Primary Focal Segmental GlomerulosclerosisPhase 2NCT01573533
A Pilot Study to Assess the Efficacy of Rituximab Therapy in Treatment Resistant FSGS
A Phase 2 study testing Rituximab in people with Primary Focal Segmental Glomerulosclerosis, run by Mayo Clinic at 4 sites in 2 countries.
Trial summary
The purpose of this study is to determine whether Rituximab therapy is safe and effective in treating patients with the kidney condition, focal segmental glomerulosclerosis (FSGS), that is no longer responsive to traditional therapies. Read more about this study
- Who is it for?
- Ages 6 to 80 years
- Conditions the study is for
- Primary Focal Segmental Glomerulosclerosis
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Oct 2013to 15 Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 6 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- FSGS involving native kidneys with a diagnostic biopsy performed within the last 3 years
- Patients >6 years of age and < 80 years of age
- suPAR > 3500 pg ml-1
- Treatment with an ACEI and/or ARB as tolerated for at least 3 months prior to enrollment to with a target a systolic blood pressure ≤ 140 mmHg and a diastolic pressure ≤ 90 mmHg in adults and blood pressure readings less than the 95th percentile for age, gender and height in children in at least 75% of readings
- Proteinuria ≥ 3.0 grams as measured by 24-hour urine collection in adults and urine protein:creatinine ratio ≥ 1.0 in the first morning urine in children, despite ACE inhibitor / ARB treatment as tolerated and a minimum of 8 weeks of prednisone therapy at ≥ 1 mg/kg/day, a trial of calcineurin inhibitor for=> 3 months or a contraindication/intolerance to such therapy (diabetes, osteoporosis/osteonecrosis, age >60, BMI ≥35)
- Negative serum pregnancy test (for women of child bearing age)
- Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of the trial
- Able and willing to give written informed consent and comply with study requirements
Who cannot join
- Estimated GFR < 40 ml/min per1.73m2. The rationale is that patients with advanced renal failure may progress rapidly towards ESRD.
- Collapsing variant of FSGS, as it is rare and has been associated with an aggressive course
- Concurrent use of immunosuppressive therapy with the exceptions of prednisone 10 mg/day. Patients who are taking other immunosuppressive therapy, must be off immunosuppressive medications for equal to or > 3 months prior to enrollment into the study with the exception of patients demonstrating significant worsening of proteinuria (of >30% above baseline) during the washout period. These resistant patients can be treated after 1 month of washout due to the high likelihood of progression and/or lack of delayed (previous) immunosuppression effect.
- Patients with medical conditions that may cause FSGS (e.g. HIV, lymphoma, heroin use) or have a secondary form of FSGS due to hyperfiltration injury (massive obesity, vesicoureteral reflux, or renal mass reduction)
- Type 1 or type 2 diabetes mellitus as diabetic glomerulosclerosis may be contributing to proteinuria in these patients
- History of serious recurrent or chronic infection
Show all 17Show fewer
- Presence or suspicion of active infection including TB, HIV, Hepatitis B and HCV with positive tests for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B virus (HBV), Hepatitis C serology, HIV serology or a positive TB skin test, which require further investigation to rule out active disease (ie. chest x-ray)
- Known active infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks or oral antibiotics within 2 weeks of the study initiation
- Low immunoglobulins (level to be based on age)
- Absolute neutrophil count < 1.5 x103/mL
- Patients in receipt of a live vaccine within 4 weeks of the study initiation
- Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- Previous Treatment with a B-cell depleting antibody
- History of severe allergic reactions to humanized or murine monoclonal antibodies
- Treatment with any investigational agent within 4 weeks of the study initiation
- History of major psychiatric disorder, drug or alcohol abuse within the previous 6 months
- Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory that provides a reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States2 sites
Rush University Medical Center
Chicago, Illinois, 60612
Mayo Clinic College of Medicine
Rochester, Minnesota, 55905
Canada2 sites
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
University Health Network
Toronto, Ontario, M5G 2N2
About this study
Official title: A Pilot Study to Assess the Efficacy of Rituximab Therapy in Patients With Treatment Resistant Idiopathic Focal Segmental Glomerulosclerosis (FSGS): Integrating an Assessment of the Relevance of suPAR and Activation of Podocyte β3 Integrin
The purpose of this study is to determine whether Rituximab therapy is safe and effective in treating patients with the kidney condition, focal segmental glomerulosclerosis (FSGS), that is no longer responsive to traditional therapies.
