Trial Outcomes & Findings for Sirolimus for Nosebleeds in HHT (NCT NCT05269849)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

9 months

Results posted on

2026-06-04

Participant Flow

Participant milestones

Participant milestones
Measure	Overall Study Period The 9-month trial was broken down into 3-month baseline period, 3 months on sirolimus, and 3 months follow up phase.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sirolimus for Nosebleeds in HHT

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Final Analysis Population n=10 Participants Includes only the 10 participants who completed all study visits and were included in the final analysis.
Age, Continuous	57 years STANDARD_DEVIATION 9.7 • n=9 Participants
Sex: Female, Male Female	5 Participants n=9 Participants
Sex: Female, Male Male	5 Participants n=9 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=9 Participants
Race (NIH/OMB) Asian	0 Participants n=9 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=9 Participants
Race (NIH/OMB) Black or African American	1 Participants n=9 Participants
Race (NIH/OMB) White	9 Participants n=9 Participants
Race (NIH/OMB) More than one race	0 Participants n=9 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=9 Participants

PRIMARY outcome

Timeframe: 9 months

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

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Electrolytes	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 9 months

Number of participants with clinically significant abnormal Hemoglobin

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Hemoglobin	2 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 9 months

Number of participants with clinically significant abnormal urea and creatinine

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Renal Function	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 9 months

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

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Liver Function	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 9 months

Number of participants with clinically significant abnormal ferritin levels

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Change in Ferritin Levels	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 9 months

Number of participants with clinically significant abnormal glucose

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Blood Glucose Level	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 9 months

Number of participants with clinically significant abnormal total cholesterol and triglycerides

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Lipid Assessment	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 3 months

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.

Outcome measures

Outcome measures
Measure	Treatment Period Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Total Number of Adverse Events (AEs)	—	—	20 Adverse Events

PRIMARY outcome

Timeframe: 9 months

Number of participants with clinically significant abnormal total WBC

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Total White Blood Cells	2 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 9 months

Number of participants with Clinically Significant RBCs and platelets

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Red Blood Cells and Platelets	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 9 months

Epistaxis was assessed using the Patient-Reported Outcome of Cumulative Weekly Nose Bleeding Duration (PRO-CB), collected via daily patient diary throughout the study (3-month baseline, 3-month treatment, and 3-month follow-up periods).

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Change in Epistaxis Duration (PRO-CB)	144 minutes Interval 28.0 to 359.0	53 minutes Interval 11.0 to 230.0	126 minutes Interval 28.0 to 339.0

SECONDARY outcome

Timeframe: 9 months

Plasma samples were collected for future analysis of circulating biomarkers associated with angiogenesis and inflammation in HHT. The specific biomarker panel is to be finalized in collaboration with the HHT Study Team, and may include proteins such as ANG2, sICAM1, PIGF, TSP2, sVEGFR2, BMP9, IL-6, SDF1, sVCAM1, sVEGFR3, sCD73, sIL6R, TGF-β1, VEGF, sENG, OPN, TGF-β2, VEGF-C, GP130, PDGF-AA, sTGFβR3, VEGF-D, HGF, PDGF-BB, TIMP1, and sVEGFR1. Quantification methods (e.g., ELISA, multiplex immunoassay) and timepoints will be determined prior to analysiThis is an exploratory, post-treatment outcome measure and no data are yet available.s. This is an exploratory, post-treatment outcome measure and no data are yet available.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 9 months

Epistaxis severity was measured using the Epistaxis Severity Score (ESS). ESS was administered at each clinic visit throughout the 9-month study period. However, only the ESS scores collected at Week 12 (end of baseline), Week 24 (end of treatment), and Week 36 (end of follow-up) were used for this outcome analysis. The ESS ranges from 0 to 10, with higher scores indicating more severe epistaxis.

Outcome measures

Outcome measures
Measure	Treatment Period n=10 Participants Three months of treatment period. Patients were provided sirolimus (starting dose of 2 mg) once daily, orally adjusted as need to maintain drug blood levels of 6-10 ng/ ml	Follow-up n=10 Participants Three month follow up period where patients are off the study drug	Baseline n=10 Participants Three months baseline period where participants were not on sirolimus
Change in Epistaxis Severity Score (ESS) at Treatment and Follow-up Periods Compared to Baseline	4.42 units on a scale Interval 2.93 to 5.98	3.33 units on a scale Interval 2.25 to 5.07	4.78 units on a scale Interval 3.71 to 6.45

Adverse Events

Oral Sirolimus Tablets

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Oral Sirolimus Tablets n=10 participants at risk 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: Sirolimus tablets given for 3 months followed by a washout period of 3 months
Nervous system disorders Headaches	40.0% 4/10 • 9 months
Infections and infestations Upper Respiratory Tract Infection	40.0% 4/10 • 9 months
Skin and subcutaneous tissue disorders Skin reaction/rash	40.0% 4/10 • 9 months
Respiratory, thoracic and mediastinal disorders Epistaxis (worsened)	30.0% 3/10 • 9 months
Gastrointestinal disorders Diarrhea	30.0% 3/10 • 9 months
Blood and lymphatic system disorders Anemia (worsened)	20.0% 2/10 • 9 months
Blood and lymphatic system disorders Low WBC count	20.0% 2/10 • 9 months
Psychiatric disorders Insomnia	20.0% 2/10 • 9 months
Gastrointestinal disorders Dry mouth	20.0% 2/10 • 9 months
Gastrointestinal disorders Nausea	20.0% 2/10 • 9 months
Gastrointestinal disorders vomitting	20.0% 2/10 • 9 months
Gastrointestinal disorders Oral mucosal lesion	20.0% 2/10 • 9 months
Respiratory, thoracic and mediastinal disorders Asthma exacerbation	10.0% 1/10 • 9 months
General disorders Fatigue	10.0% 1/10 • 9 months
Nervous system disorders Restless leg	10.0% 1/10 • 9 months
Metabolism and nutrition disorders Low appetite and weight loss	10.0% 1/10 • 9 months
Infections and infestations Urinary tract infection	10.0% 1/10 • 9 months
Renal and urinary disorders Urination worsened	10.0% 1/10 • 9 months
Gastrointestinal disorders Oral bleeding (worsened)	10.0% 1/10 • 9 months
Metabolism and nutrition disorders Hypoglycemia	10.0% 1/10 • 9 months

Additional Information

Dr. Marie Faughnan

Unity Health Toronto

Phone: 416-864-5412

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place