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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04244825
Recruitment Status : Not yet recruiting
First Posted : January 28, 2020
Last Update Posted : January 28, 2020
Sponsor:
Information provided by (Responsible Party):
Blade Therapeutics

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

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: BLD-2660 Drug: Control: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Cohort 1a BLD-2660
900 mg (6 x 150 mg capsules) BID
Drug: BLD-2660
BLD-2660 - 150 mg capsules '00' size (PO) BID

Experimental: Cohort 1b BLD-2660
900 mg (6 x 150 mg capsules) BID (Optional)
Drug: BLD-2660
BLD-2660 - 150 mg capsules '00' size (PO) BID

Experimental: Cohort 2 BLD-2660
600 mg (4 x 150 mg capsules) BID
Drug: BLD-2660
BLD-2660 - 150 mg capsules '00' size (PO) BID

Experimental: Cohort 3 BLD-2660
300 mg (2 x 150 mg capsules) BID
Drug: BLD-2660
BLD-2660 - 150 mg capsules '00' size (PO) BID

Placebo Comparator: Cohort 1a Placebo
900 mg (6 x 150 mg capsules) BID
Drug: Control: Placebo
Placebo - 150 mg capsules '00' size (PO) BID

Placebo Comparator: Cohort 1b Placebo
900 mg (6 x 150 mg capsules) BID (Optional)
Drug: Control: Placebo
Placebo - 150 mg capsules '00' size (PO) BID

Placebo Comparator: Cohort 2 Placebo
600 mg (4 x 150 mg capsules) BID
Drug: Control: Placebo
Placebo - 150 mg capsules '00' size (PO) BID

Placebo Comparator: Cohort 3 Placebo
300 mg (2 x 150 mg capsules) BID
Drug: Control: Placebo
Placebo - 150 mg capsules '00' size (PO) BID




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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 Outcome Measures :
  1. Area under the drug concentration-time curve from time zero to the last measurable concentration (AUC0-last) [ Time Frame: 58 days ]
    Measured by plasma concentration

  2. AUC from time 0 to infinity (AUC0-inf) [ Time Frame: 58 days ]
    Measured by plasma concentration

  3. Maximum observed drug concentration (Cmax) [ Time Frame: 58 days ]
    Measured by plasma concentration

  4. Time of the maximum drug concentration (Tmax) [ Time Frame: 58 days ]
    Measured by plasma concentration

  5. Incidence of Treatment-Emergent Adverse Events as assessed by PI and SMC [ Time Frame: 58 days ]
    AEs will be assessed by determining the incidence, severity, and dose relationship of adverse events.



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

  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.
  3. Forced vital capacity (FVC) >45% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) >30% predicted.
  4. Alanine aminotransferase (ALT) within normal limit (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 <0.35).
  7. 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.
  8. All subjects (male or female) who are of childbearing potential must agree to use highly effective contraception during the study.
  9. 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.
  10. 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.
  11. 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.
  12. 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

  13. 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.

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 <0.65).
  6. Other explanation for lung fibrosis, including but not limited to radiation, sarcoidosis, bronchiolitis obliterans organizing pneumonia, collagen vascular disease, hypersensitivity pneumonitis, etc.
  7. IPF exacerbation within last 60 days.
  8. 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

  9. Positivity for Human Immunodeficiency Virus (HIV) antibody (HIV-1 and/or HIV-2) and/or HIV-1 p24 antigen.
  10. Positivity for Hepatitis C virus antibody (HCV Ab or anti-HCV) and/or Hepatitis B surface antigen (HBsAg).
  11. Absolute neutrophil count <1700/µL.
  12. Significant hypoxia, requiring >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, investigational device, or approved therapy for investigational use within 30 days prior to the first study drug administration, or five half-lives, whichever is longer.

    Other Exclusions

  23. Blood donation or significant blood loss within 60 days prior to the first study drug administration.
  24. Plasma donation within 7 days prior to the first study drug administration.
  25. Female subjects who are pregnant or breastfeeding.
  26. History or presence of alcohol or drug abuse (including recreational marijuana use) within the 2 year prior to the first study drug administration, and unwillingness to be totally abstinent during the dosing period.
  27. Active smoker, smoking history or vaping within 4 weeks prior to the first dose of study drug. Subjects only using Nicotine replacement therapy (NRT) may be allowed per discretion of the Investigator.
  28. Subjects with an allergy to BLD-2660 or inactive components of BLD-2660.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04244825


Contacts
Layout table for location contacts
Contact: Maria Walters (650) 443-7366 mwalters@blademed.com
Contact: Joanne C Imperial, MD (650) 443-4316 jimperial@blademed.com

Sponsors and Collaborators
Blade Therapeutics

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Responsible Party: Blade Therapeutics
ClinicalTrials.gov Identifier: NCT04244825    
Other Study ID Numbers: B-2660-203
First Posted: January 28, 2020    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial