Nephrotic SyndromePhase 2NCT05704400
Efficacy of Anti-CD20 Ab Associated With Anti-CD38 in the Childhood Multidrug Dependent and Resistant Nephrotic Syndrome
A Phase 2 study testing Rituximab Biosimilar ABP 798 and Daratumumab in people with Nephrotic Syndrome, run by Istituto Giannina Gaslini at 1 site in Italy.
Trial summary
Nephrotic syndrome is considered a disease caused by an interplay of immunological stimuli with adaptive immunity(CD80/CD40) as trigger and Treg in the mid between co-stimulatory molecules and effectors. Read more about this study
- Who is it for?
- Ages 3 to 24 years
- Conditions the study is for
- Nephrotic Syndrome
- What is being tested?
- Rituximab Biosimilar ABP 798 and Daratumumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 1 Mar 2023to 1 Mar 2025
- Phase
- Phase 2
- 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 3 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age between 3 and 24 years
- Multidrug dependent or resistant nephrotic syndrome for at least six months before enrolment. The need of at least 2 of the oral drugs listed below defines multidrug-dependence: prednisone at any doses, MMF 1200 mg m2 and CNI 0.1 mg day given in two doses. Dependence is defined by two consecutive relapses during double therapies or within 14 days of ceasing one of the three components of the therapeutic approach. Resistance is defined as lack of antiproteinuric effect of a double therapy based on steroid plusCNI or mofetilmycophenolate (MMF).Steroid resistance is defined by failure to achieve complete remission after 6 weeks with prednisone60 mg/m2.
- Post transplant recurrence of FSGS.
- Ability to provide consent and assent: parents'/guardian's written informed consent, and child's assent given before any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject any time without prejudice to his or her future medical care.
Who cannot join
- Positivity to autoimmunity tests (ANA, nDNA, ANCA)
- Reduction of C3 levels.
- eGFR<60/ml/min/1,73 m2 valuated according to revised Bedside Schwartz Formula for patients between 2 and 17 years and with CKD-EPI Creatinine 2009 Equation for 18 years old patients.
- Pregnancy
- Neoplasm
- Infections: previous or actual HBV (with HBeAb positivity) or HCV infection
- CD20 B lymphocytes count <2,5%
- Treatment with Rituximab or cyclophosphamide in the last 6 months
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
IRCCS G. Gaslini
Genova, 16148
GianMarco Ghiggeri, MD
About this study
Official title: Efficacy of Chimeric Monoclonal Anti-CD20 Antibodies (Rituximab Biosimilar) Associated With Monoclonal Anti-CD38 (Daratumumab) in the Treatment of Childhood Multidrug Dependent and Resistant (MDNS, MRNS) Nephrotic Syndrome
Nephrotic syndrome is considered a disease caused by an interplay of immunological stimuli with adaptive immunity(CD80/CD40) as trigger and Treg in the mid between co-stimulatory molecules and effectors. The positive effect of drugs blocking CD20 maturation in SDNS suggests a main role of these cells in regulating the system. Multidrug dependent, multidrug resistant nephrotic syndrome as well as post transplant FSGS recurrence patients can be considered difficult to treat patients and the association of two drugs, one targeting CD20 and a targeting plasmacells can be use in order to block the stimulatory cascade at more sites.
Read the detailed description
Nephrotic syndrome is considered a disease caused by an interplay of immunological stimuli with adaptive immunity(CD80/CD40) as trigger and Treg in the mid between co-stimulatory molecules and effectors. The positive effect of drugs blocking CD20 maturation in SDNS suggests a main role of these cells in regulating the system. One possible explanation of proteinuria resolution by anti-CD 20 in most but not all patients with SDNS/MDNS is that some CD20 cells may escape the inhibition and mature in some cases to plasmacells. On this basis, it seems reasonable to consider the association of two drugs, one targeting CD20 and one targeting plasmacells in order to block the stimulatory cascade at more sites. There are recent positive evidences from the association of 2 monoclonal antibodies that block maturation of CD20 at different steps. One study utilized the humanized anti-CD20 antibody obinutuzumab(single dose 1,000 mg 1.73m2) in combination with the anti-CD38 (plasmacells) monoclonal antibody daratumumab (1,000 mg 1.73m2)18 in patients who relapsed after conventional treatments with Prednisone, rituximab and CNI and developed dependence to the combination of more than 2 drugs (MDNS). A cohort of 14 patients treated with the above association were included in a retrospective analysis: all of them suspended oral drugs, 5 out of 14 presented recurrence of proteinuria after about 10 months, 9 out of 14 were in stable remission after 20 months. Therefore, the use of 2 monoclonal antibodies in low doses is potentially valuable considering the positive results and also taking in account the safety of the treatment. While it is not possible to discern the separate effects of obinutuzumab and daratumumab when given together, the preliminary positive results of their combination may open new ways in the treatment of nephrotic syndrome and supports the necessity of new studies in those patients who require more than one drug to maintain remission. The investigators hypothesize that rituximab in place of obinutuzumab (not available in Italy for the use in nephrotic syndrome) with daratumumab could produce the same positive effects in MDNS and MRNS.
