A Phase 2 interventional study of Tacrolimus capsule (low-dose) in Hereditary Hemorrhagic Telangiectasia and Epistaxis Nosebleed, sponsored by Unity Health Toronto. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-01.
Sponsored by Unity Health Toronto · Phase 2, Interventional, and Treatment
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Among 12 studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada — 1 open to participants now, 3 under way, none of them phase 3. Telangiectasia, Hereditary Hemorrhagic · Canada.
Among the 12 studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada, this one is the 6th largest by enrollment of the 10 interventional ones that give a count, is the only one that started in 2020, is one of 5 in phase 2, and was the 9th registered.
106 studies on the registry are indexed under Telangiectasia, Hereditary Hemorrhagic; 24 are open to participants now.
Browse Telangiectasia, Hereditary Hemorrhagic studies →1 of the 12 studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada is open now. Recruiting first, the newest first:
Diagonal Therapeutics, Inc. · Sites in Canada, Australia, New Zealand
Ages 18+
A study can be open while its sites in Canada have not opened yet or have stopped. Only those recruiting at a site in Canada →
Of the 17 Telangiectasia, Hereditary Hemorrhagic studies recruiting now, 14 (82%) set no upper age limit and 2 (12%) stop at 75 or younger; 6 take children under 18; 3 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
12 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 3 · Phase 2 8
First in 2010; this study’s year is marked. 1 started in 2020.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 10 is below the median of 33 across 61 interventional studies indexed under Telangiectasia, Hereditary Hemorrhagic.
Median enrollment 12 across the 10 interventional studies, 1,284 across the 2 observational. Of the 8 that completed or were terminated, 4 (50%) have results posted.
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3 of 12 have an industry lead sponsor. The 5 most frequent:
Unity Health Toronto is the lead sponsor of 447 studies on the registry; 81 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 1 (20%) have results posted.
Unity Health Toronto has 8 studies filed under Telangiectasia, Hereditary Hemorrhagic — fewer than ten, so there is no comparison to draw.
1 of the studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07623525Diagonal Therapeutics, Inc.DIAG723 in Adults With Hereditary Hemorrhagic Telangiectasia | 2027-11-30 |
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Among the 12 studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada, from their registry updates:
Nothing recorded among them since 2026-09-25.
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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.
The aim is to study is to evaluate low-dose tacrolimus as a treatment for HHT. Rare disease presents a number of challenges in clinical trial design, including recruitment challenges, related power limitations and less knowledge about outcomes measurement. Considering these limitations, as well as the large variability in epistaxis measures across HHT patients, a trial design, with each subject receiving the study drug for six months and for one year an epistaxis daily dairy documentation, providing valuable information about seasonal variation.in epistaxis.
This study will investigate tacrolimus, given its demonstrated anti-angiogenic and anti-inflammatory properties, as well as compelling effects in arteriovenous malformation (AVM) models. Specifically, tacrolimus has been shown to oppose the gene expression upregulation of the identified pro-angiogenic markers, thus resulting in anti-angiogenic effects. There are two mechanisms to this. Firstly, recent evidence has shown tacrolimus to be a potent ALK1 signaling mimetic at the transcriptional level. This is particularly significant given that the ALK1 pathway signaling is lost in HHT via the hallmark ACVRL1 and ENG genes. Independent of its effect on the ALK1 pathway, tacrolimus has been shown to be a potent inhibitor of VGEF signaling.
As mentioned previously, the BMP9-ALK1-endoglin-Smad1/5/9 pathway in HHT, is a novel avenue of interest for treating hemorrhage in HHT and also regressing vascular malformations. Given the upstream inactivation of the ALK1 pathway, therapeutic potential via this pathway is dependent on Smad1/5/8 activation and signaling irrespective of the functional status of the corresponding ALK1 receptors. To this end, tacrolimus has been shown to activate Smad1/5/8 signaling in HHT patient-derived cells, thus confirming its therapeutic potential in HHT.