Read the detailed description
This is a pilot trial to assess the safety, feasibility and efficacy of Rituximab therapy in 20 adult and pediatric patients with either steroid and/or calcineurin inhibitor resistant FSGS or with a significant intolerance or contraindication to the use of these agents. In addition to clinical criteria, elevated levels of suPAR will define inclusion. Changes in the baseline levels of the potential biomarkers (suPAR, as well as activation of beta-3 integrin) in response to treatment will be compared to clinical measures of efficacy.
Participants will have a screening/baseline visit to confirm eligibility within 6 weeks prior to the first of two Rituximab infusions (at Day 1 and Day 15). Participants will then attend follow up visits at 1, 3, 6 and 12 months after Rituximab treatment to assess adverse events and collect safety blood and urine samples.
- Being tested
- Rituximab
- Keywords
- Treatment Resistant Idiopathic FSGS, Glomerulosclerosis, Proteinuria, Rituximab
- Medical subject headings
- Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabBiological
Also called Rituxan®
Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Not described Receives: Biological: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Proteinuria (With Stable Renal Function)
The amount of protein in excreted urine measured by grams per day (g/day). Remission status defined by the following criteria at 12 months:
- Complete Remission - Proteinuria < 0.5 g/day
- Partial Remission - Improvement in proteinuria by > 50% and to a level between 0.5-3.5g/day
- Incomplete Remission - Improvement in proteinuria equal to or >50%, but residual proteinuria still >3.5g/day
Measured: Baseline, 12 months
Secondary outcomes (3)
Change in suPAR Levels
SuPAR concentrations will be determined by quantitative ELISA immunoassay reported in picograms per milliliters (pg/ml)
Measured: Baseline, 1, 3, 6 and 12 months
Change in Activation of Podocyte β3 Integrin
To quantitatively examine the effect of FSGS patient sera on podocyte β3 integrin activity, a human podocyte cell line is cultured at 37 degrees Celsius for 14 days for complete differentiation. The cells are then incubated in 5-10% of FSGS patient serum for 24 hours with recombinant suPAR protein as a positive control. Cells are fixed with 4% paraformaldehyde (PFA) and proceeded for immunofluorescence staining for AP5 and paxillin. After immunostaining, confocal images are taken to quantify the AP5 and paxillin intensity for each sample treatment. Paxillin signal is used to correct AP5 signal. The relative AP5 signal (AP5/paxillin ratio) from each patient serum is then normalized against that of normal blood donor included in each assay for final report.
Measured: Baseline, 1, 3, 6, 12 months
Number of Subjects With Complete or Partial Remission Following Treatment
Total number of subjects with complete or partial remission following treatment using the following criteria:
- Complete Remission - Proteinuria < 0.5 g/day
- Partial Remission - Improvement in proteinuria by > 50% and to a level between 0.5-3.5g/day
- Incomplete Remission - Improvement in proteinuria equal to or >50%, but residual proteinuria still >3.5g/day
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 posted9 Apr 2012 (estimated)
- Study startOct 2013
- Primary completion15 Nov 2018
- Study completion15 Nov 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Focal Segmental GlomerulosclerosisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto, National Institutes of Health (NIH), Genentech, Inc., Rush University Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Principal investigator, Fernando Fervenza, Mayo Clinic
- Investigators
- Michelle Hladunewich, MD, MSc, BSc, Principal investigator, University Health Network, Sunnybrook Health Sciences CentreFernando C Fervenza, MD, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01573533
- Sponsor's protocol ID
- 12-005640
- Other IDs
- U54DK083912
- Status last verified
- Jan 2020
- First submitted
- 5 Apr 2012
- Last updated
- 10 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess the Efficacy of Rituximab Therapy in Patients With Treatment Resistant Idiopathic Focal Segmental Glomerulosclerosis (FSGS): Integrating an Assessment of the Relevance of suPAR and Activation of Podocyte β3 Integrin
- ClinicalTrials.gov ID
- NCT01573533
- Acronym / sponsor ID
- 12-005640
- Keywords
- Treatment Resistant Idiopathic FSGS, Glomerulosclerosis, Proteinuria, Rituximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- University Health Network, Toronto, National Institutes of Health (NIH), Genentech, Inc., Rush University Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Oct 2013 (actual)
- Primary completion
- 15 Nov 2018 (actual)
- Study completion
- 15 Nov 2018 (actual)
- First posted
- 9 Apr 2012 (estimated)
- Results
- Posted 10 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether Rituximab therapy is safe and effective in treating patients with the kidney condition, focal segmental glomerulosclerosis (FSGS), that is no longer responsive to traditional therapies.