The Dual 1 is a before-after clinical trial testing the superiority of rituximab plus daratumumab in maintaining drug free disease remission in patients with multi-drug dependent nephrotic syndrome.
- Conditions
- Nephrotic Syndrome
- Being tested
- Rituximab Biosimilar ABP 798, Daratumumab
- Medical subject headings
- Nephrotic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab Biosimilar ABP 798Drug
Rituximab IV: the dose is standard for pediatric nephrotic syndrome; for dosage between 100 and 250 mg rituximab will be diluted in 100 ml of normal saline and administered at 2 ml/h for the first 30'; 3 ml/h for the second 30'; 6 ml/h for the third 30'; 15 ml/h until the end. For dosage between 260 and 500 mg rituximab will be diluted in 250 ml of normal saline and administered at 6 ml/h for the first 30'; 9 ml/h for the second 30'; 18 ml/h for the third 30'; 36 ml/h until the end. For dosage between 510 and 1000 mg rituximab will be diluted in 500 ml of normal saline and administered at 9 ml/h for the first 30'; thereafter, the infusion rate can be doubled every 30 minutes up to a maximum of 72 ml/h.
DaratumumabDrug
Daratumumab vials 20 mg 1 ml will be collected to reach the desired dose of 16 mg /Kg, the dose is standard recommend to treat myeloma; diluted in 1000 ml of normal saline and infused at the constant speed of 50 ml/h. This will be reduced in case of cutaneous allergic reactions
| Study group | Role | What they receive |
|---|---|---|
| single arm | Experimental | Not described Receives: Drug: Rituximab Biosimilar ABP 798; Drug: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety- number of treatment-related adverse events
Primary: to test whether the combination of rituximab and daratumumab is safe and can achieve and maintain drug-free disease remission in patients with multi drug-dependent nephrotic syndrome within 12 months. The investigators will consider the number of participants with treatment-related adverse events as assessed by CTCAE v4.0 This outcome will not be compared but only studied following the intervention.
Measured: 12 months
Efficacy- number of months in remission
To test whether the combination of rituximab and daratumumab can achieve and maintain drug-free disease remission in patients with multi drug-dependent nephrotic syndrome within 12 months The investigators will compare the outcome of log-albuminuria following the infusion of the two drugs to the log-albuminuria before the infusion, when patients were maintained by the association of MMF and CNI (i.e. the drug recommended by Clinical Practice Guidelines-KDIGO as benchmark of the treatment).
Measured: 12 months
Secondary outcomes (1)
Prediction
To analyze B and T cell lymphocyte subsets pre and post-therapy with Rituximab/Daratumumab
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 Jan 2023
- Study start1 Mar 2023
- Primary completion1 Mar 2024 (estimated)
- Study completion1 Mar 2025 (estimated)
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 Nephrotic SyndromeStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase II Proof of concept, the Dual 1 is a before-after clinical trial testing the superiority of rituximab plus daratumumab in maintaining drug free disease remission in patients with multi-drug dependent nephrotic syndrome
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Giannina Gaslini
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gian Marco Ghiggeri MD, PhD, Istituto Giannina Gaslini
- Investigators
- Gianmarco Ghiggeri, MD, Principal investigator, IRCCS G. Gaslini
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05704400
- Sponsor's protocol ID
- DUAL1
- Status last verified
- Oct 2023
- First submitted
- 16 Dec 2022
- Last updated
- 31 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The completed study will be summarized in a final report that accurately and completely presents the study objectives, methods, results, limitations of the study, and interpretation of findings.