Tacrolimus also has anti-inflammatory effects, via inhibition of pro-inflammatory cytokines, specifically IL2, which is associated with cytotoxic T cell proliferation and activation. Finally, recent evidence also demonstrated a reduction of vascular pathology in mouse models via tacrolimus administration. Tacrolimus also has the advantages of a proven safety track record for long-term use, given its long history in transplant medicine, and can be orally administered, making it more acceptable to patients. In addition to promising effects in laboratory-based studies, Canadian case study reported the regression of angiodysplasia and reduction of mucosal hemorrhage in a probable HHT patient who underwent liver transplantation following high-output cardiac failure and hepatic AVM development. A recent case report of treatment with oral low-dose -dose tacrolimus in an individual with HHT, found that tacrolimus dramatically improved epistaxis. Based on the evidence to date, the investigators hypothesize that oral low-dose tacrolimus will reduce nasal hemorrhage in HHT subjects, through anti-angiogenic and/or anti-inflammatory mechanisms, both of which have been implicated in HHT.
This clinical trial of oral low-dose tacrolimus (0.025mg/kg/day and adjusted to maintain blood levels of 2-5ng/ml 6-month course) in HHT subjects with moderate-severe recurrent nasal hemorrhage. Drug dosing and safety monitoring will be tailored specifically to the agent studied. The primary outcome will be reduction of bleeding minutes per week. In addition, vascular malformation tissue (cutaneous) will be obtained pre and post-investigational product from some subject, and stained for inflammatory, angiogenic and BMP9-ALK1-endoglin- SMAD1/5/9 pathway markers. In addition, pre-excision, vascular malformations will be imaged with speckle variance optical coherence tomography (SVOCT), in vivo non-invasive micro-angiography, to measure lesion structure, vessel volume and vessel density, as previously described. Tissue and imaging may provide important insights into physiological mechanisms that explain clinical changes. If the drugs studied are effective at reducing nasal hemorrhage, this will have important clinical implications for HHT patients.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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)
low-dose Tacrolimus will be given for 6 months followed by a washout period for 6 months
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.
Time frame: 96 weeks
Change in Epistaxis Severity Score (ESS)
The epistaxis severity score is a six item questionnaire used to calculate a severity of HHT related nose bleeding. Each question is pertaining to the subject's typical symptoms within the last 3 months period. The first three questions are related to frequency, duration and intensity. The forth question whether or not medical attention was sought for nose bleeding. The remaining two questions are related to the presence of anemia and the need for blood transfusion due to nose bleeding. The resulting epistaxis severity score vary between; none 0-1, mild bleeding \>1-4, moderate bleeding \>4-7 and \>7-10 for severe bleeding. The ESS questionnaire will be administered to participants at every clinic visit throughout the 96 weeks of the study.
Time frame: Baseline, Weeks; 12,18,24,30,36,42,48,60,66,72,78,84,96
Change in Chronic Bleeding
Blood samples will be taken to measure change in chronic bleeding as a safety measure. Samples will be taken prior to investigational product for a baseline value. This will be followed by measurements every six weeks during the periods of investigational product for comparative analysis
Time frame: Baseline, Weeks; 12,18,24,30,36,42,48,60,66,72,78,84,96
Micro-Imaging to measure regression of Vascular Malformations
Telangiectases will be micro-imaged using an established medical imaging technique speckle variance optical coherence tomography (SVOCT). The micro-imaging will be used for vasculature measurements and structural images of the telangiectases.
Time frame: week 12, week 36, week 60, week 84
The use of Telangiectasia tissue sample to look at the mechanisms of action of Tacrolimus
A punch biopsy of one cutaneous telangiectasia will be performed at two time points during the study. The biopsy tissue sample will be taken at the end of each 6 month active comparator treatment. The tissue will be analyze and stained for inflammatory, angiogenesis and BMP9-ALK1-endoglin-Smad1/5/9 pathway markers (VEGF, MMP-9, COX-2, Endoglin, ALK1 ) before and after treatment with Tacrolimus
Time frame: week 36, week 84
Change in Biomarkers
In order to understand the mechanisms of Tacrolimus effects on vascular malformations and hemorrhage in HHT a serum/plasma sample will be collected before and after treatment with Tacrolimus to measure inflammatory, angiogenesis and BMP9-ALK1-endoglin-Smad1/5/9 pathway markers (VEGF, MMP-9, Thrombospondin-2, ESR, CRP, endothelin)
Time frame: Weeks: 12, 24, 36, 48, 60, 72, 84, 96
Plan to share: No
No publications or documents are linked to this record.
Ran from Oct 2020 to primary completion in Jan 2024, 38 months.
Of 14 phase 2 interventional studies under Telangiectasia, Hereditary Hemorrhagic, half reached primary completion within 36 months of starting (the median), counting those still running; a quarter within 29 and three quarters within 55. This study's 38 months is close to that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Tacrolimus
Telangiectasia, Hereditary Hemorrhagic →