ClinicalTrials.gg
Not yet recruitingNCT03850730Updated Sep 8, 2022

Pazopanib for the Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia

A Phase 1/2 interventional study of Pazopanib in Hereditary Hemorrhagic Telangiectasia and Epistaxis, sponsored by Cure HHT. Not yet recruiting. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2022-09-08.

Sponsored by Cure HHT · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Primary completion was expected by Jun 2025, 1 year 4 months ago, but the record still lists the study as not yet recruiting.
Phase
Phase 1/2
Study type
Interventional
Enrollment
30
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study summary

Investigators will test the value of very low dose Pazopanib administered to patients with hereditary hemorrhagic telangiectasia for the reduction in the severity of nose bleeds in those with frequent and long duration bleeding episodes.

Read the detailed description

Based on frequency and nose bleed duration, a non-randomized, single arm, open label study of 30 hereditary hemorrhagic telangiectasia patients will be treated with very low dose Pazopanib [25mg-similar] for between 16 and 24 weeks.. The primary endpoint is a reduction in bleeding duration of 50% or more, along with multiple secondary related endpoints, including bleed frequency, blood counts and quality of life; as compared to 6-12 weeks of baseline characteristics. If after the first 8 weeks of therapy benefit is suboptimal, dose advance to 50mg-similar daily can be considered.

02

Conditions studied

  • Hereditary Hemorrhagic Telangiectasia
  • Epistaxis

Keywords

  • osler-weber-rendu
  • nose bleeds
  • open label
  • HHT
  • Pazopanib
03

In context

Telangiectasia, Hereditary Hemorrhagic

106 studies on the registry are indexed under Telangiectasia, Hereditary Hemorrhagic; 24 are open to participants now.

This study's planned enrollment of 30 is close to the median of 33 across 61 interventional studies indexed under Telangiectasia, Hereditary Hemorrhagic.

Browse Telangiectasia, Hereditary Hemorrhagic studies →

Lead sponsor

Cure HHT is the lead sponsor of 3 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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.

Inclusion criteria

  • a definite diagnosis of hereditary hemorrhagic telangiectasia defined as having at least 3 of the following criteria:

    • Spontaneous and recurrent epistaxis.
    • Multiple telangiectasias at characteristic sites: lips, oral cavity, fingers, nose.
    • Visceral lesions: GI telangiectasia, pulmonary, hepatic, cerebral or spinal AVMs.
    • A first degree relative with hereditary hemorrhagic telangiectasia according to these criteria.
    • OR a gene sequencing diagnosis of hereditary hemorrhagic telangiectasia

      1. Epistaxis due to hereditary hemorrhagic telangiectasia at least 2x per week, for a cumulative duration of at least 25 minutes per week
      1. Epistaxis is clinically stable during the 12 weeks prior to screening in the clinical judgment of the investigator (i.e. no major changes in frequency or duration of epistaxis).
      1. Participant agrees not to undergo cautery of nasal telangiectasias or take any experimental therapies for hereditary hemorrhagic telangiectasia other than the study drug while participating in the study.
      1. Male or female [non-child bearing potential]

Exclusion criteria

Exclusion Criteria:

  1. Participant has known immediate or delayed reaction or idiosyncrasy to drugs chemically related to pazopanib that in the opinion of the investigator contradicts their participation.
  2. Currently has untreated cerebral arterio-venous malformations (AVMs), cerebral arteriovenous fistulae, or cerebral cavernous malformations (CCMs) (Note: MRI scan does not need to be repeated at screening if AVMs, arterio-venous fistulas and CCMs were absent on a scan at age ≥18 years).
  3. Currently has perfused pulmonary AVMs with feeding artery diameter >3mm.
  4. Known significant bleeding sources other than nasal or gastrointestinal.
  5. Systemic use of a vascular endothelial growth factor inhibitor in the past 3 months or previous enrollment in this study.
  6. Active and recent onset of diarrhea.
  7. Current or recent (in the last 5 years) (except non-melanoma skin cancers)
  8. Participant has had major surgery (e.g. surgical ligation of an AVM) or trauma within 28 days or had minor surgical procedures (e.g. central venous access line removal) within 7 days prior to dosing, the latter representing a recent wound, fracture or ulcer
  9. Participant has a planned surgery during the period to include active treatment and 6 weeks of follow up.
  10. Participant has clinically significant gastrointestinal abnormalities (other than hereditary hemorrhagic telangiectasia related vascular lesions)
  11. Participant during the 6 months prior to first dose of study drug has a history of cerebrovascular accident (including ), pulmonary embolism, untreated deep vein thrombosis (DVT), myocardial infarction, or any other thrombotic event.
  12. ≥450 msec, based on averaged QTc values of triplicate ECGs obtained over a brief recording period [The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual overread. The same QT correction formula must be used for each individual participant to determine eligibility for and withdrawal from the study.]
  13. \<6 g/dL.
  14. \< 100x109/L.
  15. (INR) >1.2x and activated partial thromboplastin time (aPTT)>1.2x upper limit of normal.
  16. >2x upper limit of normal.
  17. >1.5x upper limit of normal (isolated bilirubin >1.5x upper limit of normal is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
  18. Participant has poorly controlled hypertension [defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg. Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry [between screen and baseline]. At Screening, blood pressure must be assessed three times and the mean SBP/DBP must be \<140/90 mmHg in order for a participant to be eligible for the study.]
  19. Substantive renal disease ( \<30 mL/min/1.73m2calculated using the formula)
  20. Echo derived \<30%.
  21. Thyroid stimulating hormone > upper limit of normal.
  22. Urine protein to creatinine ratio >0.3.
  23. \<1500/mm3.
Terms in these criteria, in plain language(15)

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.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

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.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

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.

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).

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.

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.

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.

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.

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.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (estimated)

Study arms

  • Experimental
    Pazopanib

    Pazopanib, initiated after a baseline period at 25mg oral dosing daily, for this one treatment arm, to be compared to the patient's baseline. If endpoint not achieved and safety demonstrated in 2-3mths, an advance of dose to 50mg daily for the ensuing 3mths of study will be considered.

    Drug: Pazopanib

Interventions

  • Active pharmaceutical ingredient plus excipients filled into a capsule for the lower dosing necessary in this study

    Also known as: Pazopanib capsule

06

What researchers measure

Primary outcomes

  1. Percent change in epistaxis duration in minutes

    A daily electronic record of each bleed, with start and end time, provides the daily epistaxis duration, compounded over each 3 weeks of study time

    Time frame: Summed minutes of bleeding at baseline 3 weeks and the last 3 weeks of dosing, over16-24 weeks of dosing

Secondary outcomes

  1. Percent change in average gushing frequency

    Patient rated intensity of each bleed, as in 0 or 1, averaged over 3 wk periods.

    Time frame: Last 3 weeks of drug period vs baseline 3 weeks; over 16-24 weeks of dosing

  2. Percent change in average bleed frequency

    Annotated number of bleeds per day, and summed over 3 week periods

    Time frame: Last 3 weeks compared to the baseline 3 weeks; over 16-24 weeks of dosing

  3. Absolute [gm/dl] change in serum hemoglobin

    Serum values drawn every 3 weeks

    Time frame: comparing last 6 weeks to baseline 3-6 weeks; over 16-24 weeks of drug dosing

  4. Change in the frequency of blood transfusions

    Use of packed red blood cells over 6 week time periods.