Publications
Angeletti A, Bruschi M, Kajana X, La Porta E, Spinelli S, Caridi G, Lugani F, Verrina EE, Ghiggeri GM. Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment. Front Immunol. 2023 Aug 29;14:1213203. doi: 10.3389/fimmu.2023.1213203. eCollection 2023.
PubMed 37705972
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Chimeric Monoclonal Anti-CD20 Antibodies (Rituximab Biosimilar) Associated With Monoclonal Anti-CD38 (Daratumumab) in the Treatment of Childhood Multidrug Dependent and Resistant (MDNS, MRNS) Nephrotic Syndrome
- ClinicalTrials.gov ID
- NCT05704400
- Acronym / sponsor ID
- DUAL1
- Conditions
- Nephrotic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Istituto Giannina GasliniUniversity, hospital or other
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 1 Mar 2024 (estimated)
- Study completion
- 1 Mar 2025 (estimated)
- First posted
- 30 Jan 2023 (actual)
- 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.
Nephrotic syndrome is considered a disease caused by an interplay of immunological stimuli with adaptive immunity(CD80/CD40) as trigger and Treg in the mid between co-stimulatory molecules and effectors. The positive effect of drugs blocking CD20 maturation in SDNS suggests a main role of these cells in regulating the system. Multidrug dependent, multidrug resistant nephrotic syndrome as well as post transplant FSGS recurrence patients can be considered difficult to treat patients and the association of two drugs, one targeting CD20 and a targeting plasmacells can be use in order to block the stimulatory cascade at more sites.
Detailed description
Nephrotic syndrome is considered a disease caused by an interplay of immunological stimuli with adaptive immunity(CD80/CD40) as trigger and Treg in the mid between co-stimulatory molecules and effectors. The positive effect of drugs blocking CD20 maturation in SDNS suggests a main role of these cells in regulating the system. One possible explanation of proteinuria resolution by anti-CD 20 in most but not all patients with SDNS/MDNS is that some CD20 cells may escape the inhibition and mature in some cases to plasmacells. On this basis, it seems reasonable to consider the association of two drugs, one targeting CD20 and one targeting plasmacells in order to block the stimulatory cascade at more sites. There are recent positive evidences from the association of 2 monoclonal antibodies that block maturation of CD20 at different steps. One study utilized the humanized anti-CD20 antibody obinutuzumab(single dose 1,000 mg 1.73m2) in combination with the anti-CD38 (plasmacells) monoclonal antibody daratumumab (1,000 mg 1.73m2)18 in patients who relapsed after conventional treatments with Prednisone, rituximab and CNI and developed dependence to the combination of more than 2 drugs (MDNS). A cohort of 14 patients treated with the above association were included in a retrospective analysis: all of them suspended oral drugs, 5 out of 14 presented recurrence of proteinuria after about 10 months, 9 out of 14 were in stable remission after 20 months. Therefore, the use of 2 monoclonal antibodies in low doses is potentially valuable considering the positive results and also taking in account the safety of the treatment. While it is not possible to discern the separate effects of obinutuzumab and daratumumab when given together, the preliminary positive results of their combination may open new ways in the treatment of nephrotic syndrome and supports the necessity of new studies in those patients who require more than one drug to maintain remission. The investigators hypothesize that rituximab in place of obinutuzumab (not available in Italy for the use in nephrotic syndrome) with daratumumab could produce the same positive effects in MDNS and MRNS.
The Dual 1 is a before-after clinical trial testing the superiority of rituximab plus daratumumab in maintaining drug free disease remission in patients with multi-drug dependent nephrotic syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase II Proof of concept, the Dual 1 is a before-after clinical trial testing the superiority of rituximab plus daratumumab in maintaining drug free disease remission in patients with multi-drug dependent nephrotic syndrome
| Arm | Type | Receives |
|---|---|---|
| single arm | Experimental | Drug: Rituximab Biosimilar ABP 798, Drug: Daratumumab |
Who may qualify
- Ages
- 3 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Age between 3 and 24 years
- Multidrug dependent or resistant nephrotic syndrome for at least six months before enrolment. The need of at least 2 of the oral drugs listed below defines multidrug-dependence: prednisone at any doses, MMF 1200 mg m2 and CNI 0.1 mg day given in two doses. Dependence is defined by two consecutive relapses during double therapies or within 14 days of ceasing one of the three components of the therapeutic approach. Resistance is defined as lack of antiproteinuric effect of a double therapy based on steroid plusCNI or mofetilmycophenolate (MMF).Steroid resistance is defined by failure to achieve complete remission after 6 weeks with prednisone60 mg/m2.
