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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

29 Nov 2024 → ongoing

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Nederlandse Nierstichting

External identifiers

EU CT number

2024-517467-23-00

EudraCT number

2017-001025-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Safety, Pharmacodynamic

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.

Secondary objectives 10

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

Conditions and MedDRA coding

steroid sensitive idiopathic nephrotic syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Steroid-sensitive INS (Remission after 4 weeks of corticosteroid treatment)
2. Weight >9 kg
3. Ability to swallow a (placebo) tablet of 5 mg (successful swallowing test in children <6 years)
4. Negative pregnancy test in girls that are of childbearing potential
5. Absence of contraindication for levamisole use: neutropenia <1500/mmP3
6. Written informed consent
7. Ability to comply with study protocol

Exclusion criteria 3

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 9

1. Time to first relapse
2. Relapse rate (number of relapses per person year) over 2-year period
3. Cumulative steroid dosage up to 2 years
4. Occurrence of adverse events and treatment discontinuation
5. Proportion of frequent relapsers or steroid dependency over 2-year period
6. Toxicity of levamisole: Proportion of patients with elevated ASAT- /ALAT-levels (>3 times upper limit of normal), neutropenia (<1500/mm3) or positive ANCA.
7. 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
8. Days of school missing, outpatient visits and hospitalization days (macro-economic analysis)
9. Number of treatment interruptions

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Dr. A.H. Bouts

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Dr. A.H. Bouts

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications