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Saracatinib in the Treatment of Idiopathic Pulmonary Fibrosis (STOP-IPF)

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ClinicalTrials.gov Identifier: NCT04598919
Recruitment Status : Recruiting
First Posted : October 22, 2020
Last Update Posted : February 9, 2021
Sponsor:
Collaborators:
Yale University
Icahn School of Medicine at Mount Sinai
AstraZeneca
National Center for Advancing Translational Science (NCATS)
Information provided by (Responsible Party):
National Jewish Health

Brief Summary:

Scarring of the lung, termed pulmonary fibrosis (PF), is a chronic, progressive, and usually fatal disorder. While two anti-fibrotic drugs have recently been approved for treating PF of unknown cause (idiopathic pulmonary fibrosis or IPF), neither drug is curative, and nearly 40% of patients stop taking the prescribed drug within a year because of side effects. The study includes the use of saracatinib, an investigational drug originally developed to treat certain types of cancers, in the treatment of IPF in a Phase 1b/2a clinical trial.

The objectives of this study are to: i) evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics, and to explore the efficacy of saracatinib in IPF; ii) identify biomarkers of Src kinase activity and fibrogenesis linked to pulmonary fibrosis; and iii) explore the application of these biomarkers to assess the anti-fibrotic effect of saracatinib in IPF patients


Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis (IPF) Drug: Saracatinab Drug: Placebo Phase 1 Phase 2

Detailed Description:

This is a double blind, randomized, placebo-controlled, single-dose, three-site trial. The trial is a biomarker-based, integrated Phase 1b/2a clinical trial involving 100 subjects. One group (n=50) will receive placebo, while the other group (n=50) will receive 125 mg of oral saracatinib once daily.

Randomization will be stratified by center. The randomization scheme will be in random blocks of 2 and 4 within each stratum to maintain balance. The study is designed to have interim analysis of the drop-out rates when approximately 30% of the randomized patients have achieved the 24-week assessment. Should the drop-out rate be higher than the 20% that is anticipated, a new sample size calculation will be performed to make sure that the power of the study is maintained at 80% .

Duration of follow-up will be 28 weeks including 24 weeks of treatment with saracatinib or placebo.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: This is a randomized clinical trial, in which the patients and investigators are masked to treatment assignment.
Primary Purpose: Treatment
Official Title: Use of the Src Family Kinase Inhibitor Saracatinib in the Treatment of Idiopathic Pulmonary Fibrosis
Actual Study Start Date : November 12, 2020
Estimated Primary Completion Date : September 28, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Active Comparator: Saracatinab
saracatinib 125 mg once daily by mouth for 24 weeks
Drug: Saracatinab
125 mg once daily by mouth for 24 weeks

Placebo Comparator: Placebo
matching placebo once daily by mouth for 24 weeks
Drug: Placebo
once daily by mouth for 24 weeks




Primary Outcome Measures :
  1. Safety of saracatinib in IPF as measured by frequency of adverse events [ Time Frame: 24 weeks ]
    Safety data will be listed and summarized with patient counts and percentages in each treatment arm

  2. Tolerability of saracatinib in IPF as measured by Severity of adverse events [ Time Frame: 24 weeks ]
    A listing of all adverse eventsw by patient will be presented. This listing will include patient number, adverse event (actual term and preferred term), event stand and end dates, CTCAE grade, relationship to the study drug/procedure, seriousness and outcome. A listing of SAEs will be produced using the similar format. This is not a scale. It is a data capture tool.

  3. Pharmacokinetics of saracatinib in IPF as measured by serum levels [ Time Frame: 24 weeks ]
    Serum levels of saracatinib

  4. Pharmacodynamics of saracatinib in IPF as measured by change in serum β-CTX [ Time Frame: 24 weeks ]
    Change in serum β-CTX as a Src kinase dependent biomarker

  5. Efficacy of saracatinib in IPF as measured by change in FVC [ Time Frame: 24 weeks ]
    Change in FVC from baseline


Secondary Outcome Measures :
  1. Efficacy of saracatinib in IPF (HRCT) [ Time Frame: 24 weeks ]
    Change in HRCT quantitative analysis of the extent of pulmonary fibrosis. The analysis pf HRCT data will involve data-driven texture analysis (DTA), a machine learning method capable of automatic detection and quantification of lung fibrosis on HRCT

  2. Efficacy of saracatinib in IPF (DLCO) as measured by change in DLCO [ Time Frame: 24 weeks ]
    Change in diffusing capacity of the lung for carbon monoxide (DLCO)

  3. Efficacy of saracatinib in IPF (exacerbations) as measured in time to first acute exacerbation [ Time Frame: 24 weeks ]
    Time to the first acute exacerbation

  4. Efficacy of saracatinib in quality of life in IPF (SGRQ) as measured by total score on SGRQ questionnaire [ Time Frame: 24 weeks ]
    Total score on the SGRQ questionnaire. St. George's Respiratory Questionnaire (SGRQ) is a 50-item, self-administered, respiratory-specific questionnaire with items covering three domains: symptoms, activities, impacts. Each domain and a total score range from 0-100, with higher scores connoting greater impairment.