- Post transplant recurrence of FSGS.
- Ability to provide consent and assent: parents'/guardian's written informed consent, and child's assent given before any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject any time without prejudice to his or her future medical care.
Key exclusion criteria (8 listed)
- Positivity to autoimmunity tests (ANA, nDNA, ANCA)
- Reduction of C3 levels.
- eGFR<60/ml/min/1,73 m2 valuated according to revised Bedside Schwartz Formula for patients between 2 and 17 years and with CKD-EPI Creatinine 2009 Equation for 18 years old patients.
- Pregnancy
- Neoplasm
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 |
|---|---|---|
| Rituximab Biosimilar ABP 798Rituximab IV: the dose is standard for pediatric nephrotic syndrome; for dosage between 100 and 250 mg rituximab will be diluted in 100 ml of normal saline and administered at 2 ml/h for the first 30'; 3 ml/h for the second 30'; 6 ml/h for the third 30'; 15 ml/h until the end. For dosage between 260 and 500 mg rituximab will be diluted in 250 ml of normal saline and administered at 6 ml/h for the first 30'; 9 ml/h for the second 30'; 18 ml/h for the third 30'; 36 ml/h until the end. For dosage between 510 and 1000 mg rituximab will be diluted in 500 ml of normal saline and administered at 9 ml/h for the first 30'; thereafter, the infusion rate can be doubled every 30 minutes up to a maximum of 72 ml/h. | Drug | single arm |
| DaratumumabDaratumumab vials 20 mg 1 ml will be collected to reach the desired dose of 16 mg /Kg, the dose is standard recommend to treat myeloma; diluted in 1000 ml of normal saline and infused at the constant speed of 50 ml/h. This will be reduced in case of cutaneous allergic reactions | Drug | single arm |
Primary outcome
Safety- number of treatment-related adverse events
Time frame: 12 months
Primary: to test whether the combination of rituximab and daratumumab is safe and can achieve and maintain drug-free disease remission in patients with multi drug-dependent nephrotic syndrome within 12 months. The investigators will consider the number of participants with treatment-related adverse events as assessed by CTCAE v4.0 This outcome will not be compared but only studied following the intervention.
Efficacy- number of months in remission
Time frame: 12 months
To test whether the combination of rituximab and daratumumab can achieve and maintain drug-free disease remission in patients with multi drug-dependent nephrotic syndrome within 12 months The investigators will compare the outcome of log-albuminuria following the infusion of the two drugs to the log-albuminuria before the infusion, when patients were maintained by the association of MMF and CNI (i.e. the drug recommended by Clinical Practice Guidelines-KDIGO as benchmark of the treatment).
1 secondary outcome
Prediction
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2023.
- Derived from this study: PubMed 37705972Angeletti A, Bruschi M, Kajana X, La Porta E, Spinelli S, Caridi G, Lugani F, Verrina EE, Ghiggeri GM. Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment. Front Immunol. 2023 Aug 29;14:1213203. doi: 10.3389/fimmu.2023.1213203. eCollection 2023.
- Individual participant dataSharing planned: Yes. The completed study will be summarized in a final report that accurately and completely presents the study objectives, methods, results, limitations of the study, and interpretation of findings.
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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.
Gianmarco Ghiggeri, MD principal investigator
IRCCS G. Gaslini
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab Biosimilar ABP 798 and Daratumumab in people with Nephrotic Syndrome, run by Istituto Giannina Gaslini at 1 site in Italy.
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 4 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 31 Oct 2023. 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 Italy. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Gianmarco Ghiggeri, MD (+39010-56363523, gmarcoghiggeri@gaslini.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety- number of treatment-related adverse events (time frame: 12 months). The study lists 2 primary outcomes in all. 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 NCT05704400, 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 31 Oct 2023.