IgA NephropathyPhase 4NCT00498368
Rituximab in Progressive Immunoglobulin A (IgA) Nephropathy
A Phase 4 study testing Intravenous Rituximab, ACE/ARB and Omega-3 Fatty Acid Fish Oil Supplement in people with IgA Nephropathy, run by Mayo Clinic at 5 sites in United States.
Trial summary
This study was about IgA nephropathy, a form of kidney disease characterized by the presence of blood and protein in the urine. This study was done to determine if the medication rituximab could reduce protein in the patient's urine. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- IgA Nephropathy
- What is being tested?
- Intravenous Rituximab, ACE/ARB and Omega-3 Fatty Acid Fish Oil Supplement
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 5 sitesUnited States
- Study dates
- Feb 2009to Sep 2015
- Phase
- Phase 4
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any patient between the age of 18 and 70 years of age and able to give informed consent
- GFR by Cockcroft-Gault or MDRD equations <90 mls/min and >30 mls/min
- Greater than or equal to 1000 mg of proteinuria/24 hours while on stable ACEi, ARB or renin inhibitor therapy for 2 months. Patients receiving combination ACE or ARB or ACEi and a renin inhibitor for 2 months will only require 500mg/24 hours
- Blood pressure <130/80 mmHg. The presence of hypertension is not required for study entry, but any patient requiring long term hypertensive medications must have blood pressure controlled <130-80 mmHg, to be considered eligible for the study
- Female patients with IgA will be considered eligible for study entry if they have a negative urine or serum pregnancy test at the time of screening are agreeable to 2 years of contraception
- Biopsy proven IgA nephropathy and clinical features consistent with Henoch Schonlein Purpura will be considered eligible for the study
- Able to swallow the oral medications
Who cannot join
- Clinical and histologic evidence of IgA predominant Lupus nephritis
- Clinical and histologic evidence of idiopathic IgA forms of membranoproliferative glomerulonephritis
- Clinical evidence of cirrhosis, chronic active liver disease or known infection with hepatitis B, C or HIV
- Estimated GFR <30 ml/min/1.73m² at the time of screening
- Greater than 50% glomerular senescence or cortical scarring on renal biopsy
- Active systemic infection or history of serious infection within one month of entry
Show all 32Show fewer
- History of Crohn's disease or Celiac Sprue
- Positive pregnancy test or breast feeding at time of study entry or unwilling to comply with contraceptive measures
- Current or recent (within 30 days) exposure to any investigational drug
- Serum Cr >3.5 mg/dl or Modification of Diet in Renal Disease (MDRD) calculated GFR <30 mls/min
- Patients receiving >6 months therapy with oral prednisone or glucocorticoid equivalent
- Live vaccine within 28 days of study enrollment.
- General Safety \& Laboratory Exclusion Criteria
- Patients with anaphylaxis and/or known allergic reactions to Rituximab
- Hemoglobin: <8.5 gm/dL
- Platelets: <100,000/mm
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 x Upper Limit of Normal unless related to primary disease.
- Previous Treatment with Rituximab(MabThera®/Rituxan®)
- Previous treatment with Natalizumab(Tysabri®)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- History of recurrent significant infection or recurrent bacterial infections
- Known active bacterial, viral fungal mycobacterial or atypical mycobacterial infections, but excluding fungal infections of nail beds
- Any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- Ongoing use of high dose steroids(>10 mg/day)or unstable steroid dose in the past 4 weeks
- Lack of peripheral venous access
- History of drug, alcohol, or chemical abuse within 6 months prior to screening
- Pregnancy (a negative serum or urine pregnancy test will be performed for all women of childbearing potential no later than 7 days prior to treatment) or lactation
- Concomitant or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- History of psychiatric disorder that would interfere with normal participation in this protocol
- Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving 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 complication
- Inability to comply with study and follow-up procedures
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27599
The University of Ohio
Columbus, Ohio, 43210-1063
Columbia University Medical Center
New York, New York, 10032
Mayo Clinic
Rochester, Minnesota, 55905
Stanford University
San Francisco, California, 94304
About this study
Official title: A Multicenter, Randomized, Prospective, Open-Label Trial of Rituximab in the Treatment of Progressive IgA Nephropathy
This study was about IgA nephropathy, a form of kidney disease characterized by the presence of blood and protein in the urine. This study was done to determine if the medication rituximab could reduce protein in the patient's urine.
