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

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot study is to determine the safety and efficacy of oral sirolimus (blood trough level 6-10ng/ml) in patients with HHT that are experiencing moderate or severe epistaxis. The effect of oral sirolimus on epistaxis will be compared to baseline using the Patient-Reported Outcome of cumulative weekly nose Bleeding Duration (PRO-CB). The PRO-CB association with biomarker variability over the duration of the study will be investigated. In the pilot study subjects will be treated with 2mg of sirolimus once daily to obtain a trough level of 6-10ng/ml for 3 months.

Research Team

Marie E Faughnan, MD MSc FRCPC

Principal Investigator

Unity Health Toronto

Eligibility Criteria

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.

Treatment Details

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.

Participant Groups

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+