Bevacizumab In Hereditary Hemorrhagic Telangiectasia

NCT04404881 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 19-833
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is studying to see whether bevacizumab may treat chronic bleeding and iron deficiency anemia in Hereditary Hemorrhagic Telangiectasia (HHT). Hereditary Hemorrhagic Telangiectasia (HHT) is a disorder that causes abnormal blood vessel formation. In HHT, there is a mutation in the TGF-β pathway, which results in an increase of vascular endothelial growth factor (VEGF) levels. An increase in VEGF levels can result in poorly formed blood vessels that have a higher rate of bleeding than normal blood vessels. Bevacizumab is designed to block VEGF activity. It is believed that targeting increased VEGF levels may be able to treat HHT. This research study involves the following study drug: \- Bevacizumab

Conditions

Hereditary Hemorrhagic Telangiectasia

Keywords

Hereditary Hemorrhagic Telangiectasia

Outcome Measures

Primary Outcomes (1)

• Change in hematologic support score from pretreatment to maintenance

  The change in Hematologic Support Score (HSS) from pretreatment to maintenance will be evaluated with a paired t-test or a Wilcoxon signed-rank test, whichever is most appropriate for the distribution of the data. Presence of a statistically-significant difference (P\<0.05) will determine if the study achieves its primary outcome measure.

  36 Weeks

Secondary Outcomes (5)

• Difference in the individual patient mean hemoglobin

  36 Weeks

• Difference in the individual patient pRBC transfusion requirement

  36 Weeks

• Difference in the individual patient intravenous iron infusion requirement

  36 Weeks

• Average Maintenance Epistaxis Severity Score

  36 Weeks

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0.

  All patients will be evaluable for toxicity from the time of their first treatment with bevacizumab up to 36 weeks

Other Outcomes (3)

• HHT-specific Quality of Life Score (HHT-QoL) (exploratory)

  36 Weeks

• PROMIS Instruments (exploratory)

  36 Weeks

• Hematologic Impact Score (HIS) (exploratory)

  36 Weeks

Study Arms (1)

Bevacizumab

EXPERIMENTAL

* The research study procedures include: screening for eligibility, pretreatment period, study treatment, end-of-study visit, and follow-up visit. Each period consists of 12 weeks, for a total of 36 weeks. * Pretreatment Period:Hematologic Support: iron transfusions and red cell transfusions as determined by study doctor. * Induction Period (first 3 months of bevacizumab treatment): * Hematologic Support: iron transfusions and red cell transfusions as determined by study doctor. * Bevacizumab: once every 2 weeks via intravenous infusion for up to 12 weeks. * Maintenance Period (second 3 months of bevacizumab treatment): * Hematologic Support: Iron transfusions and red cell transfusions as determined by study doctor. * Bevacizumab: once every 4 weeks via intravenous infusion for up to 12 weeks.

Drug: Bevacizumab (Avastin®)

Interventions

Bevacizumab (Avastin®) DRUG

* Induction Period (first 3 months of bevacizumab treatment): \-- Bevacizumab: once every 2 weeks via intravenous infusion for up to 12 weeks. * Maintenance Period (second 3 months of bevacizumab treatment): * Bevacizumab: once every 4 weeks via intravenous infusion for up to 12 weeks.

Also known as: Avastin®

Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A clinical diagnosis of "possible/suspected" or "definite" hereditary hemorrhagic telangiectasia, as defined by presence of 2 or more of the Curacao criteria (spontaneous and recurrent epistaxis, telangiectasias at characteristic sites, visceral arteriovenous malformations (AVMs), first degree relative with HHT).
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of bevacizumab for HHT in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Red blood cell transfusion and/or iron infusion dependence, as defined by a hematologic support score (HSS) of ≥3 in the 3 months prior to consent. HSS is calculated by dividing the total milligrams of elemental iron infused by 250 and adding to this the number of red cell units transfused.
• ECOG performance status ≤2 (see Appendix B).
• Participants must have adequate organ and marrow function as defined below:
• leukocytes ≥2,000/mcL
• absolute neutrophil count ≥1,000/mcL
• platelets ≥50,000/mcL
• AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN\*
• creatinine ≤ 2.5 mg/dL OR
• glomerular filtration rate (GFR) ≥45 mL/min/1.73 m2 \*Except AST and/or ALT elevation related to HHT-associated hemolytic anemia or liver AVMs, in the opinion of the investigator. Bilirubin thresholds are not included as mild chronic hyperbilirubinemia is common in HHT, likely related to subclinical hemolysis in AVMs. Patients with clinically advanced liver disease should be excluded from participation.
• The effects of bevacizumab on the developing human fetus are unknown. For this reason and because anti-angiogenic agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women should additionally use adequate contraception for the 6 months after discontinuation of bevacizumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of bevacizumab administration.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Participants who have received intranasal or systemic bevacizumab, systemic ramucirumab, or systemic ziv-aflibercept in the 6 weeks prior to consent.
• Participants who have received oral anti-angiogenic agents, including pazopanib, axitinib, sorafenib, thalidomide, lenalidomide, or pomalidomide in the 6 weeks prior to consent.
• Participants receiving oral tranexamic acid or epsilon-aminocaproic acid unless they are on a stable dose for at least 2 weeks prior to consent to be continued at that same dose over the entire duration of the study.
• Participants receiving erythropoiesis-stimulating agents unless they are on a stable dose for at least 4 weeks prior to consent to be continued at that same dose over the entire duration of the study.
• Participants receiving oral iron preparations must discontinue these preparations prior to the initiation of the study (Day 1). Multivitamins or other pharmaceuticals containing iron are allowed if the daily dose of elemental iron does not exceed 25 mg per day.
• Participants who are receiving any other investigational agents.
• History of allergic reactions to bevacizumab.
• Participants with uncontrolled intercurrent illness, in the opinion of the investigator.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements, in the opinion of the investigator.
• Pregnant women are excluded from this study because bevacizumab is an anti-angiogenic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bevacizumab, breastfeeding should be discontinued if the mother is treated with bevacizumab. Pregnancy status will be assessed with a serum B-HCG pregnancy test. Women who are menopausal or perimenopausal will have follicle-stimulating hormone levels drawn to confirm menopausal status.
• Significant proteinuria, as defined by a urine protein of \>2.0 grams per day (on 24-hour urine protein collection or spot urine protein:creatinine ratio). 24-hour urine protein collection or spot urine protein:creatinine ratio is necessary during screening to quantify urine protein only in patients with screening urine dipstick/urinalysis demonstrates 3+ protein or higher.
• Poorly-controlled hypertension, as defined by a systolic blood pressure \>160 mm Hg or diastolic blood pressure \>100 mm Hg refractory to medical management.
• Serious or non-healing wound, ulcer or bone fracture.
• Recent hemoptysis, defined as hemoptysis of greater than or equal to one-half teaspoon of blood in the month prior to enrollment.
• Unwillingness to receive red blood cell transfusions and/or intravenous iron infusions according to the hematologic support protocol (HSP) while on study.

Sponsors & Collaborators

• Hanny Al-Samkari, MD: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Hanny Al-Samkari, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: May 28, 2020
• Study Start: November 23, 2020
• Primary Completion: March 2, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)