Prevention of the return of nephrotic syndrom in children by adding levamisole to the prednison treatment

• Register: EUCTR
• Last refreshed on: 26 March 2018
• Main ID: EUCTR2017-001025-41-NL
• Date of registration: 06/12/2017
• Prospective Registration: Yes
• Primary sponsor: Academic Medical Center
• Public title: Prevention of the return of nephrotic syndrom in children by adding levamisole to the prednison treatment
• Scientific title: Prevention of relapse with Levamisole as adjuvant therapy to corticosteroids in children with first episode of idiopathic nephrotic syndrome - LEARNS
• Date of first enrolment: 08/03/2018
• Target sample size: 92
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001025-41
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Learns Clinical Trial Team
• Affiliation: Academic Medical Center

• Name: Learns Clinical Trial Team
• Affiliation: Academic Medical Center

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria for biobanking/immunomics:
- Children with first episode of INS aged between 2 and 16 years.
- INS definition: Hypoalbuminaemia (albumin <25 g/L); Proteinuria (>200 mg/mmol creatinine); Complement C3 within normal range.
- Written informed consent

Inclusion criteria for RCT
- Steroid-sensitive INS (Remission after 4 weeks of corticosteroid treatment)
- Weight >9 kg
- Ability to swallow a (placebo) tablet of 5 mg (successful swallowing test in children <6 years)
- Negative pregnancy test in girls that are of childbearing potential
- Absence of contraindication for levamisole use: neutropenia <1500/mmP3
- Written informed consent
- Ability to comply with study protocol
Are the trial subjects under 18? yes
Number of subjects for this age range: 92
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion criteria for biobanking/immunomics:
- Previous episodes of INS

Exclusion criteria for RCT:
- Steroid-resistant INS (persistent proteinuria at 4 weeks after start steroid treatment).
- Previous or current malignancy, diabetes mellitus, current liver disease, or convulsions.
- Hypersensitivity to levamisole or one of its substances (lactose)


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

Health Condition(s) or Problem(s) studied

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

steroid sensitive idiopathic nephrotic syndrome
MedDRA version: 20.1 Level: PT Classification code 10029164 Term: Nephrotic syndrome System Organ Class: 10038359 - Renal and urinary disorders

Intervention(s)

Product Name: Levamisole 5 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LEVAMISOLE HYDROCHLORIDE
CAS Number: 16595-80-5
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Levamisole 10 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LEVAMISOLE HYDROCHLORIDE
CAS Number: 16595-80-5
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Levamisole 25 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LEVAMISOLE HYDROCHLORIDE
CAS Number: 16595-80-5
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Levamisole 50 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: LEVAMISOLE HYDROCHLORIDE
CAS Number: 16595-80-5
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To investigate the effect of additional levamisole in comparison with placebo from 4 weeks to 6 months after the start of the first episode of steroid-sensitive INS in children (age 2 – 16 years) on the occurrence of relapses within 12 months.

Primary end point(s): The occurrence of relapses within 12 months after first presentation. A relapse is defined as the recurrence of proteinuria (3+ urine dipstick or proteinuria> 200 mg/mmol creatinine) for 3 consecutive days

Secondary Objective: - To investigate HRQoL at different stages of treatment
- To identify medical and personal factors related to HRQoL, psychosocial adaptation and parental distress.
- To investigate the saliva/plasma concentration ratio of prednisolone and levamisole.
- To determine PK/PD of levamisole and prednisolone.
- To investigate the applicability of saliva for determination of the prednisolone and levamisole plasma concentrations
- To establish the functional immune disorders in INS using full-blood stimulation before and after start of treatment and upon relapse.
- To establish the phenotype changes and differences of genotype of the immune system.
- To establish the stratification of patients at risk for recurrent disease and identify immunological pathways.
- To provide insight in the mechanism of action of levamisole in the prevention of relapses
- To investigate the consequences of INS in terms of days of missing school, outpatient visits, hospital admission and therapy costs

Timepoint(s) of evaluation of this end point: 12 months after first presentation with Idiopatic Nephrotic syndrome

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary endpoints are analysed as time to first occurance and amount of occurrences during the duration of the study

Secondary end point(s): - Time to first relapse;
- Relapse rate (number of relapses per person year) over 2-year period;
- Cumulative steroid dosage up to 2 years;
- Occurrence of adverse events and treatment discontinuation;
- Proportion of frequent relapsers or steroid dependency over 2-year period;
- Toxicity of levamisole:
- Proportion of patients with elevated ASAT-/ALAT-levels (>3 times upper limit of normal), neutropenia (<1500/mm3) or positive ANCA.
- Toxicity of corticosteroids:
- Differences in BMI, blood pressure, height, weight, serum glucose between groups.
- Proportion of patients with overweight (BMI >25 kg/m2, hypertension (p>90), and hyperglycemia.
- Days of school missing, outpatient visits and hospitalization days (macro-economic analysis);
- Number of treatment interruptions.

Secondary ID(s)

NL61906.018.17

Source(s) of Monetary Support

ACE Pharmaceuticals

Dutch Kidney Foundation