Phase 2
N=43
Rituximab and Belimumab for Lupus Nephritis
Lupus Nephritis
Bottom Line
View on ClinicalTrials.gov: NCT02260934 ↗Enrolled (actual)
43
Serious AEs
22.1%
Results posted
Apr 2019
Primary outcome: Primary: Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 — 9.1; 4.8; 22.7; 9.5 percentage of participants — p=0.58
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Rituximab (Biological); Cyclophosphamide (Drug); Prednisone (Drug); Methylprednisolone (Drug); Diphenhydramine (Drug); Acetaminophen (Drug); Belimumab (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Mar 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With At Least One Grade 3 or Higher Infectious Adverse Event By Week 24, Week 48 and Week 96 |
9.1; 4.8; 22.7; 9.5; 27.3; 9.5 | 0.58 |
| SECONDARY Percentage of Participants With B Cell Reconstitution at Week 24, Week 48 and Week 96 |
31.3; 6.3; 35.7; 11.8; 40.0; 30.8 | — |
| SECONDARY Percentage of Participants With Grade 4 Hypogammaglobulinemia by Week 24, Week 48, and Week 96 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With a Complete Response at Week 24, Week 48, and Week 96 |
23.8; 30.0; 35.0; 42.1; 33.3; 42.9 | 0.66 |
| SECONDARY Percentage of Participants With an Overall Response at Week 24, Week 48, and Week 96 |
46.7; 55.0; 60.0; 73.7; 53.3; 71.4 | 0.64 |
| SECONDARY Percentage of Participants With a Sustained Complete Response |
26.7; 28.6 | 0.91 |
| SECONDARY Percentage of Participants With Treatment Failure by Week 24, Week 48, and Week 96 |
18.2; 14.3; 45.5; 28.6; 63.6; 47.6 | .73 |
| SECONDARY Count of Participants: Frequency of Non-renal Flares by Week 24 |
21; 20; 1; 0; 0; 1 | >0.99 |
| SECONDARY Count of Participants: Frequency of Non-renal Flares by Week 48 |
20; 20; 2; 0; 0; 1 | 0.49 |
| SECONDARY Count of Participants: Frequency of Non-renal Flares by Week 96 |
18; 19; 4; 1; 0; 1 | — |
| SECONDARY Percentage of Participants With an Negative Anti-dsDNA Result at Week 24, Week 48, and Week 96 |
14.3; 15.8; 20.0; 30.0; 0.0; 27.8 | 0.89 |
| SECONDARY Percentage of Participants Hypocomplementemic for Complement Component C3 at Week 24, Week 48, and Week 96 |
57.1; 30.0; 55.0; 30.0; 61.1; 27.8 | 0.08 |
| SECONDARY Percentage of Participants Hypocomplementemic for Complement Component C4 at Week 24, Week 48, and Week 96 |
19.0; 5.0; 15.0; 15.0; 16.7; 11.1 | .20 |
| SECONDARY Frequency of Specific Adverse Events of Interest By Event by Week 96 |
0; 0; 13; 16; 0; 0 | — |
| SECONDARY Frequency of Specific Adverse Events of Interest By Participant, By Week 96 |
0; 0; 6; 6; 0; 0 | — |
Summary
In this experimental study, researchers will try to find out if treatment of lupus nephritis with a combination of rituximab and cyclophosphamide (CTX), or a combination of rituximab and CTX followed by treatment with belimumab is safe and if this drug combination can block the immune system attacks.
Eligibility Criteria
Inclusion Criteria
- Diagnosis of Systemic Lupus Erythematosus (SLE) by American College of Rheumatology (ACR) criteria.
- Positive antinuclear antibody (ANA) or positive anti-ds DNA test results at visit -1 or any time within 14 days before visit -1.
- Active proliferative lupus nephritis, as defined by either of the following:
- Kidney biopsy documentation within the last 3 months of International Society of Nephrology/Renal Pathology Society (ISN/RPS) proliferative nephritis: Class III, Class IV, or Class V in combination with Class III or IV.
- Active urinary sediment and kidney biopsy documentation within the last 12 months of ISN/RPS proliferative nephritis: Class III, Class IV, or Class V in combination with Class III or IV. Active urinary sediment is defined as any one of the following:
- >5 RBC/hpf in the absence of menses and infection;
- >5 White blood cell per high powered field (WBC/hpf) in the absence of infection; or
- Cellular casts limited to RBC or WBC casts.
- Urine protein-to-creatinine ratio (UPCR) >1 at study entry based on a 24-hour collection.
- Ability to provide informed consent.
Exclusion Criteria
- New onset lupus nephritis, defined as lupus nephritis for which the participant has not yet been treated with either mycophenolate mofetil or cyclophosphamide.
- Neutropenia (absolute neutrophil count =2 times the upper limit of normal.
- Severe, progressive, or uncontrolled renal, hepatic, hematological,gastrointestinal, pulmonary, cardiac, or neurological disease, either related or unrelated to SLE, with the exception of active lupus nephritis (or, in the investigator's opinion, any other concomitant medical condition that places the participant at risk by participating in this study).
- Comorbidities requiring corticosteroid therapy, including those which have required three or more courses of systemic corticosteroids within the previous 12 months.
- Current substance abuse or history of substance abuse within the past year.
- History of severe allergic or anaphylactic reactions to chimeric or fully human monoclonal antibodies.
- History of anaphylactic reaction to parenteral administration of contrast agents.
- Lack of peripheral venous access.
- History of severe depression or severe psychiatric condition.
- History of suicidal thoughts within the past 2 months or suicidal behavior within the past 6 months, or a significant suicide risk in the investigator's opinion.
- Inability to comply with study and follow-up procedures.
Data sourced from ClinicalTrials.gov (NCT02260934). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.