Hypothesis: In patients with progressive IgA nephropathy an intravenous infusion of 1000 mg of rituximab on Day 1 and Day 15 and Days 168 and 182 is superior to conventional therapy in reducing 24 hour proteinuria, and slowing progression of chronic kidney disease.
Read the detailed description
Recent clinical success in the use of Rituximab in the treatment of Lupus nephritis and other forms immune complex glomerulonephritis has led to its investigation in the treatment of IgA nephropathy. Because IgA class antibodies have comparatively short half-lives and that deposition of polymeric forms of IgA contributes to glomerular injury, the researchers speculated that the reduction of circulating IgA could reduce proteinuria and injury in patients with IgA nephropathy.
Treatment and Follow-up:
Subjects were randomly assigned to receive rituximab or to continue standard care. Both arms received a Omega-3 Fatty Acid Fish Oil Supplement and angiotensin converting enzyme (ACE) inhibitors and/or Angiotensin II receptor blockers (ARBs). ACE inhibitors and/or ARBs were used to achieve a blood pressure goal of <130/80 mmHg.
The study was an open-label trial; those assigned to rituximab received a 1 g infusion of rituximab followed by an identical dose 2 weeks later. Premedication with corticosteroids (10 mg dexamethasone intravenously) was also given 30 min prior to the first infusion of each series of rituximab. They received an identical 2 g course of rituximab 6 months later. Subjects were assessed at least every 3 months or as needed for clinical events. This assessment included physical examination, a questionnaire for adverse events, and measurement of routine hematology, serum chemistry, timed urine protein excretion, and for those assigned to rituximab, B-cell subsets. Follow-up was considered complete at 12 months.
- Conditions
- IgA Nephropathy
- Being tested
- Intravenous Rituximab, ACE/ARB, Omega-3 Fatty Acid Fish Oil Supplement
- Keywords
- Estimated glomerular filtration rate (GFR), Proteinuria, Renal Fibrosis
- Medical subject headings
- Glomerulonephritis, IGA, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous RituximabDrug
Also called Rituxan
Rituximab Therapy [27 Patients]
- Rituximab 1 gm IV on Treatment Day 1
- Rituximab 1 gm IV on Treatment Day 15
- Rituximab 1 gm IV on Treatment Day 168
- Rituximab 1 gm IV on Treatment Day 182
ACE/ARBDrug
Also called Angiotensin II blockade
ACE inhibitors and /or ARBs will be used to achieve a blood pressure goal of <130/80 millimeters of mercury (mmHg). Patients not attaining the target blood pressure with an ACE inhibitor or ARB alone should be treated with the combination of ACE inhibitor (ACEi) + ARB
Omega-3 Fatty Acid Fish Oil SupplementDietary supplement
Omega-3 Fatty Acid Fish Oil Supplement 3.6 gm eicosapentaenoic acid (EPA)/day
| Study group | Role | What they receive |
|---|---|---|
| Rituximab Plus ACE/ARB | Experimental | Intravenous Rituximab therapy, ACE/ARB combination therapy, and Omega-3 Fatty Acid Fish Oil Supplement Receives: Drug: Intravenous Rituximab; Drug: ACE/ARB; Dietary Supplement: Omega-3 Fatty Acid Fish Oil Supplement |
| ACE/ARB | Active comparator | ACE/ARB therapy and Omega-3 Fatty Acid Fish Oil Supplement Receives: Drug: ACE/ARB; Dietary Supplement: Omega-3 Fatty Acid Fish Oil Supplement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Proteinuria at 12 Months
Measured: 1 year
Secondary outcomes (3)
