Clinical Trials

Inclusion Criteria:

• A definite diagnosis of hereditary hemorrhagic telangiectasia is 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 definite diagnosis of hereditary hemorrhagic telangiectasia is defined as having a gene sequencing diagnosis of hereditary hemorrhagic telangiectasia:
  • Epistaxis due to hereditary hemorrhagic telangiectasia at least 2 x per week, for a  cumulative duration of at least 25 minutes per week;
  • 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);
  • 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.
• Male or female [non-child bearing potential].

Exclusion Criteria:  

• 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.
• 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.
• QT corrected interval ≥ 450 msec, based on averaged QT corrected interval values of triplicate ECGs obtained over a brief recording period.
• Hemoglobin < 6 g/dL.
• Platelets < 100 x 10^9/L.  
• International normalized ratio (INR) >1.2 x upper limit of normal and activated partial  thromboplastin time (aPTT) > 1.2 x upper limit of normal.  
• Alanine Transaminase > 2 x upper limit of normal.
• Bilirubin > 1.5 x upper limit of normal (isolated bilirubin > 1.5 x 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.  
• Substantive renal disease (eGFR < 30 mL/min/1.73m^2 calculated 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/mm^3.

Eligibility last updated 10/5/21. Questions regarding updates should be directed to the study team contact.