Haemophilic patients, with high responding inhibitor (>5 BU/ml), in whom previous ITI failed and who undergo the second line ITI protocol MedDRA version: 9.1 Level: PT Classification code 10016080
Conditions
Interventions
Pharmaceutical Form: Oral solution
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-
Pharmaceutical Form: Capsule, soft
Concentration unit: mg mil
Sponsors
STRUTTURA SEMPLICE GESTIONE-ORG.-FUNZ. HUB EMOFILIA
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1.patients with haemophilia A 2.any age 3.high responder inhibitors (peak inhibitor levels > 5 BU) 4.previous failure of ITI with any dosage of a FVIII concentrate, such as recombinant FVIII, monoclonally purified FVIII and/or FVIII/vWF concentrate 5.patients in whom the inhibitor was initially cleared, who then relapsed 6.ability to participate in the study and comply with the study-related activities 7.written informed consent Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.lack of informed consent 2.concomitant systemic treatment with drugs with immunosuppressive side effects for other diseases 3.hypersensitivity to cyclosporine or any of its components 4.renal failure 5.concomitant autoimmune disease or cancer 6.uncontrolled hypertension 7.HBV (HbsAg positive patients), HCV and HIV-positive patients, tuberculosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To assess the clinical response to a rescue ITI protocol associated with immunomodulation in patients not responding to standard ITI 2.To assess maintenance of immune tolerance after immunomodulation and ITI withdrawal 3.To assess the immunological mechanisms involved in induction and maintenance of tolerance to FVIII;Secondary Objective: - To identify clinical and immunological predictors of successful treatment. - To assess the time of clinical response. - To assess the patients compliance to the treatment. - To monitor the effects of achieving tolerance on quality of life. - Evaluation of the risk/benefit ratio of immunomodulation;Primary end point(s): I. Complete success: absence of the inhibitor, FVIII recovery ≥66% and half-life ≥6 hours, measured after a 72-hour treatment-free wash-out period. II. Partial response: a reduction in inhibitor titre to 5 BU/ml over a period of 6 months of on-demand treatment or 12 months of prophylaxis. III. Failure: failure to fulfil the criteria for complete or partial response, or a less than 20% reduction in inhibitor titre, relative to the peak inhibitor titre on ITI, over any 6-month period after the first 3 months of treatment. IV. Maintenance of immune tolerance: absence of relapse, assayed up to 12 months after the achievement of tolerance and at suspension of immunomodulatory therapy | — |
Countries
Italy
Outcome results
None listed