Acebilustat for Arm Lymphedema

(HEAL Trial)

Overseen By Osama Alnahar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: NSAIDs, Immunosuppressants, Statins, others

Disqualifiers: Cancer, Kidney disease, Liver disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how acebilustat can help individuals with lymphedema in one arm. Lymphedema causes fluid buildup and swelling, often after surgery or other treatments. Participants will take acebilustat and a placebo (a pill with no active drug) over nine months to determine if the drug reduces swelling. It is suitable for those who have had arm lymphedema for more than six months and regularly wear a compression garment. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. Specifically, you must stop using non-steroidal anti-inflammatory drugs (like ibuprofen), immunosuppressive drugs, leukotriene pathway inhibitors, and statin drugs. Statin drugs should be discontinued at least 2 weeks before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that acebilustat, the treatment under study for arm lymphedema, is generally well-tolerated. Acebilustat reduces inflammation, which may relieve symptoms like swelling.

In previous studies, participants taking acebilustat did not experience major safety issues. Some mild side effects occurred, but they were not serious.

Overall, acebilustat has demonstrated a good safety record based on past research. However, further studies are needed to fully understand its effects on lymphedema. ^{1 2 3 4 5}

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

Unlike the standard treatments for arm lymphedema, which often involve physical therapy, compression garments, or surgery, acebilustat offers a novel approach by targeting inflammation directly. Researchers are excited about acebilustat because it works by inhibiting a specific enzyme called LTA4H, which plays a crucial role in the inflammatory process. This mechanism is different from existing treatments and could potentially reduce swelling more effectively and with fewer side effects. If successful, acebilustat might offer a less invasive and more convenient option for patients, significantly improving their quality of life.

What evidence suggests that acebilustat might be an effective treatment for arm lymphedema?

Research suggests that acebilustat, one of the treatments in this trial, might help with arm lymphedema by reducing swelling. In studies on other conditions, acebilustat has shown promise in lowering inflammation, which is important because lymphedema often involves swelling caused by inflammation. Acebilustat blocks a chemical called leukotriene B4, which plays a major role in causing inflammation. Although limited studies have focused directly on arm lymphedema, the drug's overall ability to reduce inflammation suggests it could be helpful. Early results from patients with similar conditions have been encouraging, showing reduced symptoms and swelling. ^{1 2 4 6 7}

Who Is on the Research Team?

Stanley Rockson, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with stage 2 upper arm lymphedema lasting over 6 months. Participants must have completed lymphedema therapy at least 8 weeks prior, be vaccinated against COVID-19, and use compression garments. They can't join if they have clotting disorders, chronic infections in the limb, kidney or liver disease, are pregnant/nursing, have a history of substance abuse within the last six months or are on certain medications like statins.

Inclusion Criteria

Ability to understand and sign informed consent document

I am willing to keep a consistent self-care routine.

I finished my lymphedema treatment more than 8 weeks ago.

Exclusion Criteria

Any reason precluding full participation in the study

Substance abuse within 6 months prior to screening

I or my family have a history of prolonged QT syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-7 days

1 visit (in-person)

Treatment

Participants receive oral placebo and acebilustat for 9 months, with 3 months on placebo and 6 months on acebilustat

36 weeks

4 visits (in-person, approximately every 90 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acebilustat
• Placebo

Trial Overview The study tests Acebilustat's effectiveness for treating unilateral upper extremity lymphedema compared to a placebo. Over nine months, participants will unknowingly receive either Acebilustat or a placebo for different durations (placebo for three months and Acebilustat for six).

How Is the Trial Designed?

Group I: Placebo and acebilustat Experimental Treatment 2 Interventions

Participants will take acebilustat and placebo over a period of 9 months.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Celltaxis LLC

Collaborator

Trials

1

Recruited

40+

Published Research Related to This Trial

A 78-year-old woman with severe angioedema caused by ACE inhibitors did not respond to standard treatments but was successfully treated with icatibant, a drug typically used for hereditary angioedema.

This case suggests that icatibant may be effective for ACE-i induced angioedema due to its mechanism of blocking bradykinin B2 receptors, highlighting the need for further randomized controlled trials to confirm its efficacy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Icatibant is a new treatment option in life-threatening angioedema triggered by angiotensin-converting enzyme inhibitor]. Fast, S., Henningsen, E., Bygum, A.[2011]

The retrospective examination of icatibant, a bradykinin B2 receptor antagonist, revealed variability in patient responses and limited efficacy of adrenaline for treating angioedema.

