Hereditary Hemorrhagic TelangiectasiaPhase 1/2NCT03850730
Pazopanib for the Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia
A Phase 1/2 study testing Pazopanib in people with Hereditary Hemorrhagic Telangiectasia and Epistaxis, run by Cure HHT.
Trial 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 more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hereditary Hemorrhagic Telangiectasia, Epistaxis
- What is being tested?
- Pazopanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2023to 31 Dec 2025
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 2. Epistaxis due to hereditary hemorrhagic telangiectasia at least 2x per week, for a cumulative duration of at least 25 minutes per week
- 3. 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).
- 4. 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.
- 5. Male or female [non-child bearing potential]
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 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).
- Currently has perfused pulmonary AVMs with feeding artery diameter >3mm.
- Known significant bleeding sources other than nasal or gastrointestinal.
- Systemic use of a vascular endothelial growth factor inhibitor in the past 3 months or previous enrollment in this study.
- Active and recent onset of clinically significant diarrhea.
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- 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 the period to include active treatment and 6 weeks of follow up.
- 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.
- QTc ≥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.]
- Hgb <6 g/dL.
- Platelets < 100x109/L.
- International normalized ratio (INR) >1.2x upper limit of normal and activated partial thromboplastin time (aPTT)>1.2x upper limit of normal.
- Alanine Transaminase >2x 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. 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.]
- Substantive renal disease (eGFR <30 mL/min/1.73m2calculated using the Cockcroft-Gault formula)
- Echo derived left ventricular ejection fraction <30%.
- Thyroid stimulating hormone > upper limit of normal.
- Urine protein to creatinine ratio >0.3.
- Neutrophil count <1500/mm3.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: An Open-label, Non-randomized Study of the Efficacy of Pazopanib for the Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
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.
- Conditions
- Hereditary Hemorrhagic Telangiectasia, Epistaxis
- Being tested
- Pazopanib
- Keywords
- osler-weber-rendu, nose bleeds, open label, HHT, Pazopanib
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic, Epistaxis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Also called Pazopanib capsule
Active pharmaceutical ingredient plus excipients filled into a capsule for the lower dosing necessary in this study
| Study group | Role | What they receive |
|---|---|---|
| Pazopanib | Experimental | 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. Receives: Drug: Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Summed minutes of bleeding at baseline 3 weeks and the last 3 weeks of dosing, over16-24 weeks of dosing
Secondary outcomes (13)
Percent change in average gushing frequency
Patient rated intensity of each bleed, as in 0 or 1, averaged over 3 wk periods.
Measured: Last 3 weeks of drug period vs baseline 3 weeks; over 16-24 weeks of dosing
Percent change in average bleed frequency
Annotated number of bleeds per day, and summed over 3 week periods
Measured: Last 3 weeks compared to the baseline 3 weeks; over 16-24 weeks of dosing
Absolute [gm/dl] change in serum hemoglobin
Serum values drawn every 3 weeks
Measured: comparing last 6 weeks to baseline 3-6 weeks; over 16-24 weeks of drug dosing
Change in the frequency of blood transfusions
Use of packed red blood cells over 6 week time periods.
Measured: Final 6 weeks of study, compared to baseline 3-6 weeks; over 16- 24 weeks of dosing
Change in the frequency of IV iron infusions
Number of interval IV iron infusions in 6 week periods
Measured: Last 6 weeks of dosing to first 6 weeks; over 16-24 weeks of drug administration
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
Measured: The final 3 weeks to the baseline 3 weeks of the study; for a16-24 week duration study
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.
Measured: Daily from baseline through up to 24 weeks till on-drug study completion.
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.
Measured: Daily from baseline through up to 24 weeks till on-drug study completion
Number of participants with changes in alanine aminotransferase [liver function test]
measurement every 3 weeks to evaluate fold increase with use of drug
Measured: Baseline and throughout the 16-24 week dosing period
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].....
Measured: Over 16-24 week duration of study; once at steady state for each administered dose
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]
Measured: baseline, week 12 and at study drug-dosing end; 16, 20 or 24weeks
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]
Measured: baseline, week 12 and at study drug-dosing end; up to 24 weeks.
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.
