A Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate Pharmacodynamics, Pharmacokinetics, and Safety of BLD-2660 Administered Orally in Subjects With Idiopathic Pulmonary Fibrosis
Overview
- Phase
- Phase 2
- Intervention
- BLD-2660
- Conditions
- Idiopathic Pulmonary Fibrosis
- Sponsor
- Blade Therapeutics
- Locations
- 1
- Primary Endpoint
- Observed changes in spectrin from baseline
- Status
- Withdrawn
- Last Updated
- 5 years ago
Overview
Brief Summary
A Phase 2a, Double-Blind, Placebo-Controlled Study to Evaluate Pharmacodynamics, Pharmacokinetics, and Safety of BLD-2660 Administered Orally in Subjects with Idiopathic Pulmonary Fibrosis
Detailed Description
This is a Phase 2a, double-blind, placebo-controlled, multicentre, adaptive design study of BLD-2660 in subjects with IPF. The study will include a Screening period, a Treatment period, and a Follow-up period. Data on PK, PD, and biomarker activity will be observed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be eligible for inclusion into this study, each subject must fulfill the following inclusion criteria within 20 days prior to Randomization on Day 1:
- •Age and Gender
- •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
- •Subjects with diagnosis of IPF as defined by the American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of Idiopathic Interstitial Pneumonia.
- •Forced vital capacity (FVC) \>45% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) \>30% predicted.
- •Alanine aminotransferase (ALT) within normal limit (WNL).
- •Aspartate aminotransferase (AST) and alkaline phosphatase (ALP) ≤1.2× upper limit of normal (ULN).
- •Total bilirubin ≤ULN (isolated bilirubinemia ≤2× ULN is acceptable if direct bilirubin to total bilirubin ratio \<0.35).
- •Body mass index (BMI) up to 35 kg/m2 inclusive. 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.
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
- •Medical Conditions
- •Recent (less than 6 weeks) significant wound (in the opinion of the Investigator), or presence of an ongoing non-healing skin wound or ulcer.
- •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 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.
- •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.
- •Extensive chronic obstructive pulmonary disease (where extent of emphysema \>extent of fibrosis on computerised tomography (CT) scan or FEV1: FVC ratio \<0.65).
- •Other explanation for lung fibrosis, including but not limited to radiation, sarcoidosis, bronchiolitis obliterans organizing pneumonia, collagen vascular disease, hypersensitivity pneumonitis, etc.
- •IPF exacerbation within last 60 days.
- •A history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subjects' participation for the full duration of the study, or is not in the best interest of the subjects to participate, in the opinion of the Investigator.
Arms & Interventions
Cohort 1b BLD-2660
900 mg (6 x 150 mg capsules) BID (Optional)
Intervention: BLD-2660
Cohort 1a BLD-2660
900 mg (6 x 150 mg capsules) BID
Intervention: BLD-2660
Cohort 2 BLD-2660
600 mg (4 x 150 mg capsules) BID
Intervention: BLD-2660
Cohort 3 BLD-2660
300 mg (2 x 150 mg capsules) BID
Intervention: BLD-2660
Outcomes
Primary Outcomes
Observed changes in spectrin from baseline
Time Frame: 58 days
Change in RLU of BAL fluid analyzed by spectrin-targeting ELISA assay. Analysis of difference in RLU correlates to change in cellular spectrin from baseline.
Observed changes in ILK from baseline
Time Frame: 58 days
Change in RLU of BAL fluid analyzed by ILK-targeting ELISA assay. Analysis of difference in RLU correlates to change in cellular ILK from baseline.
Observed changes in ezrin from baseline
Time Frame: 58 days
Change in RLU of BAL fluid analyzed by ezrin-targeting ELISA assay. Analysis of difference in RLU correlates to change in cellular ezrin from baseline.
Observed changes in S100A9 from baseline
Time Frame: 58 days
Change in RLU of BAL fluid analyzed by S100A9-targeting ELISA assay. Analysis of difference in RLU correlates to change in cellular S100A9 from baseline.
Secondary Outcomes
- Maximum observed drug concentration (Cmax)(58 days)
- Incidence of Treatment-Emergent Adverse Events as assessed by PI and SMC(58 days)
- Area under the drug concentration-time curve from time zero to the last measurable concentration (AUC0-last)(58 days)
- AUC from time 0 to infinity (AUC0-inf)(58 days)
- Time of the maximum drug concentration (Tmax)(58 days)