Efficacy of thalidomide in the treatment of heavy and frequent nose bleeding in patients affected by hereditary hemorrhagic telangiectasia

• Register: EUCTR
• Last refreshed on: 19 February 2018
• Main ID: EUCTR2011-004096-36-IT
• Date of registration: 19/03/2012
• Prospective Registration: No
• Primary sponsor: OSPEDALE POLICLINICO S. MATTEO
• Public title: Efficacy of thalidomide in the treatment of heavy and frequent nose bleeding in patients affected by hereditary hemorrhagic telangiectasia
• Scientific title: Efficacy of thalidomide in the treatment of severe recurrent epistaxis in hereditary hemorrhagic telangiectasia (HHT)
• Date of first enrolment: 11/10/2011
• Target sample size: 31
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004096-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy

Contacts

• Name: Struttura di Medicina Generale III
• Affiliation: Fondazione IRCCS Policlinico San Matteo

• Name: Struttura di Medicina Generale III
• Affiliation: Fondazione IRCCS Policlinico San Matteo

Key inclusion & exclusion criteria

Inclusion criteria:
- Diagnosis of HHT, according to the diagnostic criteria world-wide recognized (Curacao criteria, with severe recurrent epistaxis (grade 2-3) and refractory to mini-invasive surgical procedures. - Age > 18 years - Ability of signing written informed consent - Women of childbearing potential: declared intention not to start a pregnancy throughout the study and for four weeks following the date of the last dose of thalidomide, negative serum pregnancy test obtained within 48 hours prior to the first dose of Thalidomide, declared intention to undergo pregnancy tests periodically while on the study medication - Males with female partner of childbearing potential: declared intention not to father throughout the study and for one week following the date of the last dose of thalidomide - Estimated life expectancy must be greater than 10 months
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 11
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
- Pregnant or lactating women, or potentially fertile (both males and females) who have not agreed to avoid pregnancy during the trial period and for four weeks (females) or one week (males) following the date of the last dose of thalidomide - Neurological diseases - Psychiatric illness that would prevent granting of informed consent - Active cardiovascular disease - High risk for thromboembolic events - Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption since thalidomide capsules contain lactose


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Severe recurrent epistaxis in hereditary hemorrhagic telangiectasia
MedDRA version: 14.1 Level: LLT Classification code 10038554 Term: Rendu-Osler-Weber syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Intervention(s)

Trade Name: THALIDOMIDE CELGENE*28CPS 50MG
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: THALIDOMIDE
CAS Number: 50-35-1
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable

Primary end point(s): Percentage of patients showing a decrease in the frequency, intensity and duration of epistaxis and in the blood transfusion requirement.

Secondary Objective: - Safety and Tolerability - To ascertain whether thalidomide reduces telangiectasias in nasal mucosa - To assess specific biological and clinical parameters predictable for patients response and side effects profile.

Main Objective: To assess the clinical effects of thalidomide therapy on the severity of epistaxis in subjects with HHT who are refractory to standard therapies.

Secondary Outcome(s)

Secondary end point(s): - Size and number of telangiectasias evaluated by endoscopy of nasal mucosa at baseline and at least every 8 weeks thereafter - Requirement of blood transfusions - Minimum dose of the drug that reduces bleeding - Time to Response - Time to relapse after the end of treatment - Safety and tolerability of thalidomide in HHT - Correlations between the mutations that are responsible for HHT and response to treatment - Correlations between polymorphisms of CYP2C19 and response to treatment - Correlations between polymorphisms of CYP2C19 and side effects profile

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

THALI-HHT

Source(s) of Monetary Support

Celgene S.r.L.