Pazopanib for the Treatment of Epistaxis in Hereditary Hemorrhagic Telangiectasia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|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]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|