Biochemical Marker IgA at 12 Months
Measured: 12 months
Biochemical Marker Gd-Immunoglobulin A Subclass 1 (IgA1) at 12 Months
Measured: 12 months
Biochemical Marker Immunoglobulin G (IgG) AutoAb at 12 Months
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 posted10 Jul 2007 (estimated)
- Study startFeb 2009
- Primary completionSep 2015
- Study completionSep 2015
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for IgA NephropathyStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Ohio State University, Stanford University, University of North Carolina, Chapel Hill, Columbia University, Genentech, Inc., Biogen
- Responsible party
- Principal investigator, Fernando Fervenza, Mayo Clinic
- Investigators
- Fernando C. Fervenza, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00498368
- Sponsor's protocol ID
- 07-001944
- Status last verified
- Dec 2016
- First submitted
- 9 Jul 2007
- Last updated
- 1 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Lafayette RA, Canetta PA, Rovin BH, Appel GB, Novak J, Nath KA, Sethi S, Tumlin JA, Mehta K, Hogan M, Erickson S, Julian BA, Leung N, Enders FT, Brown R, Knoppova B, Hall S, Fervenza FC. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. J Am Soc Nephrol. 2017 Apr;28(4):1306-1313. doi: 10.1681/ASN.2016060640. Epub 2016 Nov 7.
PubMed 27821627Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.
PubMed 26032537
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Prospective, Open-Label Trial of Rituximab in the Treatment of Progressive IgA Nephropathy
- ClinicalTrials.gov ID
- NCT00498368
- Acronym / sponsor ID
- 07-001944
- Conditions
- IgA Nephropathy
- Keywords
- Estimated glomerular filtration rate (GFR), Proteinuria, Renal Fibrosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Ohio State University, Stanford University, University of North Carolina, Chapel Hill, Columbia University, Genentech, Inc., Biogen
- Study start
- Feb 2009
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 10 Jul 2007 (estimated)
- Results
- Posted 18 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study was about IgA nephropathy, a form of kidney disease characterized by the presence of blood and protein in the urine. This study was done to determine if the medication rituximab could reduce protein in the patient's urine.
Hypothesis: In patients with progressive IgA nephropathy an intravenous infusion of 1000 mg of rituximab on Day 1 and Day 15 and Days 168 and 182 is superior to conventional therapy in reducing 24 hour proteinuria, and slowing progression of chronic kidney disease.
Detailed description
Recent clinical success in the use of Rituximab in the treatment of Lupus nephritis and other forms immune complex glomerulonephritis has led to its investigation in the treatment of IgA nephropathy. Because IgA class antibodies have comparatively short half-lives and that deposition of polymeric forms of IgA contributes to glomerular injury, the researchers speculated that the reduction of circulating IgA could reduce proteinuria and injury in patients with IgA nephropathy.
Treatment and Follow-up:
Subjects were randomly assigned to receive rituximab or to continue standard care. Both arms received a Omega-3 Fatty Acid Fish Oil Supplement and angiotensin converting enzyme (ACE) inhibitors and/or Angiotensin II receptor blockers (ARBs). ACE inhibitors and/or ARBs were used to achieve a blood pressure goal of <130/80 mmHg.
