AzTrials
AzTrials

Hereditary Hemorrhagic TelangiectasiaPhase 2/3PazNCT03850964

Effects of Pazopanib on Hereditary Hemorrhagic Telangiectasia Related Epistaxis and Anemia (Paz)

A Phase 2/3 study testing Pazopanib in people with Hereditary Hemorrhagic Telangiectasia and Epistaxis, run by Cure HHT at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

During the Efficacy Study (Part B), the investigators will study whether Pazopanib, taken daily for 24 weeks, will reduce the severity of nose bleeds in patients with hereditary hemorrhagic telangiectasia (HHT). Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Pazopanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
71 participants
Where
11 sitesUnited States
Study dates
8 May 2023to 26 Aug 2026
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A definite or probable diagnosis of hereditary hemorrhagic telangiectasia (HHT):
  • Definite clinical HHT 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 HHT according to these criteria.
Show all 24Show fewer
  • OR a definite diagnosis of HHT based on a pathogenic genetic mutation for HHT.
  • OR probable HHT based on having 2 of the above criteria with high clinical suspicion of HHT.
  • Stable IV iron use and/or blood transfusions stable for 12 weeks prior to test product initiation.
  • Must agree not to undergo cautery of nasal telangiectasias or to start new therapies for HHT while on study.
  • Women of childbearing potential must agree to abstinence or to use an acceptable double method contraception until 4 weeks after drug termination. Pregnancy testing will be done throughout the trial.
  • Men are mandated to use condoms.
  • Capable of giving signed informed consent.
  • Able and willing to return for outpatient visits at the protocol specified intervals.
  • Able and willing to complete blood pressure monitoring at home.
  • Able and willing to complete daily patient reported outcome measurements at home.
  • Must meet all of the inclusion criteria for either:
  • Severe Anemia Cohort:
  • Anemia mainly due to HHT (in the judgment of the PI) with average Hgb <10 g/dL regardless of gender (average of at least three measures during screening and run in).
  • Epistaxis averaging at least 5 min/week over the six-week baseline and is generally stable in the clinical judgement of the investigator.
  • Severe Epistaxis Cohort:
  • Anemia mainly due to HHT (in the judgment of the PI) with Hgb <12 g/dL in women or <13 g/dL in men (average of at least three measures during screening and run in).
  • Epistaxis averaging at least 20 min/week over the six-week baseline and is generally stable in the clinical judgement of the investigator.
  • Part B

Who cannot join

  • Participant has known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib that in the opinion of the investigator contradicts their participation.
  • Currently has incompletely treated cerebral arterio-venous malformations (AVMs) or cerebral arteriovenous fistulas (AVFs) that are symptomatic or have high-risk features detected on either MRI/MRA or digital subtraction angiography. High-risk features include: microhemorrhage seen on MRI; feeding artery aneurysm, nidus aneurysm or venous outflow stenosis seen on MRA, CTA, or catheter angiography. Non-shunting vascular brain lesions such as capillary vascular malformations, telangiectasias, and cavernous malformations are not an exclusion criterion. (Note: MRI scan does not need to be repeated at screening if AVMs and AVFs were absent on a scan at age ≥18 years).
  • Currently has perfused pulmonary AVMs with feeding artery diameter ≥ 3mm.
  • Known significant bleeding sources other than nasal or gastrointestinal.
  • Systemic use of a potent VEGF inhibitor (e.g., direct inhibitors of VEGF-receptor signaling such as sunitinib) in the 4 weeks prior to enrollment. Systemic use of bevacizumab in the 6 weeks prior to enrollment due to its longer half-life.
  • Active and recent onset of clinically significant diarrhea.
Show all 32Show fewer
  • Current or recent (in the last 5 years) malignancies (except non-melanoma skin cancers)
  • 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
  • Participant has a planned surgery during periods of active treatment and 6 weeks of follow up; case by case evaluation if PI desires inclusion with medical monitor agreement.
  • Participant has clinically significant gastrointestinal abnormalities (other than hereditary hemorrhagic telangiectasia related vascular lesions).
  • Participant during the 6 months prior to first dose of study drug has a history of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism, untreated deep vein thrombosis (DVT), myocardial infarction, or any other thrombotic event.
  • Presence of intrinsic heart disease as evidenced by any of the following: Echo derived left ventricular ejection fraction < 45%; Unstable obstructive CAD; history of MI, CABG, or PCI in the last 6 months; Infiltrative and/or restrictive cardiomyopathies; Significant pericardial disease; or clinical heart failure with more than moderate mitral valve or aortic valve disease. In the absence of clinical heart failure, EKG abnormalities, or known cardiac functional disease (e.g., MI or cardiomyopathy), a previous echo during adulthood is adequate. If there is history for coronary disease or cardiomyopathy, an echo in the past 5 years will be adequate for screening. If the patient has current clinical heart failure, a recent cardiac event in last 5 yrs, or a cardiac event since the most recent echo, an echo in the past 6 months will be necessary for screening. Clinical heart failure due to liver AVM or anemia, and not associated with the above findings (with an EF >=45%) will be eligible for enrollment.
  • Unable or unwilling to discontinue use of prohibited medications list in Section 6.5.2 for at least 14 days or 5 half-lives of a drug (whichever is longer) prior to the randomization and for the duration of the study.
  • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the start of randomization: 4 weeks, 4 half-lives or the duration of the biological effect of the investigational product (whichever is longer).
  • QT corrected interval >450 msec for men or >460 msec for women, based on averaged QT corrected interval values of triplicate ECGs obtained over a brief recording period.
  • History of familial prolonged QT.
  • Any concomitant medication which is known to prolong QT.
  • Average baseline hemoglobin <6 g/dL.
  • Platelets < 75x10^9 /L.
  • International normalized ratio (INR) > 1.5x ULN or activated partial thromboplastin time (aPTT) > 1.5x ULN (unless due to known concurrent medications, e.g. warfarin).
  • Alanine Transaminase (ALT) >2 x upper limit of normal.
  • Bilirubin >1.5x upper limit of normal (isolated bilirubin >1.5x upper limit of normal is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
  • Participant has poorly controlled hypertension [defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg]. If BP is poorly controlled at screen visit, initiation or adjustment of antihypertensive medication(s) is permitted during the run-in period prior to randomization. Prior to randomization, blood pressure must be assessed three times and the mean SBP/DBP must be < 140/90 mmHg in order for a patient to be randomized.
  • Substantive renal disease (eGFR <30 mL/min/1.73m2calculated using the Cockcroft-Gault formula)
  • Echo derived left ventricular ejection fraction < 45%.
  • Thyroid stimulating hormone (TSH) > 1.5 x upper limit of normal.
  • Urine protein to creatinine ratio > 0.4.
  • Neutrophil count <1000 /mm^3.
  • Part C Eligibility
  • All patients who completed Part B will be eligible for Part C unless significant safety concerns have been raised.
  • Participants must be able and willing to sign the Extension ICF.
  • Neither the Study Doctor or the participant will be informed of which drug (active or placebo) received during Part B.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Augusta University

