Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)

NCT02106520 | Terminated Phase 2 DMC

• 1 other identifier: 2013.827
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare (\~ 1/6000) but ubiquitous genetic disease. It is associated with abnormal angiogenesis and autosomal dominant inheritance, leading to telangiectasias and arteriovenous fistulae. More than 95% of patients are concerned by epistaxis (nosebleeds). These events are spontaneous, repeated, irregular, both diurnal and nocturnal, a source of anemia, disabling and very socially embarrassing. Anti-angiogenic treatments, including bevacizumab, are a new therapeutic option in HHT. The aim of this study is to evaluate 3 months after the end of the treatment the efficacy on the duration of the nosebleeds with 3 different doses (25, 50 and 75 mg) of bevacizumab administered as a nasal spray in a repeated manner (3 administrations) in patients with Hereditary Hemorrhagic Telangiectasia complicated by nosebleeds. This randomized, double-blind, placebo-controlled, seamless phase II/III study is to be carried out on 4 groups of 20 patients for first step and 2 groups of 20 to 40 patients for second step

Conditions

Hereditary Hemorrhagic Telangiectasia; Epistaxis

Keywords

Epistaxis; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• mean duration of epistaxis

  To evaluate 3 months after the end of the treatment the efficacy on the duration of the nosebleeds with 3 different doses (25, 50 and 75 mg) of bevacizumab administered as a nasal spray in a repeated manner (3 administrations).

  3 months after treatment

Secondary Outcomes (7)

• adverse events

  before and 6 months after treatment

• mean monthly epistaxis duration

  6 months after the end of the treatment

• frequency and duration of epistaxis

  3 months and 6 months after the end of the treatment

• Quality of life

  3 months and 6 months aftert the end of the treatment

• Number of red blood cells transfusion

  3 months and 6 months after the end of the treatment

Study Arms (4)

Bevacizumab 25mg

EXPERIMENTAL

Three administrations of 25 mg of Bevacizumab spaced of 14 days

Drug: Bevacizumab

Bevacizumab 50mg

EXPERIMENTAL

Three administrations of 50 mg of Bevacizumab spaced of 14 days

Drug: Bevacizumab

Bevacizumab 75mg

EXPERIMENTAL

Three administrations of 75 mg of Bevacizumab spaced of 14 days

Drug: Bevacizumab

Placebo

PLACEBO COMPARATOR

Three administrations of placebo spaced of 14 days

Drug: placebo

Interventions

Bevacizumab DRUG

Also known as: Three administrations of Bevacizumab spaced of 14 days

Bevacizumab 25mg; Bevacizumab 50mg; Bevacizumab 75mg

placebo DRUG

Also known as: Three administrations of placebo spaced of 14 days

Placebo

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Patients who have given their free informed and signed consent.
• Patients affiliated to a social security scheme or similar.
• Patients monitored for clinically confirmed HHT (presence of at least 3 Curaçao criteria) and/or confirmed by molecular biology.

You may not qualify if:

• Women who are pregnant or likely to become so in the course of the study.
• Patients not affiliated to a social security scheme.
• Patients who are protected adults under the terms of the law (French Public Health Code).
• Refusal to consent.
• Patients for whom the diagnosis of HHT has not been confirmed clinically and/or by molecular biology.
• Patients with an on-going infectious condition.
• Known hypersensitivity to the active ingredient or one of the excipients.
• Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other human or humanized recombinant antibodies.
• Patients who have incompletely filled in the nosebleed grids in the 3 months preceding the treatment.
• Patients who do not present with nosebleeds with a monthly average duration over the 3 months preceding the treatment of more than 20 minutes ((duration M1 + duration M2 + duration M3) / 3). Remark: only the 3 months strictly preceding the treatment will be taken into account, even if the grids have been completed over a longer period.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Louis Pradel

Bron, 69677, France

Location

Related Publications (1)

• Dupuis-Girod S, Ambrun A, Decullier E, Fargeton AE, Roux A, Breant V, Colombet B, Riviere S, Cartier C, Lacombe P, Chinet T, Blivet S, Blondel JH, Gilbert-Dussardier B, Dufour X, Michel J, Harle JR, Dessi P, Faure F. Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia: A Randomized Clinical Trial. JAMA. 2016 Sep 6;316(9):934-42. doi: 10.1001/jama.2016.11387.

  PMID: 27599328 DERIVED

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic; Epistaxis

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; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Sophie DUPUIS-GIROD, MD

  Service de génétique, Hôpital Louis Pradel, Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2014
• First Posted: April 8, 2014
• Study Start: April 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: September 1, 2015
• Last Updated: November 20, 2015

Record last verified: 2015-11

Locations

FR (1)