Sirolimus for Nosebleeds in HHT

Overseen By Negar Bagheri, BSc MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Unity Health Toronto

Disqualifiers: Unstable illness, Infection, Pregnancy, Immunocompromised, Malignancy, 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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug sirolimus (Rapamune) can safely and effectively reduce nosebleeds in individuals with HHT, a genetic condition affecting blood vessels. Participants will take sirolimus daily for three months, with the study measuring weekly changes in nosebleed duration. It suits those diagnosed with HHT who experience nosebleeds lasting at least 15 minutes each week and have received a COVID-19 vaccine. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

Research has shown that sirolimus is safe and effective for treating blue rubber bleb nevus syndrome, offering some reassurance about its safety. However, for hereditary hemorrhagic telangiectasia (HHT), researchers are still analyzing data from earlier studies to confirm its safety for treating nosebleeds in these patients. As this is a Phase 2 study, the focus is on how well patients tolerate sirolimus and any potential side effects. This phase involves careful monitoring to ensure safety for participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for nosebleeds in HHT, which often include options like laser therapy or anti-angiogenic drugs, sirolimus offers a unique approach by targeting the mTOR pathway. This pathway plays a crucial role in cell growth and blood vessel formation, which is particularly relevant for managing HHT-related nosebleeds. Researchers are excited about sirolimus because its oral administration and potential to precisely regulate blood vessel growth could offer a more targeted and effective treatment, reducing the frequency and severity of nosebleeds for patients.

What evidence suggests that sirolimus might be an effective treatment for nosebleeds in HHT?

Studies have shown that sirolimus can help manage the effects of unusual blood vessel growth, common in people with hereditary hemorrhagic telangiectasia (HHT). This excessive growth often causes frequent nosebleeds. In this trial, participants will take oral sirolimus tablets, which target the involved proteins and may reduce bleeding episodes. Previous patients with similar blood vessel formations experienced improvements with sirolimus. Research suggests it could be a promising option for reducing symptoms in these conditions. ^{1 2 6 7 8}

Who Is on the Research Team?

Marie E Faughnan, MD MSc FRCPC

Principal Investigator

Unity Health Toronto

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Hereditary Hemorrhagic Telangiectasia (HHT) who suffer from moderate to severe nosebleeds lasting at least 15 minutes per week. Participants must have received two COVID-19 vaccine doses and not be pregnant, breastfeeding, or planning pregnancy without effective contraception. They should not have a history of cancer, acute infections, unstable illnesses, high creatinine levels, liver issues twice above normal limits or untreated dyslipidemia.

Inclusion Criteria

I experience nosebleeds lasting over 15 minutes each week.

I have received 2 doses of a COVID-19 vaccine.

I am older than 18 years.

Exclusion Criteria

I have no known allergies or reactions to the study drug.

I am a man and my partner can have children but we are not using effective birth control.

My immune system is weak.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral sirolimus starting at 2 mg once daily, adjusted to maintain blood levels of 6-10 ng/ml for 3 months

12 weeks

Weekly visits for dose adjustment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

Monthly visits for outcome measures and safety monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Sirolimus

Trial Overview The study tests the safety and effectiveness of oral sirolimus in reducing nosebleeds in HHT patients. Participants will take a daily dose of sirolimus to maintain specific blood levels for three months. The impact on nosebleeds will be measured against their situation before the trial using patient-reported outcomes.

How Is the Trial Designed?

Group I: Oral sirolimus tablets Experimental Treatment 1 Intervention

Sirolimus starting dose of 2 mg once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml The first dose will be given at the week 12 visit and participants will be observed for 30 min

Sirolimus is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in European Union as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Canada as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Japan as Rapamune for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05269849

NCT05269849 | Sirolimus for Nosebleeds in HHT This phase II pilot study will provide safety data as the primary outcome, and secondarily, efficacy data, outcome measure data and biological exploratory data, ...

2. bvmc.rarediseasesnetwork.org bvmc.rarediseasesnetwork.org/research-study/6214

6214: Sirolimus for Nosebleeds in HHT: A Phase II Pilot Study Sirolimus has been found to work to prevent the effects of the overactive protein that results in vascular malformations in a HHT. There is considerable ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10206540/

Effective long-term sirolimus treatment in hypoxemia ... Our report implicates sirolimus might be a potential treatment option in persistent hypoxemia mainly due to intrapulmonary right-to-left shunt even small ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1538783622001817

A precision medicine approach to hereditary hemorrhagic ... We provide a case‐based approach to the use of antiangiogenic therapies including bevacizumab and pazopanib for the treatment of bleeding in HHT.

5. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-019-1281-4

Future treatments for hereditary hemorrhagic telangiectasia Regression of cutaneous and gastrointestinal telangiectasia with sirolimus and aspirin in a patient with hereditary hemorrhagic telangiectasia.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6945546/

Future treatments for hereditary hemorrhagic telangiectasia More recently, Sirolimus was reported to be efficient and safe for the treatment of blue rubber bleb nevus syndrome, a rare multifocal ...

7. haematologica.org haematologica.org/article/view/haematol.2024.285809/77671

Integration of genotypic data into clinical trial design and ... NCT05269849 Sirolimus for Nosebleeds in HHT. Recruiting ... treatment of anterior epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT).

8. ashpublications.org ashpublications.org/blood/article/144/9/940/516493/How-I-treat-bleeding-in-hereditary-hemorrhagic

How I treat bleeding in hereditary hemorrhagic telangiectasia The systemic therapies with robust evidence for effectiveness and safety, including bevacizumab, pomalidomide, and antifibrinolytic agents will be the focus, ...