A Phase 1 interventional study of Topical sirolimus ointment in Hereditary Hemorrhagic Telangiectasia (HHT) and Epistaxis, sponsored by Columbia University. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-06.
Sponsored by Columbia University · Phase 1, Interventional, and Treatment
People with hereditary hemorrhagic telangiectasia (HHT) often experience frequent and severe nosebleeds that can disrupt daily life and lead to anemia, medical procedures, and reduced quality of life. This study is testing a new nasal ointment called TOR-582, which contains sirolimus, to determine whether it can be used safely when applied inside the nose. Adults with HHT and frequent nosebleeds will be invited to participate. Participants will first complete one week of observation without treatment, followed by up to 12 weeks of applying the study ointment inside each nostril twice daily. Different participants will receive different strengths of the ointment so researchers can identify the safest dose. During the study, participants will attend study visits, complete questionnaires about their nosebleeds and quality of life, keep a daily nosebleed diary, undergo nasal examinations, and have blood tests to monitor safety and medication levels. The information gained from this study will help determine whether this topical treatment can be safely studied further and will support the development of a new, less invasive option for managing nosebleeds in people with HHT.
This is a Phase I single-center trial evaluating the safety, tolerability, and clinical activity of TOR-582 in adults with HHT-associated epistaxis. The study will include a Phase 1a Dose-Finding study and a preliminary Proof-of-Concept protocol. The study will employ a Bayesian Optimal Interval (BOIN) dose-finding design with accelerated titration. Phase 1a will commence with topical administration of the TOR-582 compound in the nasal cavity, starting with a 1% dose (.2mL, dose level 2) delivered twice daily for a 12-week dosing period.
Participants will complete a 1-week observational baseline period prior to initiation of treatment. The first 4 weeks of treatment will constitute the dose-limiting toxicity (DLT) evaluation period. Participants who complete the DLT evaluation period will continue treatment for an additional 8 weeks, for a total treatment duration of 12 weeks.
The study will enroll up to 27 participants. Patients who fail to complete the dosing regimen for at least 80% of assigned dosages in their assigned cycle of treatment for reasons other than DLT will be excluded from DLT evaluation and may be replaced.
106 studies on the registry are indexed under Telangiectasia, Hereditary Hemorrhagic; 24 are open to participants now.
This study's planned enrollment of 27 is below the median of 33 across 61 interventional studies indexed under Telangiectasia, Hereditary Hemorrhagic.
Browse Telangiectasia, Hereditary Hemorrhagic studies →Columbia University is the lead sponsor of 1,136 studies on the registry; 195 are open to participants now.
Of its 180 completed or terminated interventional studies of FDA-regulated products, 148 (82%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
Adequate bone marrow function defined as:
Exclusion Criteria:
Endoscopic evaluation of nasal cavity (HES-based)
Clinical laboratory evaluation:
Documented hyperproliferative anemia (myelodysplastic syndrome, aplastic anemia, etc.).
a. Current pregnancy or planned pregnancy within the next 6 months, or active breastfeeding.
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.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
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.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
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.
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.
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.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
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.
Drug: Topical sirolimus ointment
Drug: Topical sirolimus ointment
Drug: Topical sirolimus ointment
The active formulation of TOR-582 incorporates sirolimus at concentrations of 5 mg/mL (0.5%), 10 mg/mL (1.0%), and 20 mg/mL (2.0%) along with other active ingredients in an oil-based carrier ointment. Ointment will be applied intranasally twice daily in 0.2mL applications using TC5-R - Topi-CLICK Micro® 5 mL devices, which dispense metered 0.05 mL doses. Dose finding will begin at a dose of 10 mg/mL (1.0%). Doses will escalate sequentially across planned dose levels (Level 1: 5 mg/mL, Level 2: 10 mg/mL, Level 3: 20 mg/mL) as guided by the BOIN-AT design until the Maximum Tolerated Dose is identified.
Also known as: TOR-582
Incidence of dose-limiting toxicities (DLTs)
The occurrence of protocol-defined DLTs during the active treatment at each dose level, used to guide escalation/de-escalation decisions and determine the recommended Phase 1b dose. A DLT is defined as the occurrence of Grade 2 or higher AEs in greater than 25% of participants at a given dose level, or more than one Grade 3 or higher AE at any point in the trial.
