Pomalidomide for the Treatment of Bleeding in Hereditary Hemorrhagic Telangiectasia (PATH-HHT)

  • End date
    Sep 1, 2023
  • participants needed
  • sponsor
    The Cleveland Clinic
Updated on 21 October 2022
platelet count
blood transfusion
parenteral infusion


This is a Phase II placebo-controlled double-blind study of pomalidomide in patients with hereditary hemorrhagic telangiectasia (HHT) with moderate to severe epistaxis who have anemia and/or require parenteral iron infusions or blood transfusions. A total of 159 patients will be randomized 2:1 to treatment with oral pomalidomide or matching placebo for 24 weeks. Mean change from baseline to 24 weeks in the Epistaxis Severity Score (ESS) will be compared between treatment groups to determine pomalidomide efficacy.


HHT is associated with substantial morbidity, leading to a reduced quality of life, decreased rate of employment and a high incidence of depression. There currently exists no medical therapy recognized as consistently efficacious in HHT. Reports of the efficacy of thalidomide in HHT, as well as interim results of a pilot trial of pomalidomide in HHT provide evidence of efficacy with minimal toxicity. The favorable efficacy:toxicity ratio of pomalidomide suggest that it may benefit patients with HHT.

This study is designed as a Phase II placebo-controlled double-blind study of pomalidomide in HHT patients with moderate to severe epistaxis who have anemia and/or require parenteral iron infusions or blood transfusions. A total of 159 patients will be randomized 2:1 to treatment with oral pomalidomide or matching placebo for 24 weeks.

Primary Objective: To determine efficacy of pomalidomide compared to placebo for the reduction in severity of epistaxis after 24 weeks of treatment.

Secondary Objectives: To determine the safety and tolerability of pomalidomide for the treatment of HHT; to determine if pomalidomide treatment improves quality of life in HHT; to determine whether a continued response to pomalidomide is evident 4 weeks after treatment discontinuation; to develop a biorepository for future studies to define biomarkers predictive of pomalidomide response and allow investigations into the biology of HHT and mechanisms of pomalidomide.

Condition Telangiectasia, Hereditary Hemorrhagic
Treatment Placebo oral capsule, Pomalidomide Oral Product
Clinical Study IdentifierNCT03910244
SponsorThe Cleveland Clinic
Last Modified on21 October 2022


Yes No Not Sure

Inclusion Criteria

A clinical diagnosis of HHT as defined by the Curacao criteria
Age > 18 years
Platelet count ≥ 100,000/µl
WBC ≥ 2,500/µl
INR ≤ 1.4 and normal ± 2 sec activated partial thromboplastin time (aPTT or PTT per local laboratory designation) by local laboratory criteria (except for patients on a stable dose of warfarin or direct oral anticoagulants)
Epistaxis severity score ≥ 3 measured over the preceding three months, measured at the screening visit
A requirement for anemia, as determined by local laboratory hemoglobin assessment and normal ranges, and/or parenteral infusion of at least 250 mg of iron or transfusion of 1 unit of blood over the 24 weeks preceding the screening visit
Females of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing (once very two weeks) as required in the POMALYST REMS program. FCBP must a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy
Ability to understand and sign informed consent
All study participants must agree to be registered into the FDA mandated POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program

Exclusion Criteria

Women currently breast feeding
Renal insufficiency, serum creatinine > 2.0 mg/dl
Hepatic insufficiency, bilirubin > 2.0 (or >4.0 in the setting of a prior clinical or genetic diagnosis of Gilbert's syndrome) or transaminases > 3.0x normal
Prior treatment with thalidomide or other imid drugs within previous 6 months
Prior treatment with bevacizumab (systemic or nasal) within previous 6 weeks
Prior treatment with pazopanib within previous 6 weeks
The use of octreotide or oral estrogens within the previous month
Peripheral neuropathy, confirmed by neurologic consultation
History of prior unprovoked thromboembolism confirmed by venous ultrasound or other imaging modalities
Known underlying hypoproliferative anemia (i.e. myelodysplasia, aplastic anemia)
Currently enrolled in other interventional trials
Known hypersensitivity to thalidomide or lenalidomide
The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
Known SMAD-4 mutation, unless there has been a colonoscopy with normal (negative) results, or in which the patient has had no more than 5 small (in the opinion of the gastroenterologist) colonic polyps completely removed within the preceding 18 months
Anything that in the investigator's opinion is likely to interfere with completion of the study
Use of these treatments is not permitted during study participation
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