    Augusta, Georgia, 30912

  • John Hopkins University

    Baltimore, Maryland, 21287

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of North Carolina

    Chapel Hill, North Carolina, 27514

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Texas - Southwestern

    Dallas, Texas, 75390

  • University of Colorado

    Denver, Colorado, 80045

  • University of California - Los Angeles

    Los Angeles, California, 90095

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Utah Medical Center

    Salt Lake City, Utah, 84132

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase II/III Randomized, Placebo Controlled, Double Blind Study to Evaluate the Effects of up to 24 Weeks of Low Dose Pazopanib on Hereditary Hemorrhagic Telangiectasia Related Epistaxis and Anemia

During the Efficacy Study (Part B), the investigators will study whether Pazopanib, taken daily for 24 weeks, will reduce the severity of nose bleeds in patients with hereditary hemorrhagic telangiectasia (HHT). Patients will either be provided active drug or a placebo [sugar - inactive pill], and be tested for nose bleed severity throughout the trial, including particularly nose bleed duration. Investigators will also test for blood loss, as well as for safety. This study is funded by the US Department of Defense USAMRAA and FDA/OOPD.

Read the detailed description

Now that a single dose pharmacokinetics (PK) study (Part A) has been completed to properly establish similar exposure with the prior pilot 50mg tablet, a double blind, placebo controlled study will follow (Part B), which proposes to define primarily the value of low dose (150 mg) Pazopanib on nose bleed duration, in the context of assessing perceived nose bleed severity.

After a patient completes Part B of the study, the patient will be invited to take part in an Extension Study (Part C) in which the patient will be provided with active drug equal to the dose they were assigned in Part B. All patients in Part C will receive active drug for 24 weeks. Part C will further assess the effects of Pazopanib on the severity of nose bleeds in patients with HHT and also support safety and efficacy elements.

After the patient completes their treatment period (either Part B or Parts B and C), a 12 week follow-up period will follow to support safety and efficacy elements. Secondary endpoints will be assessed, including ongoing blood loss, use of iron and blood products, quality of life, and drug safety.

Being tested
Pazopanib, Placebo oral capsule
Keywords
Osler-Weber-Rendu, Hereditary Hemorrhagic Telangiectasia, Patient Reported Outcome, HHT, Anemia, Nosebleed, Epistaxis
Medical subject headings
Telangiectasia, Hereditary Hemorrhagic, Epistaxis, Anemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PazopanibDrug

    Also called Votrient

    gel capsule, with 25mg-similar fills

  • Placebo oral capsuleDrug

    Also called cellulose capsule

    identical gel capsule without active pharmaceutical ingredient

Study groups in NCT03850964
Study groupRoleWhat they receive
Part B (Severe Anemia) Pazopanib - 150 mgActive comparator150 mg pazopanib oral capsules (six 25 mg placebo capsules daily).
Receives: Drug: Pazopanib
Part B (Severe Anemia) PlaceboPlacebo comparatorPlacebo oral capsules (six 25 mg placebo capsules daily).
Receives: Drug: Placebo oral capsule
Part B (Severe Epistaxis) Pazopanib - 150 mgActive comparatorPazopanib 150 mg oral daily dosing (six 25 mg Pazopanib capsules).
Receives: Drug: Pazopanib
Part B (Severe Epistaxis) PlaceboPlacebo comparatorPlacebo oral capsules (six 25 mg placebo capsules daily).
Receives: Drug: Placebo oral capsule
Part C Pazopanib - 150 mgExperimentalPazopanib 150 mg oral daily dosing (six 25 mg Pazopanib capsules).
Receives: Drug: Pazopanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in epistaxis duration in minutes

    >=50% decrease in the duration of epistaxis in the 150 mg pazopanib arm versus the placebo arm (moderate and severe cohorts combined)

    Measured: Average duration in weeks 19-24 (last 6 weeks of blinded phase) versus baseline.

