Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children (NEPHROVIR3)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: First Manifestation of Steroid Sensitive Nephrotic Syndrome

Treatments: Drug: Levamisole Hydrochloride; Other: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02818738

P150904

Details and patient eligibility

About

Idiopathic Nephrotic Syndrome is sensitive to steroid in 90% of children. However, most patients relapse and become steroid-dependant, with a long lasting relapsing course. The aim of this study is to assess the efficiency of a 6-months levamisole course, given early after first remission, on maintaining a relapse-free course at 12 months.

Full description

Introduction (INS) is likely a primal immune disorder. Initial treatment relies on steroid therapy. NS is sensitive to steroid in more than 90% of cases, with an excellent renal prognosis. Nevertheless, 80% of patients with steroid sensitive NS do relapse, 60% within the first year. 2/3 of them will experience steroid dependency, with a long lasting relapsing course. These patients require further immunosuppressive drugs as steroid sparing agents, such as mycophenolate, cyclophosphamide, calcineurin inhibitors or rituximab. Morbidity is high and related both to the duration of the disease, sometimes until adulthood, and to treatments side effects.

Levamisole is an immunomodulator that has been used for more than thirty years in the treatment of steroid-dependent or frequently relapsing NS. Its major advantages are its immunomodulatory action and lower and reversible toxicity.

Exact physiopathology of both INS and levamisole action remain unknown. Nevertheless, we make the hypothesis that very early treatment with levamisole may enhance its efficiency and modify the disease's course.

This is the first trial to assess the efficiency of levamisole in increasing duration of remission after the first manifestation of INS.

Design :

• A multicenter, double-blind, placebo-controlled, randomised clinical trial.
• 38 centers participate to the recruitment : 3 Pediatric Nephrology units and 35 General Pediatric units.
• 20 centers participate to the randomized phase.

Sample size :

156 patients, 78 in each group

Treatment groups :

1. Levamisole Hydrochloride Dosage : 5, 10, 25 et 50mg. Dosage form : oral tablets Posology : 2.5 mg/kg on alternate days maximum 150mg. Treatment duration : 6 months
2. placebo : matching verum

Assessment :

Study visits at inclusion, M1 (randomisation), M3, M6, M9, M12. Supplementary visit if relapse occurs.

Statistical procedure Analysis of efficiency will be performed on intention to treat population. Analysis of tolerance will be performed on randomized patients who have received at least one dose of treatment.

No intermediary analysis is planned.

Enrollment: 86 patients

Sex: All

Ages: 24 months to 16 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 24 months < age < 16 years
• Diagnosis of first manifestation of INS defined by:
• hypoalbuminemia < 25g/l, proteinuria > 0.20 g/mmol of urinary creatinine
• normal C3 fraction of complement
• Use of mechanical contraception for patients of reproductive age throughout the research period
• Beneficiary of a social protection scheme (except AME)
• Written informed consent from one of both parents
• Ability to realise follow-up in full

Exclusion criteria

• Anteriority of INS
• Pregnancy, breast feeding or planned pregnancy during the study
• Malignant pathology (antecedent or ongoing), diabetes, liver disease
• Hypersensitivity to levamisole or its excipients (lactose)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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86 participants in 2 patient groups, including a placebo group

Levamisole Hydrochloride

Experimental group

Description:

Dosage : 5, 10, 25 et 50mg. Dosage form : oral tablets, coated and non dividable for taste-masking Posology : 2.5 mg/kg on alternate days maximum 150mg. Treatment duration : 6 months

Treatment:

Drug: Levamisole Hydrochloride

Placebo

Placebo Comparator group

Description:

matching verum

Treatment:

Other: Placebo