Panobinostat for Sickle Cell Disease

(LBH589 Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abdullah Kutlar

Must not be taking: Hydroxyurea, Butyrates, Decitabine, others

Disqualifiers: Recent vaso-occlusive crisis, Cardiac diseases, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if panobinostat is safe and effective for adults with sickle cell disease. Researchers believe panobinostat may help by boosting hemoglobin F, which can improve sickle cell symptoms, and by reducing inflammation, a significant issue for those with this condition. Ideal participants have sickle cell disease, do not respond well to standard treatments like hydroxyurea, and have experienced frequent hospitalizations or severe pain crises. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop using certain medications that can induce Hb F, such as hydroxyurea, at least 60 days before starting the study. If you are on any prohibited medications, you must either discontinue them or switch to a different medication before enrolling.

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

Research has shown that panobinostat has been studied for its safety in people with sickle cell disease. As an HDAC inhibitor, panobinostat has shown promise in helping with sickle cell disease by increasing hemoglobin F and reducing inflammation. While this trial phase focuses on safety, specific data from earlier studies are not mentioned here.

Panobinostat is currently under investigation in an early phase of clinical research. This phase typically involves a smaller group of participants and primarily examines the drug's safety and tolerability. Researchers are still learning about its safety due to its early phase.

It is important to note that panobinostat is already approved for treating other conditions, which might suggest some level of safety, but its effects can vary depending on the condition. Participants should discuss the possible risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Unlike standard treatments for sickle cell disease, which often focus on managing symptoms and preventing complications through medications like hydroxyurea or blood transfusions, Panobinostat offers a novel approach. Panobinostat is a histone deacetylase inhibitor, which means it works by modifying the way DNA is packaged in cells, potentially reactivating fetal hemoglobin production. This could directly address the underlying cause of sickle cell disease by increasing the proportion of healthy, non-sickling red blood cells. Researchers are excited about this treatment because it targets the disease at a genetic level, offering hope for a more effective and transformative therapy.

What evidence suggests that panobinostat might be an effective treatment for sickle cell disease?

Research has shown that panobinostat, a type of drug, can significantly increase hemoglobin F levels. Higher levels of hemoglobin F improve health outcomes for people with sickle cell disease. This drug also reduces inflammation, a major cause of pain and other issues in sickle cell disease. These effects suggest that panobinostat might effectively manage and improve the symptoms of sickle cell disease. Participants in this trial will receive panobinostat to evaluate its effectiveness in this context. ^{2 4 5 6 7}

Who Is on the Research Team?

Abdullah Kutlar, MD

Principal Investigator

Augusta University

Are You a Good Fit for This Trial?

Adults over 18 with sickle cell disease who haven't responded well to or can't take hydroxyurea. They should have had at least two hospitalizations or three pain crises in the past year, or a history of other severe complications related to sickle cell disease. People with certain blood counts, organ dysfunctions, heart conditions, active infections like HIV/Hepatitis B/C, recent surgeries, and women who are pregnant/breastfeeding or not using contraception are excluded.

Inclusion Criteria

I have been diagnosed with SS or S-β0 Thalassemia.

I have needed treatment for a prolonged erection in the last two years.

I cannot tolerate or have not responded to hydroxyurea treatment.

Exclusion Criteria

I have a condition that affects my heart's rhythm.

I cannot stop or change my current medication for the study.

- Albumin <3.0 g/dl

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive escalating doses of panobinostat to determine safety and tolerability over a 12-week period

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Panobinostat

Trial Overview

The trial is testing panobinostat's safety and effectiveness for adults with sickle cell disease. Panobinostat is an HDAC inhibitor that may increase hemoglobin F levels and reduce inflammation—both potentially beneficial for managing this condition.

How Is the Trial Designed?

Group I: Panobinostat Experimental Treatment 1 Intervention

All patients will receive Panobinostat at specified dose levels and dosing schedules.

