History of anemia of any cause other than HHT-related bleeding, or any other clinically significant inherited bleeding disorder aside from HHT.
History of hemorrhage from untreated pulmonary AVMs manifesting as hemoptysis or hemothorax within 12 weeks before screening.
Known cerebral, pulmonary, or hepatic AVMs that in the assessment of the investigator are recommended for or are planned for interventional treatment (including but not limited to endovascular embolization, stereotactic radiosurgery, surgical resection, or hepatic artery procedures) or that in the opinion of the investigator are likely to require such intervention during trial participation. Treated and clinically stable pulmonary, hepatic, or cerebral AVMs are not exclusionary.
History of clinically significant macroscopic (gross) hematuria within 12 weeks prior to screening, excluding hematuria attributable to a transient, resolved condition, eg, urinary tract infection, nephrolithiasis, recent urologic instrumentation.
GI bleeding due to non-HHT disease (eg, GI ulcers, diverticulosis), in the opinion of the investigator, within 6 months before screening.
Uncontrolled hypertension despite optimal medical management in the opinion of the investigator.
Known clinically significant cardiovascular disease, including but not limited to myocardial infarction, acute coronary syndrome, or coronary revascularization procedure in the 12 months prior to screening; current symptomatic heart failure (NYHA Class III and IV; patients with Class II heart failure may be enrolled after sponsor medical monitor review and agreement).
History of allergic reaction to any component of or excipient in the study drug.
History of active malignancy within 5 years before the screening visit, except for fully excised or treated basal cell carcinoma, cervical carcinoma in situ, or squamous cell carcinomas of the skin.
Has undergone liver transplantation or is anticipated to be on an active liver transplantation waiting list during the study treatment period.
Has HIV infection with a history of an AIDS-defining opportunistic infection or uncontrolled HIV infection with CD4+ count of <350 cells/µL, based on testing performed at the screening visit.
Has hepatitis B virus (HBV) infection with active disease, defined as hepatitis B surface antigen positive with detectable HBV DNA, unless on antiviral therapy with undetectable HBV DNA at screening; or has hepatitis C virus infection with viral load above the limit of quantification at screening.
Has active tuberculosis infection at screening.
History of alcohol use disorder or substance use disorder within the 12 months before screening that, in the opinion of the investigator, would interfere with compliance with study procedures or follow-up visits.
Medical conditions or comorbidities that, in the opinion of the investigator, would interfere with study compliance or data interpretation; or, in the opinion of the Investigator, taking part in the study would jeopardize the safety of the patient.
Initiation or dose modification of oral iron supplementation within 12 weeks prior to screening or during the observation period. Patients on a stable dose of oral iron supplementation for ≥12 weeks prior to screening are eligible. If a participant meeting other eligibility criteria has had a change (including initiation or discontinuation) in their oral iron dose within 12 weeks prior to screening or during the observation period, they may be enrolled in the study after review with the sponsor medical monitor.
Systemic use of a drug with antiangiogenic properties (including but not limited to bevacizumab, pazopanib, thalidomide, pomalidomide, lenalidomide, tamoxifen, raloxifene, bazedoxifene, AKT inhibitor drugs, receptor tyrosine kinase inhibitor drugs) within 12 weeks or within 5 half-lives, whichever is shorter, prior to screening or during the observation period.
Initiation or dose modification of an antifibrinolytic agent such as tranexamic acid or epsilon-aminocaproic acid in the 7 days prior to screening or during the observation period. Patients on a stable dose of an oral antifibrinolytic agent for ≥7 days prior to screening are eligible.
Use of a somatostatin analog (eg, octreotide, lanreotide) within 12 weeks prior to screening or during the observation period.
Initiation or dose modification of an anticoagulant (including but not limited to warfarin, apixaban, rivaroxaban, dabigatran) within 12 weeks prior to screening or during the observation period. Patients on a stable dose of an anticoagulant for ≥12 weeks prior to screening are eligible. Low-dose aspirin (≤100 mg once daily) for antiplatelet effect is allowed. Prophylactic-dose low molecular weight heparin (eg, enoxaparin ≤40 mg once daily, dalteparin ≤5000 units once daily, or equivalent) is allowed.
NOTE: For patients on warfarin, international normalized ratio (INR) must be within the therapeutic target range (TTR) at screening. If the INR is not within TTR at screening, patient may be enrolled if warfarin anticoagulation is assessed as stable in the clinical judgement of the investigator.
Initiation or dose modification of an erythropoiesis-stimulating agent (eg, epoetin alfa, darbepoetin alfa) within 12 weeks prior to screening or during the observation period. Patients on a stable dose of an erythropoiesis-stimulating agent for ≥12 weeks prior to screening are eligible.
Receipt of any vaccination within 2 weeks prior to first dose.
Recent major surgery (within 4 weeks before the screening visit) or planned major surgery during the study.
Any interventional procedure for AVMs performed within 2 weeks prior to screening or during observation period, including but not limited to pulmonary or cerebral AVM embolization. Patients who have undergone such procedures must have returned to clinical baseline, as determined by the investigator, prior to enrollment.
GI endoscopic intervention for telangiectasia or interventional procedure on nasal telangiectasias or for HHT-related epistaxis (including but not limited to nasal endovascular embolization; nasal laser [eg, potassium titanyl phosphate, neodymium: yttrium-aluminum-garnet, or diode laser] ablation performed under general or regional anesthesia; septodermoplasty; surgical closure of the nares) within 8 weeks prior to screening or during the observation period. Patients must have returned to clinical baseline as determined by the investigator prior to enrollment.
Received an investigational agent within the last 30 days or 5 half-lives, whichever is longer, before screening; or is concurrently enrolled in or plans to enroll in another interventional clinical study while participating in this study.
Any of the following laboratory abnormalities:
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) >2× the upper limit of normal (ULN), or total bilirubin >1.5×ULN.
NOTE: Patients with elevated liver enzymes attributable to HHT-related hepatic AVMs, confirmed by hepatic imaging, may be considered for enrollment after agreement with the sponsor medical monitor. Patients with elevated unconjugated bilirubin that is secondary to documented Gilbert syndrome are eligible if conjugated bilirubin is ≤1.5×ULN.
Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 (calculation based on the Chronic Kidney Disease Epidemiology Collaboration creatinine equation)
Hemoglobin <7 g/dL at screening Note: Patients who fail this criterion acutely (eg, in the context of a recent bleeding episode prior to receipt of scheduled hematologic support) may be eligible to rescreen once hematologic stability has been achieved, at the discretion of the investigator and after discussion with the sponsor medical monitor.
Absolute neutrophil count <1500/mm3
A social circumstance that in the opinion of the investigator or delegate or sponsor would impede compliance with or hinder completion of the study.