tolerance. 14. Serum troponin I level >ULN. Prior/Concomitant Therapy 15. Use of anticoagulants that prolong Prothrombin time (PT)/ International normalised ratio (INR). 16. Use of anticoagulants within 2 days of Day (-1) (bronchoscopy) Note: The subjects who cannot discontinue the anticoagulants within 2 days of Day (-1) bronchoscopy will be excluded. 17. Treatment with any anti-fibrotic therapy (pirfenidone or nintedanib) within 30 days of Screening. 18. Immunosuppressive therapy within 3 months prior to first dose of study drug unless for non-IPF indication). 19. Use of oral steroids >10 mg/day (or prednisolone equivalent). Note: If the subject is on steroid dose equivalent to 10 mg/day prednisone or more, the Investigator may decide if the tapering down to the dose of 10 mg/day prednisone is possible and safe. 20. Start of new biologic or change in biologic dose within 24 weeks prior to Day 1. 21. Cyclophosphamide within 6 months prior to the first dose of study drug (unless for other indication). Prior/Concurrent Clinical Study Experience 22. Administration of another investigational product, investigation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PRIMARY OBJECTIVE • To establish the study drug interaction with its intended target in cells isolated from Bronchoalveolar lavage • To evaluate biochemical and physiologic effects of the study drug (Pharmacodynamics) and to evaluate the indicators or markers in the blood (Biomarkers) and Bronchoalveolar lavage fluid. ;Secondary Objective: • To study how the BLD-2660 enters, moves through and exits the body (Pharmacokinetics) in IPF subjects. • To establish safety and tolerability of BLD-2660 in subjects with IPF.;Primary end point(s): The primary endpoints of the study are: • Change from baseline in calpain substrates, (i.e., ILK, spectrin, ezrin and/or S100A9) in BAL cells; • Change from baseline in downstream PD biomarkers (e.g. PAI-1, IL-6, and/or CCL18) in BAL fluid; • Change from baseline in blood biomarkers that correlate with collagen formation and degradation including Pro-C3, C1M and C3M.;Timepoint(s) of evaluation of this end point: • Change from baseline in calpain substrates, (i.e., ILK, spectrin, ezrin and/or S100A9) in BAL cells - Evaluated on Day (-1) and Day 27 • Change from baseline in downstream PD biomarkers (e.g. PAI-1, IL-6, and/or CCL18) in BAL fluid - Evaluated on Day (-1) and Day 27 • Change from baseline in blood biomarkers that correlate with collagen formation and degradation including Pro-C3, C1M and C3M - Evaluated on Day (-1), 27 and 42 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic Endpoints: • PK parameters to be estimated on Days 1 and 28 by noncompartmental analysis (NCA) are: maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the curve to the final concentration = Lower Limit of Quantification [LLOQ] (AUC0-t) or to the end of the 12-hour dosing interval (AUC0-12). Additional analyses may be performed as deemed necessary upon review of the data; Safety Endpoints: • Incidence, nature, and severity of adverse events (AEs) and serious adverse events (SAEs); • Changes from baseline in electrocardiogram (ECG), vital signs, physical examinations and the following clinical laboratory values: haematology, clinical chemistry, coagulation and urinalysis; • Proportion of subjects with troponin elevations leading to discontinuation of study drug; • Proportion of subjects with troponin elevations that persist on retesting as >first elevated troponin value while still on study drug.;Timepoint(s) of evaluation of this end point: Pharmacokinetic Endpoints evaluated on Days 1 and 28 Safety Endpoints evaluated during each study visit | — |
Countries
United Kingdom
Contacts
Public ContactDaven Mody
Blade Therapeutics, Inc.
Outcome results
None listed