Measured: baseline and study end; up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2019
- Study start1 Jul 2023 (estimated)
- Primary completion30 Jun 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Hemorrhagic TelangiectasiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- After at least a 6 week baseline, patients will be placed on very low dose Pazopanib \[25mg-similar\], for 8 weeks.. If the primary bleeding duration endpoint is achieved, than the patient will continue for another 8wks, or a total of 16 weeks on the same dose. Lack of any response will result in a dose advance to 50mg for another 3mths. If a moderate change has occurred, than the 25mg dose will be continued for another 4 weeks, and if primary endpoint achieved, continue for another 12 weeks... Lack of endpoint achievement, will augment dose to 50mg and extend study for 12 weeks, or a total of 24 weeks.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cure HHT
- Sponsor type
- University, hospital or other
- Collaborators
- University of North Carolina
- Responsible party
- Sponsor
- Investigators
- Raj Kasthuri, MD, Principal investigator, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03850730
- Sponsor's protocol ID
- HT3
- Status last verified
- Sep 2022
- First submitted
- 12 Feb 2019
- Last updated
- 8 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: After the PI and associates produce the primary and adjunct reports, these data can be posted on data files for public access
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Non-randomized Study of the Efficacy of Pazopanib for the Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
- ClinicalTrials.gov ID
- NCT03850730
- Acronym / sponsor ID
- HT3
- Conditions
- Hereditary Hemorrhagic Telangiectasia, Epistaxis
- Keywords
- osler-weber-rendu, nose bleeds, open label, HHT, Pazopanib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Cure HHTUniversity, hospital or other
- Collaborators
- University of North Carolina
- Study start
- 1 Jul 2023 (estimated)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 22 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- After at least a 6 week baseline, patients will be placed on very low dose Pazopanib [25mg-similar], for 8 weeks.. If the primary bleeding duration endpoint is achieved, than the patient will continue for another 8wks, or a total of 16 weeks on the same dose. Lack of any response will result in a dose advance to 50mg for another 3mths. If a moderate change has occurred, than the 25mg dose will be continued for another 4 weeks, and if primary endpoint achieved, continue for another 12 weeks... Lack of endpoint achievement, will augment dose to 50mg and extend study for 12 weeks, or a total of 24 weeks.
| Arm | Type | Receives |
|---|---|---|
| Pazopanib | Experimental | Drug: PazopanibPazopanib, 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- a definite diagnosis of hereditary hemorrhagic telangiectasia defined as having at least 3 of the following criteria:
- 2. Epistaxis due to hereditary hemorrhagic telangiectasia at least 2x per week, for a cumulative duration of at least 25 minutes per week
- 3. 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).
- 4. 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.
- 5. Male or female [non-child bearing potential]
Key exclusion criteria (23 listed)
- 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 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).
- Currently has perfused pulmonary AVMs with feeding artery diameter >3mm.
- Known significant bleeding sources other than nasal or gastrointestinal.
- Systemic use of a vascular endothelial growth factor inhibitor in the past 3 months or previous enrollment in this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PazopanibAlso: Pazopanib capsuleActive pharmaceutical ingredient plus excipients filled into a capsule for the lower dosing necessary in this study | Drug | Pazopanib |
Primary outcome
Percent change in epistaxis duration in minutes
Time frame: Summed minutes of bleeding at baseline 3 weeks and the last 3 weeks of dosing, over16-24 weeks of dosing
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
13 secondary outcomes
Percent change in average gushing frequency
Time frame: Last 3 weeks of drug period vs baseline 3 weeks; over 16-24 weeks of dosing
Percent change in average bleed frequency
Time frame: Last 3 weeks compared to the baseline 3 weeks; over 16-24 weeks of dosing
Absolute [gm/dl] change in serum hemoglobin
Time frame: comparing last 6 weeks to baseline 3-6 weeks; over 16-24 weeks of drug dosing
Change in the frequency of blood transfusions
Time frame: Final 6 weeks of study, compared to baseline 3-6 weeks; over 16- 24 weeks of dosing
Change in the frequency of IV iron infusions
Time frame: Last 6 weeks of dosing to first 6 weeks; over 16-24 weeks of drug administration
Percent change in the per bleed average epistaxis severity
Time frame: The final 3 weeks to the baseline 3 weeks of the study; for a16-24 week duration study
Daily monitoring for change in systolic blood pressure [mm mercury] using daily recordings
Time frame: Daily from baseline through up to 24 weeks till on-drug study completion.
Daily monitoring for change in diastolic blood pressure [mm mercury]
Time frame: Daily from baseline through up to 24 weeks till on-drug study completion
Number of participants with changes in alanine aminotransferase [liver function test]
Time frame: Baseline and throughout the 16-24 week dosing period
Monitor for active and safe trough serum drug concentrations
Time frame: Over 16-24 week duration of study; once at steady state for each administered dose
Evaluate for change in composite mental quality of life scores
Time frame: baseline, week 12 and at study drug-dosing end; 16, 20 or 24weeks
Evaluate for change in composite physical quality of life scores
Time frame: baseline, week 12 and at study drug-dosing end; up to 24 weeks.
Evaluate for change in fatigue composite scores
Time frame: baseline and study end; up to 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2022.
- Individual participant dataSharing planned: Undecided. After the PI and associates produce the primary and adjunct reports, these data can be posted on data files for public access
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Raj Kasthuri, MD principal investigator
University of North Carolina
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pazopanib in people with Hereditary Hemorrhagic Telangiectasia and Epistaxis, run by Cure HHT.
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 10 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 8 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Nicole Schaefer (410-357-9932, nicole.schaefer@curehht.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent change in epistaxis duration in minutes (time frame: Summed minutes of bleeding at baseline 3 weeks and the last 3 weeks of dosing, over16-24 weeks of dosing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Sep 2022.