  5. Efficacy of saracatinib in quality of life in IPF (L-IPF) as measured by total score on L-IPF questionnaire [ Time Frame: 24 weeks ]
    Total score on the L-IPF questionnaire. Living with IPF (L-IPF) is an IPF-specific questionnaire whose 43 items cover two modules: symptoms and impacts. A model-based scoring algorithm has been developed via psychometric methods.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. IPF of any duration, confirmed or diagnosed by ILD center or expert according to Fleischner Guidelines (33)
  2. Women or men >40 years of age at the time of screening
  3. FVC%>45% of predicted value (GLI-2012)
  4. Single breath DLCO% 30 - 79 inclusive of predicted (without bronchodilator and uncorrected for hemoglobin)
  5. FEV1/FVC>70 (GLI-2012)
  6. Provision of signed/dated written informed consent prior to any study-specific procedures
  7. Females must be of nonchildbearing potential (defined as surgically sterilized [ie, bilateral tubal ligation, bilateral oophorectomy or complete hysterectomy] or postmenopausal [defined as 12 months with no menses without an alternative medical cause] with a follicle-stimulating hormone [FSH] > 25.8 IU/L) or use a highly effective method of contraception (defined as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; progestogen only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of drug/matching placebo
  8. Male subjects must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (fr om the time they sign consent) and for 3 months after the last dose of drug/matching placebo to prevent pregnancy in a partner. Male subjects must not donate or bank sperm for the duration of the study (from the time they sign consent) and for 3 months after the last dose of drug/matching placebo.

Exclusion Criteria:

  1. Requirement for supplemental oxygen > 4 L/min at rest to maintain saturation > 90%
  2. Active infection at screening or randomization
  3. Known active or latent hepatitis B or C
  4. Life expectancy for disease other than IPF < 2.5 years (Investigator assessment)
  5. Listed for lung transplantation
  6. Taking pirfenidone or nintedanib in the last 4 weeks
  7. Pregnancy or lactation
  8. Known allergic reactions to components of saracatinib
  9. Treatment with another investigational drug or other intervention within 8 weeks
  10. Current smoker or tobacco use within 4 months
  11. Major surgery within the past 2 months
  12. Advanced hematologic, renal, hepatic, any lung disease determined by the investigator to be non-IPF related or metabolic disease that, in the opinion of the investigator, would make it unsafe for the person to receive study drug.
  13. Previous lung transplantation
  14. Inability to attend scheduled study visits
  15. Inability to give informed consent
  16. Inability to perform pulmonary function testing
  17. History of malignancy in the past two years, other than squamous or basal cell skin cancer
  18. Previous acute exacerbation of IPF requiring hospitalization and/or antibiotics within 90 days before the first dose of the investigational product
  19. Liver function test results ≥3× upper limit of normal (ULN) liver isoform of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), or alkaline phosphatase (ALP) or ≥2×ULN total bilirubin (excepting documentation of benign hereditary cause). An isolated total bilibrubin elevation (ie, no significant concomitant elevation in ALT or AST) at baseline of ≤ 2xULN is permitted. If there is concomitant elevation in ALT or AST to ≤3xULN, then the threshold for total bilirubrin is ≤1.5xULN.
  20. Creatinine clearance <30 mL/min calculated by Cockcroft-Gault formula
  21. Known pulmonary hypertension (PH) requiring PH-specific treatment
  22. Chronic oral corticosteroids at doses greater than prednisone 10 mg/day (or equivalent)
  23. Refer to 6.5 Concomitant Therapy for exclusions based on co-medications

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): NCT04598919


Contacts
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Contact: Emily Kinzel, MS 212-659-6856 emily.kinzel@mountsinai.org
Contact: Ellen G Moquete, MSH (212) 659-9651 ellen.moquete@mountsinai.org

Locations
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United States, Colorado
National Jewish Health Recruiting
Denver, Colorado, United States, 80206
Contact: Kaitlin Fier    303-270-2852    fierk@njhealth.org   
Contact: Kris Eliopoulos, RN    303-398-2622    eliopoulosk@njhealth.org   
Principal Investigator: Gregory Downey, MD         
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06510
Contact: Maksyn Minasyan    203-785-4177    ildinfo@yale.edu   
Contact: Louise McLellan, RN    203-785-4177    ildinfo@yale.edu   
Principal Investigator: Naftali Kaminski, MD         
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Shanti Mangar    646-320-5303    shanti.mangar@mssm.edu   
Principal Investigator: Maria Padilla         
Sponsors and Collaborators
National Jewish Health
Yale University
Icahn School of Medicine at Mount Sinai
AstraZeneca
National Center for Advancing Translational Science (NCATS)
Investigators
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Principal Investigator: Gregory Downey, MD National Jewish Health
Principal Investigator: Annetine C Gelijns, PhD Icahn School of Medicine at Mount Sinai
Principal Investigator: Naftali Kaminski, MD Yale University
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Responsible Party: National Jewish Health
ClinicalTrials.gov Identifier: NCT04598919    
Other Study ID Numbers: 5UH3TR002445 ( U.S. NIH Grant/Contract )
UG3TR002445 ( U.S. NIH Grant/Contract )
First Posted: October 22, 2020    Key Record Dates
Last Update Posted: February 9, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All of the individual participant data collected during the trial, after deidentification.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Immediately following publication. No end date.
Access Criteria: Anyone who wishes to access the data for any analysis purpose. After the study is completed, the de-identified, archived data will be transmitted to and stored at a publicly available data repository, for use by other researchers including those outside of the study.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Jewish Health:
Idiopathic Pulmonary Fibrosis
Scarring of the lung
Saracatinib
randomized controlled trial
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