  2. Hemoglobin Response rate increase in hemoglobin

    Increase in hemoglobin by ≥ 2 g/dl in the 150 mg pazopanib arm versus the placebo arm (moderate and severe cohorts combined)

    Measured: Average duration in weeks 19-24 (last 6 weeks of blinded phase) versus baseline.

Secondary outcomes (5)

  1. Achievement of meaningful improvement in epistaxis for HHT patients

    Compare patients reported being bothered by epistaxis at baseline and report not bothered at week 24

    Measured: Baseline [screening, run-in and 0 time points] and week 24.

  2. Percent change in blood transfusion rate in the Severe Cohort

    Reduction in RBC transfusion rate by at least one unit

    Measured: Baseline, and weeks 13-24

  3. Assess the safety of up to 24 and 48 weeks of treatment of pazopanib

    • AEs; absolute values and changes over time of hematology, clinical chemistry, urinalysis, blood pressure, and heart rate.
    • Physical exam, leg and abdominal evaluations, and CNS symptoms.
    • ECG parameters (PR, QRS, QT, QTc intervals) in addition to cardiac echocardiogram to evaluate LV function from pre-dose values in at-risk patients (baseline EF <50)

    Measured: 1st dose of intervention until Weeks 24 and 48

  4. Assess pharmacokinetics and pharmacodynamics (PK/PD) of treatment

    • Cτ, data permitting
    • Graphical exploration of PK/PD relationships between pazopanib and selected PD endpoints

    Measured: Weeks 12, 24, 36 and 48

  5. Establish comparability of endpoint outcomes for each hemoglobin stratification

    Trends for primary endpoint in severe (hemoglobin (<9.5 g/dl) and moderate (9.5-10.9 g/dl) groups.

    Measured: Baseline, Weeks 19-24, Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2019
  2. Study start8 May 2023
  3. Primary completion21 Nov 2025
  4. Study completion26 Aug 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
After at least a 6-week baseline period, participants will be assigned low dose pazopanib (150 mg) or placebo. At the termination of the 24-week Efficacy study participants will be provided the option to advance into an open label extension program including 24 weeks of treatment, followed by a 12-week non-drug follow up period. The extension would be on active drug, but otherwise blinded to the dose provided in the primary trial. This decision to continue into the extension will be based on a physician-participant discussion of any efficacy and safety concerns at week 24. A decision would be reached whether to proceed into the extension study and whether to consider a dose modification. A top dose of 150 mg will be maintained. After the extension, a 12 week follow-up time period will continue assessments to define maintenance of effect, and/ or relapse.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03850964
Sponsor's protocol ID
HT2
Other IDs
CDMRP-PR203473, 1R01FD006840-01A1
Acronym
Paz
Status last verified
Oct 2026
First submitted
12 Feb 2019
Last updated
27 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Over the first 18 months post study, the participating sites and PI's will produce primary and adjunct reports. After this period, study data will be posted on an available internet site for others to interrogate

Publications

  • Clark M, Berry P, Martin S, Harris N, Sprecher D, Olitsky S, Hoag JB. Nosebleeds in hereditary hemorrhagic telangiectasia: Development of a patient-completed daily eDiary. Laryngoscope Investig Otolaryngol. 2018 Nov 14;3(6):439-445. doi: 10.1002/lio2.211. eCollection 2018 Dec.

    PubMed 30599027

  • Parambil JG, Gossage JR, McCrae KR, Woodard TD, Menon KVN, Timmerman KL, Pederson DP, Sprecher DL, Al-Samkari H. Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia. Angiogenesis. 2022 Feb;25(1):87-97. doi: 10.1007/s10456-021-09807-4. Epub 2021 Jul 22.

    PubMed 34292451

  • Faughnan ME, Gossage JR, Chakinala MM, Oh SP, Kasthuri R, Hughes CCW, McWilliams JP, Parambil JG, Vozoris N, Donaldson J, Paul G, Berry P, Sprecher DL. Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia. Angiogenesis. 2019 Feb;22(1):145-155. doi: 10.1007/s10456-018-9646-1. Epub 2018 Sep 6.

    PubMed 30191360

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Pazopanib in people with Hereditary Hemorrhagic Telangiectasia and Epistaxis, run by Cure HHT at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in epistaxis duration in minutes (time frame: Average duration in weeks 19-24 (last 6 weeks of blinded phase) versus baseline.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03850964, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in