Safety, Pharmacodynamics, and Pharmacokinetics of Orally Administered BLD-2660 in Subjects With IPF

NCT04244825 | Withdrawn Phase 2 DMC

• 1 other identifier: B-2660-203
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Conditions

Idiopathic Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (4)

• Observed changes in ILK from baseline

  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.

  58 days

• Observed changes in spectrin from baseline

  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.

  58 days

• Observed changes in ezrin from baseline

  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.

  58 days

• Observed changes in S100A9 from baseline

  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.

  58 days

Secondary Outcomes (5)

• 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

• Maximum observed drug concentration (Cmax)

  58 days

• Time of the maximum drug concentration (Tmax)

  58 days

• Incidence of Treatment-Emergent Adverse Events as assessed by PI and SMC

  58 days

Study Arms (8)

Cohort 1a BLD-2660

EXPERIMENTAL

900 mg (6 x 150 mg capsules) BID

Drug: BLD-2660

Cohort 1b BLD-2660

EXPERIMENTAL

900 mg (6 x 150 mg capsules) BID (Optional)

Drug: BLD-2660

Cohort 2 BLD-2660

EXPERIMENTAL

600 mg (4 x 150 mg capsules) BID

Drug: BLD-2660

Cohort 3 BLD-2660

EXPERIMENTAL

300 mg (2 x 150 mg capsules) BID

Drug: BLD-2660

Cohort 1a Placebo

PLACEBO COMPARATOR

900 mg (6 x 150 mg capsules) BID

Drug: Control: Placebo

Cohort 1b Placebo

PLACEBO COMPARATOR

900 mg (6 x 150 mg capsules) BID (Optional)

Drug: Control: Placebo

Cohort 2 Placebo

PLACEBO COMPARATOR

600 mg (4 x 150 mg capsules) BID

Drug: Control: Placebo

Cohort 3 Placebo

PLACEBO COMPARATOR

300 mg (2 x 150 mg capsules) BID

Drug: Control: Placebo

Interventions

BLD-2660 DRUG

BLD-2660 - 150 mg capsules '00' size (PO) BID

Cohort 1a BLD-2660; Cohort 1b BLD-2660; Cohort 2 BLD-2660; Cohort 3 BLD-2660

Control: Placebo DRUG

Placebo - 150 mg capsules '00' size (PO) BID

Cohort 1a Placebo; Cohort 1b Placebo; Cohort 2 Placebo; Cohort 3 Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• All subjects (male or female) who are of childbearing potential must agree to use highly effective contraception during the study.
• Male subjects and female partners of male subjects must continue to use highly effective contraception for 90 days after the last dose of study drug (see Medicines and Healthcare products Regulatory Agency, 2019 for further guidance regarding highly effective contraception). Male subjects must agree not to donate sperm for 90 days after last dose of study drug.
• Female subjects and male partners of female subjects must continue to use highly effective contraception for 60 days after the last dose of study drug. Female subjects should not donate oocytes during this time.
• Female subjects of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day (-1). Women of childbearing potential (WOCBP) must agree to undergo pregnancy testing at regular intervals throughout the study.
• Female subjects not of childbearing potential as defined by being postmenopausal (with cessation of regular menstrual periods for at least 1 year), confirmed by follicle stimulating hormone (FSH) level, or be surgically sterile.
• Informed Consent

You may not qualify if:

• 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.
• Diagnostic Assessments
• Positivity for Human Immunodeficiency Virus (HIV) antibody (HIV-1 and/or HIV-2) and/or HIV-1 p24 antigen.
• Positivity for Hepatitis C virus antibody (HCV Ab or anti-HCV) and/or Hepatitis B surface antigen (HBsAg).
• Absolute neutrophil count \<1700/µL.
• Significant hypoxia, requiring \>2 L/min oxygen to maintain a resting oxygen saturation \>89%.
• Poor exercise tolerance.

Sponsors & Collaborators

• Blade Therapeutics: lead

Study Sites (1)

Blade Research Site

London, United Kingdom

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: January 3, 2020
• First Posted: January 28, 2020
• Study Start: December 15, 2019
• Primary Completion: September 14, 2020
• Study Completion: November 5, 2020
• Last Updated: March 4, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)