The study was an open-label trial; those assigned to rituximab received a 1 g infusion of rituximab followed by an identical dose 2 weeks later. Premedication with corticosteroids (10 mg dexamethasone intravenously) was also given 30 min prior to the first infusion of each series of rituximab. They received an identical 2 g course of rituximab 6 months later. Subjects were assessed at least every 3 months or as needed for clinical events. This assessment included physical examination, a questionnaire for adverse events, and measurement of routine hematology, serum chemistry, timed urine protein excretion, and for those assigned to rituximab, B-cell subsets. Follow-up was considered complete at 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab Plus ACE/ARB | Experimental | Drug: Intravenous Rituximab, Drug: ACE/ARB, Dietary Supplement: Omega-3 Fatty Acid Fish Oil SupplementIntravenous Rituximab therapy, ACE/ARB combination therapy, and Omega-3 Fatty Acid Fish Oil Supplement |
| ACE/ARB | Active comparator | Drug: ACE/ARB, Dietary Supplement: Omega-3 Fatty Acid Fish Oil SupplementACE/ARB therapy and Omega-3 Fatty Acid Fish Oil Supplement |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Any patient between the age of 18 and 70 years of age and able to give informed consent
- GFR by Cockcroft-Gault or MDRD equations <90 mls/min and >30 mls/min
- Greater than or equal to 1000 mg of proteinuria/24 hours while on stable ACEi, ARB or renin inhibitor therapy for 2 months. Patients receiving combination ACE or ARB or ACEi and a renin inhibitor for 2 months will only require 500mg/24 hours
- Blood pressure <130/80 mmHg. The presence of hypertension is not required for study entry, but any patient requiring long term hypertensive medications must have blood pressure controlled <130-80 mmHg, to be considered eligible for the study
- Female patients with IgA will be considered eligible for study entry if they have a negative urine or serum pregnancy test at the time of screening are agreeable to 2 years of contraception
Key exclusion criteria (32 listed)
- Clinical and histologic evidence of IgA predominant Lupus nephritis
- Clinical and histologic evidence of idiopathic IgA forms of membranoproliferative glomerulonephritis
- Clinical evidence of cirrhosis, chronic active liver disease or known infection with hepatitis B, C or HIV
- Estimated GFR <30 ml/min/1.73m² at the time of screening
- Greater than 50% glomerular senescence or cortical scarring on renal biopsy
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 |
|---|---|---|
| Intravenous RituximabAlso: RituxanRituximab Therapy [27 Patients] * Rituximab 1 gm IV on Treatment Day 1 * Rituximab 1 gm IV on Treatment Day 15 * Rituximab 1 gm IV on Treatment Day 168 * Rituximab 1 gm IV on Treatment Day 182 | Drug | Rituximab Plus ACE/ARB |
| ACE/ARBAlso: Angiotensin II blockadeACE inhibitors and /or ARBs will be used to achieve a blood pressure goal of <130/80 millimeters of mercury (mmHg). Patients not attaining the target blood pressure with an ACE inhibitor or ARB alone should be treated with the combination of ACE inhibitor (ACEi) + ARB | Drug | ACE/ARB, Rituximab Plus ACE/ARB |
| Omega-3 Fatty Acid Fish Oil SupplementOmega-3 Fatty Acid Fish Oil Supplement 3.6 gm eicosapentaenoic acid (EPA)/day | Dietary supplement | ACE/ARB, Rituximab Plus ACE/ARB |
Primary outcome
Change in Proteinuria at 12 Months
Time frame: 1 year
3 secondary outcomes
Biochemical Marker IgA at 12 Months
Time frame: 12 months
Biochemical Marker Gd-Immunoglobulin A Subclass 1 (IgA1) at 12 Months
Time frame: 12 months
Biochemical Marker Immunoglobulin G (IgG) AutoAb at 12 Months
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 1 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27821627Lafayette RA, Canetta PA, Rovin BH, Appel GB, Novak J, Nath KA, Sethi S, Tumlin JA, Mehta K, Hogan M, Erickson S, Julian BA, Leung N, Enders FT, Brown R, Knoppova B, Hall S, Fervenza FC. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. J Am Soc Nephrol. 2017 Apr;28(4):1306-1313. doi: 10.1681/ASN.2016060640. Epub 2016 Nov 7.
- Derived from this study: PubMed 26032537Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.
- Individual participant dataSharing planned: Undecided
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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.
Fernando C. Fervenza, M.D. principal investigator
Mayo Clinic
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intravenous Rituximab, ACE/ARB and Omega-3 Fatty Acid Fish Oil Supplement in people with IgA Nephropathy, run by Mayo Clinic at 5 sites in United States.
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 7 inclusion and 32 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 1 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 18 Nov 2016). 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?
Change in Proteinuria at 12 Months (time frame: 1 year). 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 NCT00498368, which also lists 2 linked publications.
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 1 Feb 2017.