Time frame: From enrollment through the first 4 weeks of treatment for each cohort (the DLT evaluation window)
Number of participants with treatment-emergent adverse events (AEs)
The aggregate count of participants experiencing AEs across the entire 12-week treatment period.
Time frame: From enrollment through end of treatment, typically at 12 weeks.
Severity of treatment-emergent adverse events, graded according to the NCI CTCAE v6.0.
The highest severity grade of clinical AEs experienced by each participant. The CTCAE scale ranges from Grade 1 (Mild) to Grade 5 (Death), where higher grades indicate greater clinical severity.
Time frame: From enrollment through the first 4 weeks of treatment for each cohort (the DLT evaluation window)
Whole blood sirolimus trough concentrations
Time frame: Assessed at baseline, after 4 weeks of treatment, and at the end of treatment at 12 weeks
Epistaxis severity, measured by the Epistaxis Severity Score (ESS)
Trends in the ESS at baseline and during and after treatment will quantify changes in bleeding burden. The ESS ranges from 0 to 10, with higher scores indicating greater severity.
Time frame: Assessed at baseline, initiation of treatment, every 4 weeks during treatment, and at the end of treatment, typically at 12 weeks
Patient-reported frequency of epistaxis episodes
Recorded as frequency of entries in the Cure HHT Diary and averaged over 28-day periods to supplement the ESS.
Time frame: Recorded daily from beginning of screening period through end of treatment, typically at 12 weeks.
Patient-reported duration of epistaxis episodes
Recorded via Cure HHT Diary on a six-tiered scale, with a minimum duration of \<1 minute and a maximum of \>60 minutes.
Time frame: Recorded daily from beginning of screening period through end of treatment, typically at 12 weeks.
Patient-reported intensity of epistaxis episodes
Recorded via Cure HHT Diary on a scale ranging from 1 ("spotting") to 6 ("gushing") and averaged over 28-day periods to supplement the ESS. Higher scores indicate greater intensity.
Time frame: Recorded daily from beginning of screening period through end of treatment, typically at 12 weeks.
Patient-reported overall severity of epistaxis episodes
Recorded via Cure HHT Diary on a scale ranging from 1 to 10 and averaged over 28-day periods to supplement the ESS. Higher scores indicate greater overall severity.
Time frame: Recorded daily from beginning of screening period through end of treatment, typically at 12 weeks.
Clinical Global Impression - Severity (CGI-S) score, adapted for epistaxis
The subjective assessment of nosebleed severity, as measured using adapted items from the Clinical Global Impression (CGI) scale. Participants will be asked: "Overall, how would you rate your nosebleeds now?", with response options ranging from 1 ("Excellent - no nosebleeds") to 6 ("Very Poor - nosebleeds are constant or severely disruptive"). Higher scores indicate greater severity.
Time frame: At baseline, initiation of treatment, every 4 weeks during treatment, and at end of treatment (typically at 12 weeks).
Clinical Global Impression - Improvement (CGI-I) score, adapted for epistaxis.
Clinical Global Impression - Improvement (CGI-I) score, adapted for epistaxis. The subjective assessment of treatment-related change in nosebleed severity, as measured using adapted items from the Clinical Global Impression (CGI) scale. Participants will be asked: "Overall, how would you rate your nosebleeds since starting the treatment with this ointment?", with response options ranging from 1 ("much better") to 7 ("much worse"). Higher scores indicate less improvement.
Time frame: Every 4 weeks during treatment, and at end of treatment (typically at 12 weeks)
Clinical Global Impression - Quality of Life (CGI-QoL) score, adapted for epistaxis.
The subjective assessment of the impact of nosebleeds on quality of life, as measured using adapted items from the Clinical Global Impression (CGI) scale. Participants will be asked: "Overall, how would you rate how much your nosebleeds affect your overall quality of life?", with response options ranging from 1 ("not at all") to 6 ("extreme"). Higher scores indicate greater impact on quality of life.
