Pazopanib Effects on Bleeding in Hereditary Hemorrhagic Telangiectasia (Paz)
|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: NCT03850964|
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 Nosebleed Anemia||Drug: Pazopanib Drug: Placebo oral capsule||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||After at least a 3wk baseline period, patients will be assigned low dose drug or placebo. After 3mths of therapy, if epistaxis duration endpoint has been reached, the drug dose will remain the same… However, if this end point is not reached, and no safety signals have been observed, the dose can be advanced up to double the initial dose. A strong initial trend would still permit continuance of the low dose intervention. Post-study drug discontinuance, a 3 month follow-up time period will continue assessments to define maintenance of effect, and/ or relapse. An interim to adjust total subject number, and potential futility occurs after 12 patients have completed their 24 week dosing period.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Project Manager in operation will also be masked.|
|Official Title:||Randomized Double Blind Study to Evaluate the Effect of Low Dose Pazopanib on Bleeding Due to Hereditary Hemorrhagic Telangiectasia|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||March 2021|
Active Comparator: Pazopanib
Pazopanib 50mg oral daily dosing [two 25mg capsules]. If after 3mths primary endpoint not achieved, and safety is maintained, consideration for advance in dose to up to 100mg daily
gel capsule, with 25mg-similar fills
Other Name: Votrient
Placebo Comparator: Placebo oral capsule
Drug: Placebo oral capsule
identical gel capsule without active pharmaceutical ingredient
Other Name: cellulose capsule
- Change in epistaxis duration in minutes [ Time Frame: Cumulative duration of last 3weeks of 24week Rx period compared to last 3 weeks of baseline ]A daily electronic recording of each bleed, with start and end times to define per-bleed duration, over the drug dosing period of the study.
- Change in average gushing frequency [ Time Frame: Cumulative number of gushing bleeds baseline 3weeks, and weeks 22-24. ]Patient rated intensity of each bleed, as in 0 or 1, averaged over the 3wk periods
- Change in average bleed frequency [ Time Frame: Baseline 3 weeks, and weeks 22-24 ]Annotated by electronic record, number of bleeds per day, cumulative amount over 3 week periods.
- Absolute [gm/dl] change in average serum hemoglobin levels [ Time Frame: Baseline [screening, run-in and 0 time points] and week 22 and week 24. ]Serum values drawn every 3wks
- Percent change in blood transfusion frequency [ Time Frame: Baseline 6 weeks and weeks 19-24 weeks ]Total packed red blood cells over 6 week periods
- Percent change in IV iron infusion frequency [ Time Frame: Baseline 6 weeks and weeks 19-24 of study ]IV iron infusion administration over 6 week periods.
- Change in the averaged daily per bleed epistaxis severity [ Time Frame: Baseline 3 weeks and last 3 weeks [weeks 22-24] of the study ]A specific query on "severity" [0-10] will be asked daily or for each bleed within the current patient reported outcome and averaged over 3 week periods.
- Establish the presence of an Active/ safe serum trough drug concentration [ Time Frame: baseline, 3, 6, 12, and 24 weeks. ]Samples will be sent for Pazopanib concentrations during the trial, steady state achieved within 3 weeks of time.
- Change in composite mental quality of life score [ Time Frame: baseline, 12 and 24 weeks ]Short Form Health Survey 36 [range 0-100; with increase suggesting improvement in self-reported perception of mental health [change of 7 points considered clinically relevant]
- Increase/ improvement in composite physical quality of life score [ Time Frame: baseline, 12 and 24 weeks ]Short Form Health Survey 36 [range 0-100, with higher values representing improvement in self-reported perception of physical health; 7 point change considered clinically significant]
- Monitor for a rise in Systolic blood pressure [ Time Frame: Daily during the on-drug portion of the study; 24 weeks ]Daily electronic measurements, mm mercury, will be evaluated to assess upward trends as part of a safety monitoring, with triggers at 20mm mercury rise, or surpassing bp 140 mm mercury.
- Monitor for a rise in Diastolic blood pressure [ Time Frame: Daily during the on-drug portion of the study; 24 weeks ]Daily electronic measurements, mm mercury, will be evaluated to assess upward trends as part of safety monitoring, with triggers at 10mm mercury rise, or surpassing bp 90mm mercury.
- Monitor for a fold rise in alanine aminotransferase [liver function test] elevation [ Time Frame: baseline and every 3 weeks for the 24 weeks of the on-drug portion of the trial ]This value will be apprised to monitor for safety, triggered to mandate a drug agent pause once the values reaches a 2 fold elevation
- Identify percent change in left ventricular ejection fraction [echo] in at risk patients [ Time Frame: baseline and 24 weeks. ]An evaluation of the ejection fraction of the left ventricle will be compared at baseline, and those below 50% will also have one done at 24 weeks to identify reductions of 15% or greater...
- Characterize any change in Iron stores [ Time Frame: baseline and 24 weeks. ]Ferritin [normal serum values of 12 ug/ ml to 150 ug/ ml in females, 300 ug/ ml in males]. However, values in below 30 ug/ ml can limit erythropoiesis.
- Elucidate changes in Left ventricular stress [ Time Frame: baseline and 24 weeks. ]NTproBNP serum assay which serves as a surrogate for left ventricular stress. Values <125 pg/ml is considered normal, with values above 300 pg/ml considered high/ consistent with elements of heart failure.
- Change in fatigue composite score [ Time Frame: Baseline and 24 weeks. ]Patient Reported Outcome Measurement Information System-fatigue queries [0-100 range; targets level of fatigue and impact on physical functioning; 5 point change considered clinically significant.
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): NCT03850964
|Contact: Nicole Schaeferemail@example.com|
|Contact: DENNIS L MD SPRECHER, MDfirstname.lastname@example.org|
|Principal Investigator:||James Gossage, MD||Geogia Health Sciences University|