# 1/2 Pomalidomide for Bleeding in Patients with Hereditary Hemorrhagic Telangiectasia (HHT)

> **NIH NIH UH3** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $887,209

## Abstract

ABSTRACT
Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder characterized by diffuse arteriovenous
malformations (AVMs) and telangiectasia that affect many organs. The most common manifestations of HHT are
epistaxis and GI bleeding; however AVMs that involve the lungs, brain or liver can also lead to devastating
cardiovascular complications including congestive heart failure, pulmonary hemorrhage and hemorrhagic stroke.
Estimates suggest a prevalence of more than 100,000 cases of HHT in the US. In addition to bleeding and
cardiovascular manifestations, the morbidity of HHT leads to a high incidence of anxiety and depression that
greatly affects social function. There is no broadly-accepted, effective therapy for HHT. Ablation of HHT lesions
via interventional approaches is commonly used but provides only transient benefit. Medical approaches have
included anti-fibrinolytic therapy, estrogen, and octreotide, among others, however these are not effective in
most patients. A recent study demonstrated that nasal sprays containing tranexamic acid, estriol or bevacizumab
were no more effective than placebo in treating HHT-associated epistaxis. The current study builds upon results
of several small studies that suggest efficacy of thalidomide in HHT; however, thalidomide is not available for
clinical trials in the U.S. Thus, we propose to study pomalidomide, a third generation thalidomide analogue with
similar anti-angiogenic activity but less toxicity that thalidomide. A small, industry-funded pilot study by the PI
has demonstrated efficacy and safety of pomalidomide in HHT, and the FDA has issued an IND to expand these
observations. This resubmission proposes a randomized, placebo-controlled study developed with support from
an NHLBI U34 Clinical Trial Planning Grant and U24 Clinical Trials Development Resource for Hematologic
Disorders by a team of HHT experts, a patient advocate, and experienced clinical trial statisticians. The same
team that designed the study will conduct it, using a sIRB at the Cleveland Clinic. We propose to 1) determine
the efficacy and safety of pomalidomide in patients with HHT and epistaxis requiring periodic iron infusion or
blood transfusion, 2) determine the effect of pomalidomide on quality of life in patients with HHT using NIH
PROMIS tools and an HHT-specific questionnaire, and 3) create a biorepository of samples from study patients
for future biomarker and mechanistic studies. This study may validate pomalidomide as a new therapeutic option
and change the paradigm for treatment of HHT.

## Key facts

- **NIH application ID:** 10385804
- **Project number:** 5UH3HL140097-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Keith R. McCrae
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $887,209
- **Award type:** 5
- **Project period:** 2020-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10385804

## Citation

> US National Institutes of Health, RePORTER application 10385804, 1/2 Pomalidomide for Bleeding in Patients with Hereditary Hemorrhagic Telangiectasia (HHT) (5UH3HL140097-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10385804. Licensed CC0.

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