First Manifestation of Steroid Sensitive Nephrotic SyndromePhase 3NEPHROVIR3NCT02818738
Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children
A Phase 3 study testing Levamisole Hydrochloride in people with First Manifestation of Steroid Sensitive Nephrotic Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 24 months to 16 years
- Conditions the study is for
- First Manifestation of Steroid Sensitive Nephrotic Syndrome
- What is being tested?
- Levamisole Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 1 siteFrance
- Study dates
- 6 Sep 2017to 11 Feb 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 months to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter, Randomised, Double-blind Placebo-controlled Trial Assessing the Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children.
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.
Read the detailed 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 :
- 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
- 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.
- Being tested
- Levamisole Hydrochloride, Placebo
- Keywords
- Idiopathic nephrotic syndrome, Steroid sensitive nephrotic syndrome, Levamisole, Prednisone, Children
- Medical subject headings
- Nephrosis, Lipoid, Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levamisole HydrochlorideDrug
Dosage : 5, 10, 25 et 50 mg. 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
PlaceboOther
matching verum
| Study group | Role | What they receive |
|---|---|---|
| Levamisole Hydrochloride | Experimental | 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 Receives: Drug: Levamisole Hydrochloride |
| Placebo | Placebo comparator | matching verum Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients still in remission at 12 months after first flare of INS.
number of patients who did not relapse compared to the number of patients who had relapsed after first flare of INS.
Measured: 12 months
Secondary outcomes (3)
Compare within levamisole and placebo groups the duration of remission.
number of days between the first flare and first relapse or up to the corticodependence level in the event of relapse in the course of decreasing corticosteroid therapy.
Measured: first relapse
Compare within levamisole and placebo groups the frequency and level of steroid dependency
Proportion of corticodependent patients and level of steroid dependency
Measured: 12 months
Compare within levamisole and placebo groups the treatment tolerance
Frequency of adverse events apparition and frequency of discontinuation of treatment secondary at a adverse event.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2016 (estimated)
- Study start6 Sep 2017
- Primary completion7 Feb 2021
- Study completion11 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for First Manifestation of Steroid Sensitive Nephrotic SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Claire DOSSIER, MD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02818738
- Sponsor's protocol ID
- P150904
- Acronym
- NEPHROVIR3
- Status last verified
- May 2022
- First submitted
- 8 Jun 2016
- Last updated
- 8 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.
PubMed 39513526
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomised, Double-blind Placebo-controlled Trial Assessing the Efficiency of Levamisole for Maintaining Remission After the First Flare of Steroid Sensitive Nephrotic Syndrome in Children.
- ClinicalTrials.gov ID
- NCT02818738
- Acronym / sponsor ID
- NEPHROVIR3 / P150904
- Keywords
- Idiopathic nephrotic syndrome, Steroid sensitive nephrotic syndrome, Levamisole, Prednisone, Children
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 6 Sep 2017 (actual)
- Primary completion
- 7 Feb 2021 (actual)
- Study completion
- 11 Feb 2021 (actual)
- First posted
- 30 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 :
- 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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levamisole Hydrochloride | Experimental | Drug: Levamisole HydrochlorideDosage : 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 |
| Placebo | Placebo comparator | Other: Placebomatching verum |
Who may qualify
- Ages
- 24 months to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (4 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Levamisole HydrochlorideDosage : 5, 10, 25 et 50 mg. 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 | Drug | Levamisole Hydrochloride |
| Placebomatching verum | Other | Placebo |
Primary outcome
Percentage of patients still in remission at 12 months after first flare of INS.
Time frame: 12 months
number of patients who did not relapse compared to the number of patients who had relapsed after first flare of INS.
3 secondary outcomes
Compare within levamisole and placebo groups the duration of remission.
Time frame: first relapse
Compare within levamisole and placebo groups the frequency and level of steroid dependency
Time frame: 12 months
Compare within levamisole and placebo groups the treatment tolerance
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2022.
- Derived from this study: PubMed 39513526Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claire DOSSIER, MD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Levamisole Hydrochloride in people with First Manifestation of Steroid Sensitive Nephrotic Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients still in remission at 12 months after first flare of INS. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02818738, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2022.