Saracatinib in the Treatment of Idiopathic Pulmonary Fibrosis

NCT04598919 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 5UH3TR002445UG3TR002445
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 4

Brief Summary

Scarring of the lung, termed pulmonary fibrosis (PF), is a chronic, progressive, and usually fatal disorder. While two anti-fibrotic drugs have 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

Conditions

Idiopathic Pulmonary Fibrosis (IPF)

Keywords

Idiopathic Pulmonary Fibrosis; Scarring of the lung; Saracatinib; randomized controlled trial

Outcome Measures

Primary Outcomes (5)

• Safety of saracatinib in IPF as measured by frequency of adverse events

  Safety data will be listed and summarized with patient counts and percentages in each treatment arm

  24 weeks

• Tolerability of saracatinib in IPF as measured by Severity of adverse events

  A listing of all adverse events 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.

  24 weeks

• Pharmacokinetics of saracatinib in IPF as measured by serum levels

  Serum levels of saracatinib

  24 weeks

• Pharmacodynamics of saracatinib in IPF as measured by change in serum β-CTX

  Change in serum β-CTX as a Src kinase dependent biomarker

  24 weeks

• Efficacy of saracatinib in IPF as measured by change in FVC

  Change in FVC from baseline

  24 weeks

Secondary Outcomes (5)

• Efficacy of saracatinib in IPF (HRCT)

  24 weeks

• Efficacy of saracatinib in IPF (DLCO) as measured by change in DLCO

  24 weeks

• Efficacy of saracatinib in IPF (exacerbations) as measured in time to first acute exacerbation

  24 weeks

• Efficacy of saracatinib in quality of life in IPF (SGRQ) as measured by total score on SGRQ questionnaire

  24 weeks

• Efficacy of saracatinib in quality of life in IPF (L-IPF) as measured by total score on L-IPF questionnaire

  24 weeks

Study Arms (2)

Saracatinab

ACTIVE COMPARATOR

saracatinib 125 mg once daily by mouth for 24 weeks

Drug: Saracatinab

Placebo

PLACEBO COMPARATOR

matching placebo once daily by mouth for 24 weeks

Drug: Placebo

Interventions

Saracatinab DRUG

125 mg once daily by mouth for 24 weeks

Saracatinab

Placebo DRUG

once daily by mouth for 24 weeks

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IPF of any duration, confirmed or diagnosed by ILD center or expert according to Fleischner Guidelines (33). Subjects with a probable or indeterminant CT scan who otherwise meet the Fleischner criteria for IPF are eligible to be included in the study after a multidisciplinary evaluation. A positive Envisia genomic classifier score (34) on a lung biopsy specimen will be considered as strong evidence for a diagnosis of IPF. Subjects with a positive invisia genomic classifier score in conjunction with a probable or indeterminant CT scan are eligible to be included in the study after a multidisciplinary evaluation.
• Women or men \>40 years of age at the time of screening
• FVC%\>45% of predicted value (GLI-2012)
• Single breath DLCO% ≥ 30 - inclusive of predicted (without bronchodilator and uncorrected for hemoglobin GLI-2017)
• FEV1/FVC\>70 (GLI-2012)
• Provision of signed/dated written informed consent prior to any study-specific procedures
• Females must be of nonchildbearing potential (defined as surgically sterilized \[i.e., bilateral tubal ligation, bilateral oophorectomy or complete hysterectomy\] 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
• 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 (from 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.

You may not qualify if:

• Requirement for supplemental oxygen \> 4 L/min at rest to maintain saturation \> 90%
• Active infection at screening or randomization
• Known active or latent hepatitis B or C
• Life expectancy for disease other than IPF \< 2.5 years (Investigator assessment)
• Listed for lung transplantation
• Taking pirfenidone or nintedanib in the last 4 weeks
• Pregnancy or lactation
• Known allergic reactions to components of saracatinib
• Treatment with another investigational drug or other intervention within 8 weeks
• Current smoker or tobacco use within 4 months
• Major surgery within the past 2 months
• 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.
• Previous lung transplantation
• Inability to attend scheduled study visits
• Inability to give informed consent

Sponsors & Collaborators

• National Jewish Health: lead
• Yale University: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• AstraZeneca: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Baylor University: collaborator
• International Center for Health Outcomes and Innovation Research: collaborator

Study Sites (4)

National Jewish Health

Denver, Colorado, 80206, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Baylor University Medical Center (BUMC)

Dallas, Texas, 75246, United States

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Gregory Downey, MD

  National Jewish Health

  PRINCIPAL INVESTIGATOR

• Maria Padilla, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Danielle Antin-Ozerkis, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Susan Mathai, MD

  Baylor University Medical Center (BUMC)

  PRINCIPAL INVESTIGATOR

• Annetine Gelijns, PhD

  Data and Clinical Coordinating Center- InCHOIR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a randomized clinical trial, in which the patients and investigators are masked to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a randomized (8:1 ratio), double blind, parallel design, placebo controlled trial.

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: October 22, 2020
• Study Start: November 12, 2020
• Primary Completion: September 15, 2024
• Study Completion: June 30, 2025
• Last Updated: November 14, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (4)