Venetoclax for Idiopathic Pulmonary Fibrosis

No longer recruiting at 2 trial locations

Overseen By Steven R Duncan, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Malignancy, Acute infection, Severe cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Venetoclax as a potential treatment for idiopathic pulmonary fibrosis (IPF), a lung disease where tissue thickens and scars over time. Researchers aim to determine if Venetoclax can help by targeting specific lung cells and reducing scarring. This trial may suit individuals diagnosed with IPF in the last five years who can perform daily tasks with some difficulty due to lung capacity. If successful, Venetoclax might offer new hope for those living with this challenging condition. As an Early Phase 1 trial, this research focuses on understanding how Venetoclax works in people, offering participants a chance to be among the first to receive this potential treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications that are potent CYP3A4 inhibitors or inducers during the 24-week treatment period. This includes drugs like ritonavir, ketoconazole, and rifampin, among others.

Is there any evidence suggesting that Venetoclax is likely to be safe for humans?

Research has shown that Venetoclax, also known as ABT-199, has been safely used in patients with chronic lymphocytic leukemia. These patients have tolerated it well, suggesting the drug is generally safe for humans.

In early studies, Venetoclax effectively treated idiopathic pulmonary fibrosis (IPF) by helping certain immune cells die, which can reduce lung scarring. However, this trial is among the first to test Venetoclax specifically for IPF.

Since this study is in an early phase, researchers are primarily focused on assessing the drug's safety for people with IPF. This step is crucial to ensure the treatment's safety before conducting larger studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IPF?

Unlike the standard of care for idiopathic pulmonary fibrosis, which typically includes antifibrotic drugs like pirfenidone and nintedanib, Venetoclax works differently by targeting and inhibiting a protein called BCL-2. BCL-2 plays a role in the survival of cells, and by blocking it, Venetoclax may help reduce the excessive cell survival and fibrosis seen in this condition. Researchers are excited about Venetoclax because it offers a novel mechanism of action that could potentially alter the course of the disease more effectively than existing treatments.

What evidence suggests that Venetoclax might be an effective treatment for idiopathic pulmonary fibrosis?

Research has shown that Venetoclax, also known as ABT-199, might help treat idiopathic pulmonary fibrosis (IPF). In early studies, Venetoclax prompted certain immune cells called macrophages to die off naturally, reducing lung scarring. People with IPF have high levels of a protein called Bcl-2 in their macrophages, which prevents these cells from dying as they should. Venetoclax blocks Bcl-2, allowing these cells to die and possibly reducing lung scarring. Venetoclax has also proven safe and effective for treating chronic lymphocytic leukemia, suggesting it could be safe for IPF patients too. This treatment is important because no cure currently exists for IPF. Participants in this trial will receive Venetoclax 100 mg daily for 3 weeks to evaluate its effects on IPF. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 40-85 with a confirmed diagnosis of idiopathic pulmonary fibrosis (IPF) that's been known for less than 5 years and have at least moderate lung function. Participants must be able to consent, follow the study plan, and not be on certain other drugs or have major health issues like severe liver problems, heart conditions, recent infections, kidney disease requiring dialysis, or a history of cancer in the last 5 years.

Inclusion Criteria

You can breathe out a lot of air compared to what is expected for someone your size.

I have been diagnosed with idiopathic pulmonary fibrosis.

Ability and willingness to give informed consent and adhere to study requirements

Exclusion Criteria

I am a man who agrees to use contraception or remain abstinent and not donate sperm during and 90 days after the study.

I have not had a severe heart issue or stroke in the last 3 months.

I do not have untreated heart rhythm problems or a family history of long QT syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Venetoclax 100 mg daily for 3 weeks

3 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Venetoclax

Trial Overview The trial tests Venetoclax's safety and effectiveness in treating IPF. Researchers believe it may help by causing problematic cells in the lungs to self-destruct. The drug has worked well before in leukemia patients without serious side effects.

How Is the Trial Designed?

Group I: treatment Experimental Treatment 1 Intervention

Venetoclax 100 mg daily for 3 weeks

Venetoclax is already approved in United States, European Union for the following indications:

Approved in United States as Venclexta for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Approved in European Union as Venclyxto for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)
• Acute myeloid leukemia (AML)

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

The combination of venetoclax with bendamustine-rituximab (BR) was found to be safe and tolerable in a study of 60 patients with relapsed/refractory non-Hodgkin's lymphoma, with the recommended phase II dose established at 800 mg daily.

The overall response rate to the treatment was 65%, with a median duration of response of 38.3 months, indicating preliminary efficacy for this combination therapy in managing B-cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study. de Vos, S., Swinnen, LJ., Wang, D., et al.[2021]

Citations

1. withpower.com withpower.com/trial/early-phase-1-pulmonary-fibrosis-8-2023-0e717

Venetoclax for Idiopathic Pulmonary Fibrosis This trial is testing ABT-199, a drug that helps certain immune cells die, in patients with idiopathic pulmonary fibrosis (IPF).

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05976217/safety-and-efficacy-of-venetoclax-in-idiopathic-pulmonary-fibrosis

Safety and Efficacy of Venetoclax in Idiopathic Pulmonary ... ABT-199 (Venetoclax), showed marked efficacy in preclinical models of IPF by inducing apoptosis of MDMs and reversing established fibrosis.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12102415/

Idiopathic Pulmonary Fibrosis, Today and Tomorrow Secondary outcomes are data about the pharmacokinetics of the molecule under study, relative change in FVC (ml), percentage change in FVC, absolute and relative ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772558825000052

Advances in idiopathic pulmonary fibrosis diagnosis and ... ABT-199 (venetoclax): Macrophages from IPF patients have increased expression of B-cell lymphoma-2 (Bcl-2) in mitochondria. In mice exposed to bleomycin, a ...

5. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05976217?keyword=%22Apoptosis%22

Safety and Efficacy of Venetoclax in Idiopathic Pulmonary ... ABT-199 has shown therapeutic efficacy and good safety and tolerability in patients with chronic lymphocytic leukemia. Investigators anticipate that treatment ...

6. facebook.com facebook.com/groups/165298933916143/posts/1833651573747529/

Note: the drug used in this trial has been used ... ABT-199 has shown therapeutic efficacy and good safety and tolerability in patients with chronic lymphocytic leukemia. Investigators anticipate that treatment ...