A single-center randomized double-blind placebo-controlled trial “Treatment of Systemic Sclerosis with Rituximab: evaluation of the effectiveness of B-cell depletion therapy”

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2012-004955-35-IT
• Date of registration: 30/05/2013
• Prospective Registration: Yes
• Primary sponsor: POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI
• Public title: A single-center randomized double-blind placebo-controlled trial “Treatment of Systemic Sclerosis with Rituximab: evaluation of the effectiveness of B-cell depletion therapy”
• Scientific title: A single-center randomized double-blind placebo-controlled trial “Treatment of Systemic Sclerosis with Rituximab: evaluation of the effectiveness of B-cell depletion therapy”
• Date of first enrolment: 29/07/2013
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004955-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Italy

Contacts

• Name: DIVISIONE DI REUMATOLOGIA
• Affiliation: POLICLINICO GEMELLI- COMPLESSO INTEGRATO COLUMBUS

• Name: DIVISIONE DI REUMATOLOGIA
• Affiliation: POLICLINICO GEMELLI- COMPLESSO INTEGRATO COLUMBUS

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with age between 18 and 70 years;
2. SSc diagnosis with diffuse cutaneous involvement, accordingly to ACR and Le-Roy criteria;
3. Worsening of skin involvement, evaluated with Rodnan skin score, higher than 10% in the last 2-3 months;
4. Capacity to sign the informed consent;
5. Previous treatment with intravenous pulse 6-metilprednisolone and oral Cyclophosphamide (at least 6 grams);
Enrolled patients should ensure not to intend to get pregnant during the treatment and for 6 months after the last dose of Rituximab and Cyclophoasphamide

Are the trial subjects under 18? no
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 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
1. Severe lung and heart involvement, with dyspnea and signs or symptoms of heart or lung failure (Oxigen saturation lower than 60%, FVC<50%, FE<40%, DLCO<40%)
2. Patients with acute and chronic infections;
3. Hystory of immunodeficiency, tubercolosis or cancer;
4. Pregnancy and feeding;
Moderate or severe renal failure (creatinine clearance <30 ml/min)



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

Health Condition(s) or Problem(s) studied

SYSTEMIC SCLEROSIS
MedDRA version: 16.0 Level: PT Classification code 10042953 Term: Systemic sclerosis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: Mabthera
Pharmaceutical Form: Powder for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 3/6/12/24 MONTHS

Primary end point(s): • Rituximab efficacy on skin involvement through Rodnan skin score. We will consider clinically relevant a decrease of skin score higher than 30% compared to initial skin score
• Rituximab efficacy on lung involvement. We will consider clinically relevant an increase higher than 10% for FVC and TLC and/or higher than 15% for DLCO, and/or a decrease of extension of ground glass and honey-combing scores higher of 2 points on lung HRCT
• Safety and tolerability of the drug
Efficacy on arthritis manifestations evaluated with DAS (disease activity score), number of swollen and tender joints, analogic scale for pain.

Main Objective: Safety and tolerability of Rituximab on skin and lung fibrosis in patients with Systemic Sclerosis previously treated with intravenous pulse 6-metilprednisolone and Cyclophosphamide

Secondary Objective: NA

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 3/6/12/24 MONTHS

Secondary end point(s): • Activity and severity index for scleroderma patients
• Efficacy on patient disability through “health global assessment” and “Health Assessment Questionnarie”.
• Changes of capillaroscopic CSURI score,
• Fibrotic and inflammatory cytokines levels in serum and plasma only in patients that accept this optional part of the study
Entity of cellular infiltrate on skin biopsies before and after therapy ( 6 and 24 month) only in patients that accept this optional part of the study

Secondary ID(s)

1883/12

Source(s) of Monetary Support

UNIVERSITA' CATTOLICA