Detailed description
This is a pilot trial to assess the safety, feasibility and efficacy of Rituximab therapy in 20 adult and pediatric patients with either steroid and/or calcineurin inhibitor resistant FSGS or with a significant intolerance or contraindication to the use of these agents. In addition to clinical criteria, elevated levels of suPAR will define inclusion. Changes in the baseline levels of the potential biomarkers (suPAR, as well as activation of beta-3 integrin) in response to treatment will be compared to clinical measures of efficacy.
Participants will have a screening/baseline visit to confirm eligibility within 6 weeks prior to the first of two Rituximab infusions (at Day 1 and Day 15). Participants will then attend follow up visits at 1, 3, 6 and 12 months after Rituximab treatment to assess adverse events and collect safety blood and urine samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Biological: Rituximab |
Who may qualify
- Ages
- 6 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- FSGS involving native kidneys with a diagnostic biopsy performed within the last 3 years
- Patients >6 years of age and < 80 years of age
- suPAR > 3500 pg ml-1
- Treatment with an ACEI and/or ARB as tolerated for at least 3 months prior to enrollment to with a target a systolic blood pressure ≤ 140 mmHg and a diastolic pressure ≤ 90 mmHg in adults and blood pressure readings less than the 95th percentile for age, gender and height in children in at least 75% of readings
- Proteinuria ≥ 3.0 grams as measured by 24-hour urine collection in adults and urine protein:creatinine ratio ≥ 1.0 in the first morning urine in children, despite ACE inhibitor / ARB treatment as tolerated and a minimum of 8 weeks of prednisone therapy at ≥ 1 mg/kg/day, a trial of calcineurin inhibitor for=> 3 months or a contraindication/intolerance to such therapy (diabetes, osteoporosis/osteonecrosis, age >60, BMI ≥35)
Key exclusion criteria (17 listed)
- Estimated GFR < 40 ml/min per1.73m2. The rationale is that patients with advanced renal failure may progress rapidly towards ESRD.
- Collapsing variant of FSGS, as it is rare and has been associated with an aggressive course
- Concurrent use of immunosuppressive therapy with the exceptions of prednisone 10 mg/day. Patients who are taking other immunosuppressive therapy, must be off immunosuppressive medications for equal to or > 3 months prior to enrollment into the study with the exception of patients demonstrating significant worsening of proteinuria (of >30% above baseline) during the washout period. These resistant patients can be treated after 1 month of washout due to the high likelihood of progression and/or lack of delayed (previous) immunosuppression effect.
- Patients with medical conditions that may cause FSGS (e.g. HIV, lymphoma, heroin use) or have a secondary form of FSGS due to hyperfiltration injury (massive obesity, vesicoureteral reflux, or renal mass reduction)
- Type 1 or type 2 diabetes mellitus as diabetic glomerulosclerosis may be contributing to proteinuria in these patients
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 |
|---|---|---|
| RituximabAlso: Rituxan®Rituximab will be infused intravenously on Day 1 and Day 15 at a dose of 375 mg/m2 up to a maximum of 1000mg per dose in children and at a dose of 1000 mg on Day 1 and Day 15 in adults. | Biological | Rituximab |
Primary outcome
Changes in Proteinuria (With Stable Renal Function)
Time frame: Baseline, 12 months
The amount of protein in excreted urine measured by grams per day (g/day). Remission status defined by the following criteria at 12 months: * Complete Remission - Proteinuria < 0.5 g/day * Partial Remission - Improvement in proteinuria by > 50% and to a level between 0.5-3.5g/day * Incomplete Remission - Improvement in proteinuria equal to or >50%, but residual proteinuria still >3.5g/day
3 secondary outcomes
Change in suPAR Levels
Time frame: Baseline, 1, 3, 6 and 12 months
Change in Activation of Podocyte β3 Integrin
Time frame: Baseline, 1, 3, 6, 12 months
Number of Subjects With Complete or Partial Remission Following Treatment
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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.
Michelle Hladunewich, MD, MSc, BSc principal investigator
University Health Network, Sunnybrook Health Sciences Centre
Fernando C Fervenza, MD, PhD principal investigator
Mayo Clinic
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab in people with Primary Focal Segmental Glomerulosclerosis, run by Mayo Clinic at 4 sites in 2 countries.
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 17 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 10 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Canada. 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?
Yes. Results are posted in the registry (first posted 10 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in Proteinuria (With Stable Renal Function) (time frame: Baseline, 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Feb 2020.