The study emphasizes the urgent need for biomarkers to differentiate between histaminergic and non-histaminergic angioedema, as well as guidelines to enhance the effectiveness of icatibant in non-hereditary cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world off-label use of icatibant for acute management of non-hereditary angioedema. Le, TA., Smith, W., Hissaria, P.[2021]

Icatibant is a safe and effective treatment for acute attacks of hereditary angioedema in adults, with clinical evidence supporting its use and only 10% of patients needing a second dose.

The most common side effects are mild and localized, such as pain and swelling at the injection site, and no serious adverse reactions have been reported, making it a favorable option for self-administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence-based review of the potential role of icatibant in the treatment of acute attacks in hereditary angioedema type I and II. Floccard, B., Hautin, E., Bouillet, L., et al.[2021]

Icatibant, a bradykinin B2 receptor antagonist, has been shown to be effective in treating angioedema caused by angiotensin-converting enzyme inhibitors, although it is currently used off-label in emergency situations.

Corticosteroids and antihistamines are ineffective for this type of angioedema, highlighting the need for further research, particularly a double-blind study, to confirm the effectiveness of C1-esterase-inhibitor in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Angiotensin-Converting-Enzyme-Induced Angioedema. Bas, M.[2017]

In cases of acute angioedema that do not respond to standard antihistamine treatments, such as when bradykinin is involved instead of histamine, alternative therapies like the beta2 receptor antagonist icatibant may provide relief, as demonstrated in a reported case where the patient experienced improvement within 20 minutes.

Although icatibant is officially approved only for hereditary angioedema, its off-label use in other types of angioedema can be justified in life-threatening situations, highlighting the need for flexibility in treatment options when standard therapies fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with icatibant in the management of drug induced angioedema. Bertazzoni, G., Bresciani, E., Cipollone, L., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05203835

Trial of Acebilustat for the Treatment of Upper Arm ... See Delay Results Type in the Results Data ... A Pilot Placebo-Controlled Trial of Acebilustat (CTX-4430) for the Treatment of Human Upper Extremity Lymphedema.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10517095/

Evaluation of Acebilustat, a Selective Inhibitor ... Acebilustat, a leukotriene B4 inhibitor, has potential to reduce inflammation and symptom duration. Methods. In a single-center trial spanning Delta and Omicron ...

3. researchgate.net researchgate.net/publication/369656269_Evaluation_of_acebilustat_a_selective_inhibitor_of_leukotriene_B4_biosynthesis_for_treatment_of_outpatients_with_mild-moderate_COVID-19_disease_A_randomized_double-blind_placebo-_controlled_Phase_2_tr

Evaluation of acebilustat, a selective inhibitor of leukotriene ... Acebilustat, a leukotriene B4 (LTB4) inhibitor, has potential to reduce inflammation and symptom duration. Methods: In a single-center trial ...

4. clinicaltrials.gov clinicaltrials.gov/search?intr=ACEBILUSTAT&aggFilters=studyType:int&viewType=Table&rank=2

Search for: ACEBILUSTAT, Interventional studies These trials gather additional information about a drug's safety, efficacy, or optimal use. ... Trial of Acebilustat for the Treatment of Upper Arm Lymphedema.

5. guidetopharmacology.org guidetopharmacology.org/GRAC/LigandDisplayForward?tab=clinical&ligandId=11984

acebilustat | Ligand page Acebilustat (CTX-4430) has been evaluated for clinical anti-inflammatory activity in lung inflammation (including in cystic fibrosis patients) and in acne ...

6. stanfordhealthcare.org stanfordhealthcare.org/trials/t/NCT05203835.html

Trial of Acebilustat for the Treatment of Upper Arm ... This study is designed to investigate the response of unilateral upper extremity (arm) lymphedema, during pharmacologic treatment of lymphedema with oral ...

7. trial.medpath.com trial.medpath.com/drug/72da8a72bc37ab77/acebilustat

Acebilustat | MedPath Acebilustat is under investigation in clinical trial NCT01748838 (Phase 1 Study Assessing the Safety and Tolerability of CTX-4430). Indication. No indication ...