Time frame: At baseline, initiation of treatment, every 4 weeks during treatment, and at end of treatment (typically at 12 weeks)
HHT-Specific Quality of Life (QoL)
Participants will complete a 4-item, validated HHT-specific QoL questionnaire designed to assess the functional impact of HHT-related epistaxis. Each item is scored from 0 (never) to 4 (very often), yielding a total score ranging from 0 (no limitations) to 16 (severe limitations). Higher scores indicate more severe limitations of quality of life.
Time frame: At baseline, initiation of treatment, every 4 weeks during treatment, and at end of treatment (typically at 12 weeks)
Modified QoL-HHT score
The QoL-HHT is a 24-item, disease-specific questionnaire that quantifies multi-faceted impact of HHT on individual patient lives. Each statement is scored on a 5-point Likert scale ranging from 1 = "strongly disagree" to 5 = "strongly agree." Items are categorized into six validated domains: physical limitations (PL), social relationships (SR), concern about bleeding (CAB), relationship with the medical profession (RMP), experience of symptoms (ES), and concern about disease evolution (ED). This trial will use a modified 8-item QoL-HHT score by selecting specified items focused particularly on the overall burden of epistaxis in each participant's daily life, with higher scores indicating greater burden.
Time frame: At baseline, initiation of treatment, every 4 weeks during treatment, and at end of treatment (typically at 12 weeks)
Satisfaction with Social Roles and Activities, measured by PROMIS® Short Form 8a v2.0
This is one of three short-form questionnaires from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS®) which will be used to evaluate the impact of treatment on overall well-being and functioning. Each form yields a standardized T-score generated via the PROMIS® scoring engine, allowing comparison to a normative population (mean = 50, SD = 10). This 8-item measure evaluates satisfaction with social participation and daily responsibilities. Items include statements such as: "I am satisfied with my ability to do regular daily activities." Higher T-scores indicate greater satisfaction with social roles.
Time frame: At baseline, initiation of treatment, every 4 weeks during treatment, and at end of treatment (typically at 12 weeks)
Depression, measured by PROMIS® Short Form 8b v1.0
This is one of three short-form questionnaires from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS®) which will be used to evaluate the impact of treatment on overall well-being and functioning. Each form yields a standardized T-score generated via the PROMIS® scoring engine, allowing comparison to a normative population (mean = 50, SD = 10). This 8-item form assesses depressive symptoms experienced in the past 7 days, including feelings of sadness, hopelessness, and worthlessness. Higher T-scores indicate more severe depressive symptoms.
Time frame: At baseline, initiation of treatment, every 4 weeks during treatment, and at end of treatment (typically at 12 weeks)
Fatigue, measured by PROMIS® Short Form 6a v1.0
This is one of three short-form questionnaires from the NIH Patient-Reported Outcomes Measurement Information System (PROMIS®) which will be usde to evaluate the impact of treatment on overall well-being and functioning. Each form yields a standardized T-score generated via the PROMIS® scoring engine, allowing comparison to a normative population (mean = 50, SD = 10). This 6-item questionnaire measures fatigue severity and its interference with physical and social functioning. Items include: "How fatigued were you on average?" Higher T-scores reflect more severe fatigue.
Time frame: At baseline, initiation of treatment, every 4 weeks during treatment, and at end of treatment (typically at 12 weeks)
EQ-5D Visual Analogue Scale (EQ-VAS)
The EuroQol Visual Analogue Scale is a validated, standardized instrument developed by the EuroQol Group to capture a participant's self-rated health status. Participants indicate their current overall health on a vertical scale ranging from 0 ("worst imaginable health") to 100 ("best imaginable health"), generating a single index value of health-related quality of life. Higher scores indicate greater health-related quality of life.
Time frame: At baseline, initiation of treatment, every 4 weeks during treatment, and at end of treatment (typically at 12 weeks)
Patient Satisfaction with Treatment
Participants will be asked, "Overall, how satisfied are you with the ointment?", with answer choices ranging from 1 ("completely dissatisfied") to 7 ("completely satisfied"). Higher scores indicate greater satisfaction.
