Safety and Efficacy of Venetoclax in Idiopathic Pulmonary Fibrosis

March 27, 2024 updated by: A. Brent Carter, MD, University of Alabama at Birmingham
Based on preclinical data, investigators hypothesize that apoptosis resistance in monocyte-derived macrophages (MDMs) have a decisive role in the development of idiopathic pulmonary fibrosis (IPF). Specifically, macrophages from subjects with IPF have increased expression of Bcl-2 in mitochondria. In preclinical models of IPF, a conditional deletion of Bcl-2 in MDMs reverses established fibrosis by inducing apoptosis. Additional evidence to suggest that Bcl-2 expression in MDM mitochondria is a therapeutic target for IPF as administration of the Bcl-2 inhibitor, ABT-199 (Venetoclax), showed marked efficacy in preclinical models of IPF by inducing apoptosis of MDMs and reversing established fibrosis. ABT-199 is an orally available mimetic of the BH3 domain of Bcl-2, which is the domain the anchors Bcl-2 in the mitochondria to inhibit apoptosis. ABT-199 has shown therapeutic efficacy and good safety and tolerability in patients with chronic lymphocytic leukemia. Investigators anticipate that treatment with ABT-199 could result in significant benefit for IPF patients that have a life expectancy of 3-5 years. As there is no curative therapy for IPF, this clinical trial has the potential to substantially alter treatment approaches in patients with IPF.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: A. Brent Carter, MD
  • Phone Number: (205) 934-5018
  • Email: BCARTER1@UAB.EDU

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • UAB
      • Birmingham, Alabama, United States, 35214
        • TKC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age between 40-85 years old, male and female.
  2. A diagnosis of IPF that fulfills current ATS/ERS Consensus Criteria (1).
  3. IPF duration <5 years, based on the date of definitive diagnosis.
  4. Ability and willingness to give informed consent and adhere to study requirements.
  5. Forced Vital Capacity (FVC) > 50% predicted values.

Exclusion Criteria:

  1. Diagnosis of major comorbidities expected to interfere with study participation.
  2. History of malignancy within the last 5 years, excluding basal or squamous cell skin cancer.
  3. The occurrence of any acute infection requiring systemic antibiotic therapy within 2 weeks prior to Screening (Visit 1).
  4. Treatment for >14 days within the preceding month with >20 mg. prednisone (or equivalent) or any treatment during the last month with a cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, calcineurin inhibitors, azathioprine, etc.), given increased risks of opportunistic infections.
  5. Concurrent participation in other experimental trials.
  6. Fertile women who do not agree to abstinence or an effective form of contraception (as approved by the investigator), or who are breast feeding, for 4 weeks before randomization until 90 days after the last administration of study medication (or placebo).
  7. Men who are not surgically sterile and do not agree to remain abstinent from heterosexual intercourse or use effective contraception (as approved by the investigator), and refrain from donating sperm, from the time of giving informed consent until 90 days after the last administration of study medication (or placebo).
  8. Subjects with known hypersensitivity to capsule "bulking" agents.
  9. A history of bone marrow disorder including aplastic anemia, or marked anemia defined as hemoglobin < 10.0 g/dL (or 6.2 mmol/L).
  10. Severe cardiovascular disease, defined as any of the following within the preceding 12 weeks: acute myocardial infarction or unstable angina, a coronary revascularization procedure, congestive heart failure (NYHA Class III or IV), or stroke, including a transient ischemic attack.
  11. Evidence of cardiac conducting abnormalities, defined as second- or third-degree AV block not successfully treated with a pacemaker, or a personal or family history of long QT syndrome (QTc interval >450 msec for males or 470 msec for females).
  12. End-stage renal disease requiring dialysis.
  13. Undergoing transplantation evaluation or listed with the United Network for Organ Sharing (UNOS) as a lung transplantation candidate at the time of enrollment in this trial.
  14. Liver function tests (transaminases, alkaline phosphatase, direct and total bilirubin) >2x upper limit of normal values.
  15. Systemically administered potent CYP3A4 inhibitors or inducers are prohibited during the 24-week treatment period.

Inhibitors include: pirfenidone, boceprevir, cobicistat, conivaptan, ritonavir, itraconazole, ketoconazole, telaprevir, troleandomycin, voriconazole, clarithromycin, diltiazem, idelalisib, nefazodone, nelfinavir.

Inducers include: carbamazepine, enzalutamide, mitotane, phenytoin, rifampin.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: treatment
Venetoclax 100 mg daily for 3 weeks
Drug: Venetoclax
100 mg daily by mouth for 3 weeks This drug inhibits a protein (Bcl-2) that protects cells from undergoing programmed cell death.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with treatment-related adverse events as assessed by measuring liver function.
Time Frame: 3 weeks
complete metabolic panel
3 weeks
Number of participants with treatment-related adverse events as assessed by measuring blood counts.
Time Frame: 3 weeks
complete blood count
3 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of monocyte-derived macrophages that undergoing apoptosis.
Time Frame: 3 weeks
flow cytometry
3 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 18, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 20, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 26, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 28, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB-300010757

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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