    Time frame: Final 6 weeks of study, compared to baseline 3-6 weeks; over 16- 24 weeks of dosing

  5. Change in the frequency of IV iron infusions

    Number of interval IV iron infusions in 6 week periods

    Time frame: Last 6 weeks of dosing to first 6 weeks; over 16-24 weeks of drug administration

  6. Percent change in the per bleed average epistaxis severity

    Epistaxis severity score \[0-10\] housed in the current patient reported outcome instrument will be averaged

    Time frame: The final 3 weeks to the baseline 3 weeks of the study; for a16-24 week duration study

  7. Daily monitoring for change in systolic blood pressure [mm mercury] using daily recordings

    Patients rising above 140 mm mercury, or those who increase by 20 or more mm mercury will trigger protocol defined treatments.

    Time frame: Daily from baseline through up to 24 weeks till on-drug study completion.

  8. Daily monitoring for change in diastolic blood pressure [mm mercury]

    Patients rising above 90 mm mercury, or those who increase by 10 mm mercury or more will trigger protocol defined treatments.

    Time frame: Daily from baseline through up to 24 weeks till on-drug study completion

  9. Number of participants with changes in alanine aminotransferase [liver function test]

    measurement every 3 weeks to evaluate fold increase with use of drug

    Time frame: Baseline and throughout the 16-24 week dosing period

  10. Monitor for active and safe trough serum drug concentrations

    Assays to be analyzed to evaluate the exposures done to remain within safe and effective range \[1ug/ ml to 10ug/ml\].....

    Time frame: Over 16-24 week duration of study; once at steady state for each administered dose

  11. Evaluate for change in composite mental quality of life scores

    short form health survey 36 \[range 1-100, higher number representing better self-reported mental health\]

    Time frame: baseline, week 12 and at study drug-dosing end; 16, 20 or 24weeks

  12. Evaluate for change in composite physical quality of life scores

    short form health survey 36 \[range 1-100, higher number representing better self-reported physical health\]

    Time frame: baseline, week 12 and at study drug-dosing end; up to 24 weeks.

  13. Evaluate for change in fatigue composite scores

    Patient-report outcome measurement information system-fatigue; \[0-100 scale; lower number representing less fatigue\]. Queries the degree of fatigue and the implications on physical functioning. Reduction of 5 or more in the composite score represents clinically relevant reductions in fatigue.

    Time frame: baseline and study end; up to 24 weeks

Other outcomes

  1. Interrogate levels of Iron stores

    Ferritin serum levels \[normal range 12 ug/ ml to 150ug/ml female, 300ug/ ml male\]. However, above 30ug/ ml valued as relevant for proper erythropoiesis\]

    Time frame: baseline and at on-drug study end; 16, 20 or 24 weeks depending on study duration

  2. Characterize change in left ventricular stress

    NTproBNP serum values represent a surrogate for left ventricular stress \[\<125pg/ml normal, while above 350pg/ml high and potentially consistent with heart failure\]

    Time frame: baseline and on-drug study end; 16, 20 or 24 weeks depending on study duration]

07

Study locations

No study locations are listed for this record.

08

References and documents

Individual participant data

Plan to share: Undecided — After the PI and associates produce the primary and adjunct reports, these data can be posted on data files for public access

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Start is estimated for Jul 2023; primary completion for Jun 2025, 23 months later.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 12, 2019
First posted
Feb 22, 2019
StartEst.
Jul 1, 2023
Primary completionEst.
Jun 30, 2025
CompletionEst.
Dec 31, 2025
Last update
Sep 8, 2022
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 8, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03850730
Lead sponsor
Cure HHT
Collaborators
University of North Carolina
Responsible party
Sponsor
First posted
Feb 22, 2019
Start date
Jul 1, 2023 (estimated)
Primary completion
Jun 30, 2025 (estimated)
Completion
Dec 31, 2025 (estimated)
Last update
Sep 8, 2022

Study contacts

Nicole Schaefer
Contact
nicole.schaefer@curehht.org
410-357-9932
Dennis L Sprecher, MD
Contact
dennis.sprecher@curehht.org
410-357-9932
Raj Kasthuri, MD
principal investigator · University of North Carolina

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.

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Discussion

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Studies of the drug tested here: Pazopanib

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