Tacrolimus Trial for Hereditary Hemorrhagic Telangiectasia (HHT)

NCT04646356 | Completed Phase 2 DMC

• 1 other identifier: 170518448
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the effectiveness of oral low-dose tacrolimus for the treatment of recurrent nasal hemorrhage in HHT subjects. The primary outcome for the trials will be the reduction of epistaxis severity (minutes of bleeding per week). The biological outcomes of interest are the regression of vascular malformations as well as tissue and circulation biomarkers of the relevant mechanistic pathways. In this Phase II open label trial, we estimate a sample size of 30 subjects with HHT, with moderate-severe recurrent epistaxis will be required. Subject will be treated with a 6-month course of tacrolimus twice daily.

Conditions

Hereditary Hemorrhagic Telangiectasia; Epistaxis Nosebleed

Keywords

Hereditary Hemorrhagic Telangiectasia; HHT; Tacrolimus

Outcome Measures

Primary Outcomes (1)

• The change in epistaxis (nose bleeding) severity using low-dose Tacrolimus

  Participants will be asked to maintain a daily diary for the duration of the study (96 weeks). Participants will record all epistaxis events daily, noting the duration in minutes and whether or not there was gushing during each nosebleed. The change in epistaxis severity will be measured from a sum of duration of all bleeding events each week, as measured from the participant daily diary.

  96 weeks

Secondary Outcomes (5)

• Change in Epistaxis Severity Score (ESS)

  Baseline, Weeks; 12,18,24,30,36,42,48,60,66,72,78,84,96

• Change in Chronic Bleeding

  Baseline, Weeks; 12,18,24,30,36,42,48,60,66,72,78,84,96

• Micro-Imaging to measure regression of Vascular Malformations

  week 12, week 36, week 60, week 84

• The use of Telangiectasia tissue sample to look at the mechanisms of action of Tacrolimus

  week 36, week 84

• Change in Biomarkers

  Weeks: 12, 24, 36, 48, 60, 72, 84, 96

Study Arms (1)

Tacrolimus immediate-release capsules

EXPERIMENTAL

subjects will be treated with a 6 months course of oral low-dose tacrolimus capsules to be taken twice daily starting dose of 0.025 mg/kg/day, adjusted to maintain drug blood levels of 2-5ng/ml

Drug: Tacrolimus capsule (low-dose)

Interventions

Tacrolimus capsule (low-dose) DRUG

low-dose Tacrolimus will be given for 6 months followed by a washout period for 6 months

Tacrolimus immediate-release capsules

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 or personal genetic diagnosis of HHT
• Epistaxis at least 15 min per week (mean for past month)
• At least one telangiectasia (skin or mucosal) available for micro-imaging.
• 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
• BHCG level \<6 IUL (re-test if 6-24 IU/L)
• Specific contra-indications for study drug (detailed in the product monograph)
• Abnormal ECG where the QTc \>480msec

Sponsors & Collaborators

• Unity Health Toronto: lead
• United States Department of Defense: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B1W8, Canada

Location

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic

Interventions

Tacrolimus

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Marie E Faughnan, MD,MSc,FRCPC

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open Label

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: November 27, 2020
• Study Start: October 20, 2020
• Primary Completion: January 15, 2024
• Study Completion: October 21, 2024
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)