definite or probable ALS MedDRA version: 20.0 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: RAPAMUNE - 1 MG 100 COMPRESSE RIVESTITE IN BLISTER USO ORALE
Product Name: Rapamune
Pharmaceutical Form: Coated tablet
Sponsors
AZIENDA OSPEDALIERO-UNIVERSITARIA POLICLINICO DI MODENA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient diagnosed with a laboratory supported , clinically “probable” or “definite” amyotrophic lateral sclerosis according to the Revised El Escorial criteria (Brooks, 2000) - Familial or sporadic ALS - Female or male patients aged between 18 and 75 years old - Disease duration from symptoms onset no longer than 18 months at the screening visit - Patient treated with a stable dose of Riluzole (100 mg/day) for at least 30 days prior to screening - Patients with a weight > 50 kg and a BMI =18 - Patient with a FVC = 70 % predicted normal value for gender, height, and age at the screening visit - Patient able and willing to comply with study procedures as per protocol - Patient able to understand, and capable of providing informed consent at screening visit prior to any protocol-specific procedures - Use of effective contraception both for males and females Are the trial subjects under 18? no Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: - Prior use of Sirolimus - Prior allergy/sensitivity to Sirolimus or macrolides - Any medical disorder that would make immunosuppression contraindicated, including but not limited to, acute infections requiring antibiotics, patients with known diagnosis of HIV, TBC, hepatitis B or C infection or history of malignancy - Severe comorbidities (heart, renal, liver failure), autoimmune diseases or any type of interstitial lung disease - White blood cells<4,000/mm³, platelets count<100,000/mm³, hematocrit<30% - Patient who underwent non invasive ventilation, tracheotomy and /or gastrostomy - Women who are pregnant or breastfeeding - Participation in pharmacological studies within the last 30 days before screening - Patients with known SOD1 mutation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether Rapamycin administration increases Tregs number in treated patients compared to control arm;Secondary Objective: To assess safety and tolerability of Rapamycin in ALS patients; to assess the minimum dosage to have RAPAMYCIN in CSF; to assess changes in immunological (activation and homing of T,B,NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); to assess clinical activity (ALSFRS-R, survival, FVC) and effect on quality of life (ALSAQ40). To assess if and at what dosage Rapamycin passes through blood brain barrier (BBB).;Primary end point(s): Proportion of patients exhibiting a positive response (considered as increase in Treg of at least 30%), comparing baseline and treatment end (WEEK 18) between Rapamycin and placebo arm, using mAbs anti-CD3,-4,-25,-127,-FoxP3 plus activation (HLA-DR,CD38) and homing (CXCR3) markers and flow cytometry (FCM);Timepoint(s) of evaluation of this end point: Week 18 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Measuring Rapamycin level in CSF 2. Quantifying the phosphorylation of the S6 ribosomal protein (S6RP) between Rapamycin arm and placebo arm 3. Measure changes in different biomarkers (creatinin e albumin, CK, vitamin D, neurofilament) between Rapamycin arm and placebo arm 4. Molecular analysis of the inflammasome system between Rapamycin arm and placebo arm 5. Amyotrophic Lateral Sclerosis functional rationg scale (ALSFRS) 6. Overall survival 7. Survival rate 8. Forced vital capacity (FVC) score;Timepoint(s) of evaluation of this end point: 1. Week 18 2. Baseline, week 8, 18 (treatment end), 30 and 54 3. Baseline, week 8, 18 (treatment end), 30 and 54 4. Baseline, week 8, 18 (treatment end), 30 and 54 5. Baseline, week 4, 8, 12, 18, 30, 42 e 54 6. From randomization to date of Death or tracheostomy 7. Week 18, 30, 42 and 54 8. Week 4, 8, 12, 18, 30, 42, 54 | — |
Countries
Italy
Contacts
Public ContactCoordinating Site
Nuovo Ospedale Civile S. Agostino Estense
Outcome results
None listed