Pazopanib for the Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia
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|ClinicalTrials.gov Identifier: NCT03850730|
Recruitment Status : Not yet recruiting
First Posted : February 22, 2019
Last Update Posted : February 22, 2019
|Condition or disease||Intervention/treatment||Phase|
|Hereditary Hemorrhagic Telangiectasia Epistaxis||Drug: Pazopanib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|Masking Description:||This is an open label study and thus all personnel and patients will be aware of the assignment.|
|Official Title:||An Open-label, Non-randomized Study of the Efficacy of Pazopanib for the Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||January 2024|
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.
Active pharmaceutical ingredient plus excipients filled into a capsule for the lower dosing necessary in this study
Other Name: Pazopanib capsule
- 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
- Percent change in average gushing frequency [ Time Frame: Last 3 weeks of drug period vs baseline 3 weeks; over 16-24 weeks of dosing ]Patient rated intensity of each bleed, as in 0 or 1, averaged over 3 wk periods.
- Percent change in average bleed frequency [ Time Frame: Last 3 weeks compared to the baseline 3 weeks; over 16-24 weeks of dosing ]Annotated number of bleeds per day, and summed over 3 week periods
- 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 ]Serum values drawn every 3 weeks
- 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 ]Use of packed red blood cells over 6 week time periods.
- 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 ]Number of interval IV iron infusions in 6 week periods
- 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 ]Epistaxis severity score [0-10] housed in the current patient reported outcome instrument will be averaged
- 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. ]Patients rising above 140 mm mercury, or those who increase by 20 or more mm mercury will trigger protocol defined treatments.
- 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 ]Patients rising above 90 mm mercury, or those who increase by 10 mm mercury or more will trigger protocol defined treatments.
- Number of participants with changes in alanine aminotransferase [liver function test] [ Time Frame: Baseline and throughout the 16-24 week dosing period ]measurement every 3 weeks to evaluate fold increase with use of drug
- 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 ]Assays to be analyzed to evaluate the exposures done to remain within safe and effective range [1ug/ ml to 10ug/ml].....
- 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 ]short form health survey 36 [range 1-100, higher number representing better self-reported mental health]
- 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. ]short form health survey 36 [range 1-100, higher number representing better self-reported physical health]
- Evaluate for change in fatigue composite scores [ Time Frame: baseline and study end; up to 24 weeks ]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.
- Interrogate levels of Iron stores [ Time Frame: baseline and at on-drug study end; 16, 20 or 24 weeks depending on study duration ]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]
- Characterize change in left ventricular stress [ Time Frame: baseline and on-drug study end; 16, 20 or 24 weeks depending on study duration] ]NTproBNP serum values represent a surrogate for left ventricular stress [<125pg/ml normal, while above 350pg/ml high and potentially consistent with heart failure]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03850730
|Contact: Nicole Schaeferfirstname.lastname@example.org|
|Contact: Dennis L Sprecher, MDemail@example.com|
|Principal Investigator:||Raj Kasthuri, MD||University of North Carolina|