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

Approved in United States as Farydak for:

• Multiple myeloma

Approved in European Union as Farydak for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Abdullah Kutlar

Lead Sponsor

Trials

1

Recruited

20+

Secura Bio, Inc.

Industry Sponsor

Trials

9

Recruited

200+

Published Research Related to This Trial

Panobinostat, a histone deacetylase inhibitor for treating relapsed multiple myeloma, primarily undergoes metabolism through the CYP3A4 enzyme, which is crucial for understanding its drug interactions and dosing.

Physiologically based pharmacokinetic (PBPK) modeling predicted that the presence of rifampin, a strong CYP3A4 inducer, could significantly reduce panobinostat exposure by 65%, while its absorption is not affected by changes in stomach pH, leading to important dosing recommendations for clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologically Based Pharmacokinetic Model Predictions of Panobinostat (LBH589) as a Victim and Perpetrator of Drug-Drug Interactions. Einolf, HJ., Lin, W., Won, CS., et al.[2018]

Panobinostat (Farydak(®)) is an HDAC inhibitor that has been approved in the US for use in combination with bortezomib and dexamethasone to treat recurrent multiple myeloma in patients who have undergone at least two prior treatments.

The drug is currently being explored in clinical trials for various hematological and solid tumors, indicating its potential as a versatile cancer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panobinostat: first global approval. Garnock-Jones, KP.[2018]

In a study involving 36 patients with advanced cancer, food intake was found to have a minor effect on the oral bioavailability of panobinostat, a novel anti-cancer drug, with systemic exposure reduced by 14-16% after meals.

Panobinostat was well tolerated among patients, showing common side effects like thrombocytopenia and fatigue, and demonstrated antitumor activity, with one patient achieving a partial response and six maintaining stable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of food on the bioavailability of panobinostat, an orally active pan-histone deacetylase inhibitor, in patients with advanced cancer. Shapiro, GI., Frank, R., Dandamudi, UB., et al.[2021]

Panobinostat, an oral pan-deacetylase inhibitor, was found to increase the exposure of the CYP2D6 substrate dextromethorphan (DM) by 64% when co-administered, indicating a weak inhibition of CYP2D6 activity in patients with advanced cancer.

Due to this interaction, it is recommended to closely monitor the safety of other medications that are CYP2D6 substrates, especially those with a narrow therapeutic index, when used alongside panobinostat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical investigation of inhibitory effect of panobinostat on CYP2D6 substrate in patients with advanced cancer. Feld, R., Woo, MM., Leighl, N., et al.[2018]

Panobinostat is a potent pan-histone deacetylase (HDAC) inhibitor that promotes the expression of repressed genes, leading to reduced cancer cell growth and increased cell death (apoptosis).

It has shown strong preclinical efficacy at nanomolar concentrations and is being tested in both intravenous and oral forms for various tumor types, indicating its potential as a novel cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of panobinostat and its potential for treatment in solid tumors: an update. Anne, M., Sammartino, D., Barginear, MF., et al.[2023]

Citations

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Panobinostat for Sickle Cell Disease (LBH589 Trial)

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Phase I Study to Determine the Safety and Tolerability of ...

The purpose of this study is to test the safety and efficacy of escalating doses of panobinostat in sickle cell disease.

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In 1995, the landmark Multicenter Study of Hydroxyurea in Adult Sickle Cell Anemia (MSH) trial demonstrated HU's effectiveness in preventing painful crises by ...

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clinicaltrials.gov/study/NCT01245179

Study of Panobinostat (LBH589) in Patients With Sickle ...

The goal of this clinical research study is to find out about the safety and effects of a drug called panobinostat when given to adults with sickle cell ...

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clinicaltrials.gov/study/NCT01245179?cond=%22Sickle%20Cell-Beta-Thalassemia%20Disease%20Syndrome%22&intr=%22Enzyme%20Inhibitors%22&viewType=Table&rank=1

Study of Panobinostat (LBH589) in Patients With Sickle ...

A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...