Clinical trial NCT07018401: Pomalidomide for the Treatment of Bleeding in Hereditary Hemorrhagic Telangiectasia Longitudinal Assessment Study
Official title: Pomalidomide for the Treatment of Bleeding in Hereditary Hemorrhagic Telangiectasia After Trial Longitudinal Assessment Study (PATH-HHT ATLAS)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Hereditary Hemorrhagic Telangiectasia (HHT)
Keywords: hereditary hemorrhagic telangiectasia
HHT
Osler-Weber-Rendu
pomalidomide
PATH-HHT
PATH-HHT ATLAS
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: The Cleveland Clinic
name: University of North Carolina, Chapel Hill
name: University of California, San Francisco
name: Mayo Clinic
name: University of Utah
name: University of California, San Diego
name: University of Florida
name: Medical College of Wisconsin
name: Johns Hopkins University
name: University of Pennsylvania
First posted: 2025-06-12
Enrollment: 62
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with hereditary hemorrhagic telangiectasia and moderate-to-severe bleeding who previously enrolled in the PATH-HHT trial

Brief summary: This is a multicenter U.S. longitudinal study evaluating patients with hereditary hemorrhagic telangiectasia who participated in the PATH-HHT clinical trial of pomalidomide for the treatment of HHT. This study is a longitudinal assessment of safety and effectiveness of pomalidomide in HHT in clinical trial participants following completion of the double-blind, placebo-controlled study.

Detailed description: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant condition characterized by disordered angiogenesis that affects 1 in 5,000 people. It results in numerous clinical complications including severe recurrent epistaxis, gastrointestinal bleeding, chronic iron deficiency anemia (and possible transfusion dependence), high-output cardiac failure, and many others. In recognition that elevated levels of vascular endothelial growth factor (VEGF) are elevated in HHT, anti-angiogenic drugs are now being used to treat HHT off-label to manage HHT-associated bleeding. A primary agent used for this purpose is pomalidomide, an oral immunomodulatory drug with antiangiogenic properties. Pomalidomide was demonstrated to be efficacious over a 6-month treatment period in the multicenter U.S. randomized controlled PATH-HHT Study. The present study is the successor to PATH-HHT, the PATH-HHT ATLAS (After Trial Longitudinal Assessment Study). This study will evaluate the long-term impact of pomalidomide on epistaxis (as measured by the validated ESS, epistaxis severity score), gastrointestinal bleeding, and iron deficiency anemia (as assessed by hemoglobin measurements, red blood cell transfusions, and intravenous iron infusions).

Eligibility criteria: Inclusion Criteria:

1. A clinical diagnosis of HHT as defined by the Curacao criteria
2. Age \> 18 years
3. Platelet count ≥ 100 x 109/L prior to pomalidomide initiation
4. WBC ≥ 2.5 x 109/L prior to pomalidomide initiation
5. INR ≤ 1.4 and normal ± 2 sec activated partial thromboplastin time (aPTT) by local laboratory criteria (except for patients on a stable dose of warfarin or direct oral anticoagulants)
6. Epistaxis severity score ≥ 3 measured over the preceding month
7. A requirement for anemia, as determined by local laboratory 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
8. 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
9. Females of childbearing potential (FCBP)† must adhere to the pregnancy testing schedule mandated by the POMALYST REMS program
10. Prior enrollment on PATH-HHT study (NCT03910244)

    * A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Exclusion Criteria:

1. Women currently breast feeding or pregnant
2. Renal insufficiency, serum creatinine \> 2.0 mg/dl
3. 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
4. Prior treatment with thalidomide or other non-pomalidomide immunomodulatory imide drugs (IMiDs) within previous 6 months
5. Prior treatment with bevacizumab (systemic or nasal) within previous 6 weeks
6. Prior treatment with pazopanib within previous 6 weeks
7. The use of octreotide or estrogens within the previous month
8. History of prior unprovoked thromboembolism confirmed by venous ultrasound or other imaging modalities
9. Known peripheral neuropathy, confirmed by neurologic consultation
10. Known underlying hypoproliferative anemia (i.e. myelodysplasia, aplastic anemia)
11. Currently enrolled in other drug trials
12. Known hypersensitivity to thalidomide or lenalidomide
13. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
14. 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
15. Anything that in the investigator's opinion is likely to interfere with completion of the study

Primary outcomes:
measure: Epistaxis Severity Score
timeFrame: 12 months
Secondary outcomes:
measure: Serum hemoglobin (g/dL)
timeFrame: 12 months
measure: Hematologic Support Score
timeFrame: 12 months
measure: Intravenous iron infusion (mg elemental iron)
timeFrame: 12 months
measure: Red cell transfusion (units of packed red blood cells)
timeFrame: 12 months
measure: Incidence of treatment-emergent adverse events (safety)
timeFrame: 12 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California-San Diego
state: California
city: San Francisco
country: United States
facility: University of California-San Francisco
state: California
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina, Chapel HIll
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Stanford University
name: Ellen Zhang, MD
role: STUDY_DIRECTOR
References: