Ranibizumab for the Management of Recurrent Nosebleeds in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)

Sponsor

University of California, San Diego (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01406639

Collaborator

Genentech, Inc. (Industry)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

Brief Summary

This study is for patients with recurrent epistaxis (nosebleeds) as a result of Hereditary Hemorrhagic Telangiectasia (HHT). The aim is to determine if ranibizumab, topically applied will diminish epistaxis in patients with HHT as measured by the HHT Epistaxis Severity Score (ESS), hematocrit, and hemoglobin and serum ferritin levels.

Condition or Disease	Intervention/Treatment	Phase
Hereditary Hemorrhagic Telangiectasia (HHT) Nosebleeds	Drug: Ranibizumab	Phase 1

Detailed Description

This is an open-label, Phase I study of intranasal administered ranibizumab in subjects with HHT. Plans are to recruit patients with HHT from the UCSD Nasal Dysfunction Clinic.

Those who come for evaluation and are deemed appropriate for topical ranibizumab without laser will be recruited for this study. Ten (10) consented, enrolled subjects will receive a pulsatile nasal irrigator to clean their nose twice daily. They will complete the initial ESS and have a blood test for Hct, Hgb, serum ferritin, liver function tests, renal function tests and if of child-bearing age, a urine pregnancy test. They will return 1 week later and will then receive intranasal sprays of ranibizumab administered once per week during clinic. Patients will be treated with a total of 4 applications of ranibizumab in a fine mist spray. This will be done with 2 mgs in 0.2cc; 0.1cc sprayed into each nostril a day; therefore 8 mgs will require 4 days of application. If, following the first treatments, they experience recurrent bleeding (equal to or less than a 75% reduction in their ESS number as compared to pre treatment), they will be offered the opportunity to be prescribed a second administration, to be completed in the same way (4 applications of 4 mg in 0.4 cc with 0.2cc per nostril).

At the completion of the treatment, subjects will be observed monthly for examination and ESS until 6 months from the first treatment. At 3 and 6 months laboratory tests will be performed.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Ranibizumab for the Management of Recurrent Epistaxis in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)

Study Start Date :

Jul 1, 2011

Actual Primary Completion Date :

May 1, 2012

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranibizumab Patients treated with topical ranibizumab.	Drug: Ranibizumab Patients will be treated with a total of 4 applications of ranibizumab in a fine mist spray. This will be done with 2 mgs in 0.2cc; 0.1cc sprayed into each nostril a day; therefore 8 mgs will require 4 days of application. If, following the first treatments, they experience recurrent bleeding (equal to or less than a 75% reduction in their ESS number as compared to pre treatment), they will be offered the opportunity to be prescribed a second administration, to be completed in the same way (4 applications of 4 mg in 0.4 cc with 0.2cc per nostril). Other Names: Lucentis

Arm

Intervention/Treatment

Experimental: Ranibizumab

Patients treated with topical ranibizumab.

Drug: Ranibizumab

Patients will be treated with a total of 4 applications of ranibizumab in a fine mist spray. This will be done with 2 mgs in 0.2cc; 0.1cc sprayed into each nostril a day; therefore 8 mgs will require 4 days of application. If, following the first treatments, they experience recurrent bleeding (equal to or less than a 75% reduction in their ESS number as compared to pre treatment), they will be offered the opportunity to be prescribed a second administration, to be completed in the same way (4 applications of 4 mg in 0.4 cc with 0.2cc per nostril).

Other Names:

Lucentis

Outcome Measures

Primary Outcome Measures

Epistaxis as measured by the HHT Epistaxis Severity Score (ESS), hematocrit, and hemoglobin and serum feritin levels. [Monthly until 6 months from the first treatment.]
Epistaxis will be evaluated on a monthly basis by the HHT Epistaxis Severity Score (ESS), hematocrit, and hemoglobin and serum ferritin levels. This will continue through 6 months after the first treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Subjects will be eligible if the following criteria are met:

Ability to provide written informed consent and comply with study assessments for the full duration of the study
Age > 18 years
Diagnosed with HHT
Deemed appropriate for topical Ranibizumab without laser, as determined by severity. For the Ranibizumab to be effective, the spray needs to reach the nasal mucosa. Patients will be instructed in nasal irrigation and will only be treated if they can keep their noses clean.
Severe patients will presumably not achieve this goal, so subjects will be patients with moderate disease as defined by the epistaxis severity score sheet (Appendix B)

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from this study:

Coagulopathy
Pregnancy (positive pregnancy test) or lactation
Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch
Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
Participation in another simultaneous medical investigation or trial
Patients who have had bevacizumab therapy, injection, or spray
Patients with a known reaction based on macular degeneration treatment
Patients having received VEGF inhibitors in the last 2 years for the treatment of any ophthalmologic disease