Sirolimus for Nosebleeds in HHT

NCT05269849 | Completed Phase 2 Results DMC

• 1 other identifier: 200421448
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nosebleeds; Epistaxis; Hereditary Hemorrhagic Telangiectasia

Keywords

Hereditary Hemorrhagic Telangiectasia; HHT; Sirolimus

Outcome Measures

Primary Outcomes (10)

• Electrolytes

  Number of participants with clinically significant abnormal electrolytes. Electrolytes include, Sodium, potassium, chloride, total CO2

  9 months

• Hemoglobin

  Number of participants with clinically significant abnormal Hemoglobin

  9 months

• Renal Function

  Number of participants with clinically significant abnormal urea and creatinine

  9 months

• Liver Function

  Number of participants with clinically significant abnormal AST, ALT, and total bilirubin.

  9 months

• Change in Ferritin Levels

  Number of participants with clinically significant abnormal ferritin levels

  9 months

• Blood Glucose Level

  Number of participants with clinically significant abnormal glucose

  9 months

• Lipid Assessment

  Number of participants with clinically significant abnormal total cholesterol and triglycerides

  9 months

• Total Number of Adverse Events (AEs)

  Adverse events were monitored throughout the entire 9-month study period, including the 3-month baseline, 3-month treatment, and 3-month follow-up phases. However, only adverse events that occurred during the 3-month treatment period (i.e., when participants were actively receiving study drug) are reported here. This outcome measure is reporting the total number of adverse events across all participants that occurred during the 3-month treatment period. Adverse events were collected through patient self-reporting, clinical assessments at scheduled visits, and laboratory safety monitoring.

  3 months

• Total White Blood Cells

  Number of participants with clinically significant abnormal total WBC

  9 months

• Red Blood Cells and Platelets

  Number of participants with Clinically Significant RBCs and platelets

  9 months

Secondary Outcomes (3)

• Change in Epistaxis Duration (PRO-CB)

  9 months

• Exploratory Biomarker Analysis Related to Angiogenesis and Inflammation

  9 months

• Change in Epistaxis Severity Score (ESS) at Treatment and Follow-up Periods Compared to Baseline

  9 months

Study Arms (1)

All Participants

EXPERIMENTAL

All participants received Sirolimus and were followed over the 9-month study period (3-month baseline, 3-month treatment period, 3-month follow up period). During 3-month treatment period, oral sirolimus was provided with a target blood trough of 6-10 ng/ml

Drug: Sirolimus

Interventions

Sirolimus DRUG

Oral sirolimus provided with starting dose of 2mg once daily, adjusted to maintain drug blood levels of 6-10 ng/ml (3-month course)

All Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Clinical HHT diagnosis (8) or genetic diagnosis of HHT
• Epistaxis at least 15 min per week.
• COVID-19 Vaccine (2 doses)
• Ability to give written informed consent, including compliance with the requirements of the study.

You may not qualify if:

• Allergy/intolerance to the study drug or related agents
• Unstable medical illness
• Acute infection
• Creatinine \> ULN (upper limit of normal)
• Liver transaminases (AST or ALT) \>= 2x ULN
• Women participant who are pregnant or breastfeeding or plan to become pregnant during the duration of the study
• Women of childbearing potential not on effective contraception.
• Male participants of reproductive potential whose female partners are of childbearing potential and are not planning to use highly effective contraceptive method
• Immunocompromised
• History of malignancy
• Known untreated dyslipidemia (20% above the ULN of total cholesterol and triglycerides)
• Specific contra-indications for study drug (detailed in the product monograph)

Sponsors & Collaborators

• Unity Health Toronto: lead
• National Institutes of Health (NIH): collaborator
• University of California, San Francisco: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (6)

• Faughnan ME, Mager JJ, Hetts SW, Palda VA, Lang-Robertson K, Buscarini E, Deslandres E, Kasthuri RS, Lausman A, Poetker D, Ratjen F, Chesnutt MS, Clancy M, Whitehead KJ, Al-Samkari H, Chakinala M, Conrad M, Cortes D, Crocione C, Darling J, de Gussem E, Derksen C, Dupuis-Girod S, Foy P, Geisthoff U, Gossage JR, Hammill A, Heimdal K, Henderson K, Iyer VN, Kjeldsen AD, Komiyama M, Korenblatt K, McDonald J, McMahon J, McWilliams J, Meek ME, Mei-Zahav M, Olitsky S, Palmer S, Pantalone R, Piccirillo JF, Plahn B, Porteous MEM, Post MC, Radovanovic I, Rochon PJ, Rodriguez-Lopez J, Sabba C, Serra M, Shovlin C, Sprecher D, White AJ, Winship I, Zarrabeitia R. Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Ann Intern Med. 2020 Dec 15;173(12):989-1001. doi: 10.7326/M20-1443. Epub 2020 Sep 8.

  PMID: 32894695 BACKGROUND

• Merlo CA, Yin LX, Hoag JB, Mitchell SE, Reh DD. The effects of epistaxis on health-related quality of life in patients with hereditary hemorrhagic telangiectasia. Int Forum Allergy Rhinol. 2014 Nov;4(11):921-5. doi: 10.1002/alr.21374. Epub 2014 Aug 21.

  PMID: 25145809 BACKGROUND

• Whitehead KJ, Sautter NB, McWilliams JP, Chakinala MM, Merlo CA, Johnson MH, James M, Everett EM, Clancy MS, Faughnan ME, Oh SP, Olitsky SE, Pyeritz RE, Gossage JR. Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia: A Randomized Clinical Trial. JAMA. 2016 Sep 6;316(9):943-51. doi: 10.1001/jama.2016.11724.

  PMID: 27599329 BACKGROUND

• Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000 Mar 6;91(1):66-7. doi: 10.1002/(sici)1096-8628(20000306)91:13.0.co;2-p.

  PMID: 10751092 BACKGROUND

• Sadick H, Naim R, Sadick M, Hormann K, Riedel F. Plasma level and tissue expression of angiogenic factors in patients with hereditary hemorrhagic telangiectasia. Int J Mol Med. 2005 Apr;15(4):591-6.

  PMID: 15754019 BACKGROUND

• Wetzel-Strong SE, Weinsheimer S, Nelson J, Pawlikowska L, Clark D, Starr MD, Liu Y, Kim H, Faughnan ME, Nixon AB, Marchuk DA. Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations. Orphanet J Rare Dis. 2021 Sep 3;16(1):372. doi: 10.1186/s13023-021-02009-7.

  PMID: 34479577 BACKGROUND

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Epistaxis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Marie Faughnan
• Organization: Unity Health Toronto

marie.faughnan@unityhealth.to

416-864-5412

Study Officials

• Marie E Faughnan, MD MSc FRCPC

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Model Details: Open label

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: March 8, 2022
• Study Start: March 16, 2022
• Primary Completion: December 2, 2024
• Study Completion: December 2, 2024
• Last Updated: June 4, 2026
• Results First Posted: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)