Time frame: At end of treatment, typically at 12 weeks
Perceived treatment benefit and satisfaction, measured by Modified TTAQ.
Topical Therapy Adherence Questionnaire (TTAQ) and companion Patient Preference Questionnaire (PPQ) were developed by Zschocke et al. to identify patient- and treatment-related factors that influence adherence to topical therapies. This trial uses a modified 19-item version of the TTAQ, focusing specifically on the Treatment Satisfaction and Benefits to Patient domains and curated to minimize respondent burden and align with the use of topical sirolimus in the nasal mucosa. Participants rate their agreement with each item on a 4-point Likert scale, ranging from 0 ("strongly disagree") to 3 ("strongly agree"), where higher scores indicate greater treatment satisfaction and benefit to patient.
Time frame: At end of treatment (typically at 12 weeks)
Perceived treatment benefit and satisfaction, measured by Modified PPQ
The Topical Therapy Adherence Questionnaire (TTAQ) and companion Patient Preference Questionnaire (PPQ) were developed by Zschocke et al. to identify patient- and treatment-related factors that influence adherence to topical therapies. This trial uses a modified, 6-item version of the PPQ, focusing specifically on the Treatment Satisfaction and Benefits to Patient domains and curated to minimize respondent burden and align with our use of topical sirolimus in the nasal mucosa. Participants rate their agreement with each item on a 4-point Likert scale, ranging from 0 ("strongly disagree") to 3 ("strongly agree"), where higher scores indicate greater treatment satisfaction and benefit to patient.
Time frame: At end of treatment (typically at 12 weeks)
Hematologic Support Score (HSS)
The HSS is a composite measure that combines the assessment of red blood cell transfusion and iron infusion into a single endpoint, enabling evaluation over time. A higher number indicates greater transfusion/infusion burden.
Time frame: During screening and at end of treatment, typically at 12 weeks
Hematologic Impact Score (HIS)
The HIS assesses the total hematologic impact over a reference time frame by accounting for changes in hemoglobin and HSS during that period (a higher number indicates greater improvement in hematologic status).
Time frame: During screening and at end of treatment, typically at 12 weeks
Mean change in hemoglobin concentration from baseline
Measured via standard automated complete blood count (CBC).
Time frame: During screening and at the end of treatment, typically at 12 weeks
Mean change in hematocrit from baseline
Measured via standard automated complete blood count (CBC).
Time frame: During screening and at the end of treatment, typically at 12 weeks
Mean change in mean corpuscular volume (MCV) from baseline
Measured via standard automated complete blood count (CBC).
Time frame: During screening and at the end of treatment, typically at 12 weeks
Mean change in serum ferritin from baseline
Measured via standard iron panel.
Time frame: During screening and at the end of treatment, typically at 12 weeks
Mean change in transferrin saturation from baseline
Measured via standard iron panel.
Time frame: During screening and at the end of treatment, typically at 12 weeks
Number of red blood cell transfusions and parenteral iron administrations during treatment period
Measured via patient reporting.
Time frame: Assessed during screening and at end of treatment, typically at 12 weeks
Endoscopic Disease Activity
Change in nasal telangiectasia severity, assessed by a modified HHT Endoscopy Score (HES). The HES is a clinician-administered scoring system used to assess the severity of nasal telangiectasias during endoscopic evaluation. For this study, five domains will be used: number of sites involved, vascular pattern, crusting, lesion location, and septal perforation. Each is scored from 0 to 3, with higher scores indicating more extensive disease.
Time frame: Assessed during screening, after first 4 weeks of treatment (end of DLT evaluation period), and end of treatment (typically at 12 weeks)
Plan to share: No — Individual participant data (IPD) will not be publicly shared due to the small sample size and potential risk of participant re-identification in this rare disease population.
No publications or documents are linked to this record.
Start is estimated for Mar 2027; primary completion for May 2028, 14 months later.
Since we started tracking on Sep 25, 2026, the dates moved once, on Nov 6, 2026: start Oct 2026 → Mar 2027, primary completion Jul 2027 → May 2028 and completion Dec 2027 → May 2028.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Nov 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Topical Sirolimus
Telangiectasia, Hereditary Hemorrhagic →