* To evaluate the efficacy of belimumab in combination with standard of care in adult subjects with lupus nephritis Class III, IV, or V using the 2003 ISN/RPS criteria. * To assess the safety and tolerability of belimumab plus standard of care…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Renal disorders (excl nephropathies)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Number of participants with Primary Efficacy Renal Response (PERR) at Week
104
Secondary outcome
- Complete Renal Response (CRR) at Week 104 (see definition under Ordinal Renal
Response).
- PERR at Week 52.
- Time to Death or Renal-related Event defined as any of the following: i) end
stage renal disease (ESRD), ii) doubling of serum creatinine, iii) renal
worsening as evidenced by increased proteinuria and/or impaired renal function,
or iv) renal disease-related treatment failure
- Ordinal Renal Response (ORR; complete, partial or no reponse) at Week 104
defined as follows:
- Complete Renal Response (CRR): Estimated glomerular filtration rate (GFR) is
no more than 10% below the pre-flare value or within normal range AND Urinary
protein:creatinine ratio <0.5 AND no receipt of prohibited (rescue) therapy
resulting in treatment failure (see Section 5.5 and Section 5.6)
- Partial Renal Response (PRR): Estimated GFR no more than 10% below the
baseline value or within normal range AND * 50% decrease in the urine protein:
creatinine ratio with one of the following: a urine protein:creatinine ratio of
< 1.0, if the baseline ratio was * 3.0 OR a urine protein:creatinine ratio of <
3.0, if the baseline ratio was > 3.0 AND No receipt of prohibited (rescue)
therapy resulting in treatment failure (see Section 5.5 and Section 5.6).
- No Renal Response (NRR): Not meeting criteria for either CRR or PRR.
Background summary
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder
characterized by autoantibody production and abnormal B lymphocyte function
(Pisetsky, 2001). The etiology of SLE is unknown, although genetics, sex
hormones, and environmental conditions are thought to play a role (Kotzin,
1996; Pisetsky, 1998; Sobel et al, 1999). This disease is more common in women
(~90% of patients) than men (NWHIC, 2003) and more prevalent in
African-Americans than Caucasians (OMHRC, 2001; NWHIC, 2003). In the United
States (US) the reported prevalence is 100,000 to 500,000 patients with some
estimates of 1 million as the incidence increased 2-3 fold between 1950 and
1979. In the European Union (EU), prevalence rates have been reported ranging
from 25 to 39 cases per 100,000 persons (Jimenez et al, 2003). In
community-based studies among Asians, the prevalence (per 100,000) of SLE
ranged from 3.2 to 70.4 (Thumboo and Wee, 2006). The disease onset is generally
between the ages of 20 and 40. Patients with SLE have about a 3-fold greater
risk of mortality than the general population. Approximately 70% of SLE
patients survive 20 years from time of diagnosis (Houssiau et al, 2004). SLE
can lead to arthritis, kidney failure, heart and lung inflammation, central
nervous system (CNS) changes, vasculitis, severe skin rash, and blood
dyscrasias such as anemia, leukopenia, and thrombocytopenia. The manifestations
of SLE vary from patient to patient and it may take many years to render the
proper diagnosis. The American College of Rheumatology (ACR) criteria that
define a diagnosis of this heterogeneous disease require 4 of 11 criteria that
include SLE-associated signs or symptoms, lab abnormalities, and the presence
of specific anti-nuclear autoantibodies (Tan et al, 1982). Approximately 35% of
all adult patients with SLE develop clinically significant lupus nephritis and
despite improvements in both diagnosis and treatment over the last few decades
it remains an indicator of poor prognosis (Gordon et al, 2009; Waldman and
Appel, 2006). Manifestations of lupus nephritis include proteinuria, elevations
in serum creatinine, and the presence of urinary sediment. Alongside these
clinical manifestations, morphological changes can be observed in renal biopsy
specimens. In 1975 the World Health Organization (WHO) proposed a
classification system for renal biopsies in SLE which was continually revised
by them up until 1995. In 2004 updated criteria jointly developed by the
International Society of Nephrology (ISN) and the Renal Pathology Society (RPS)
were published (Weening et al, 2004). Within the 5 overall classes, Classes I
and II reflect disease restricted to mesangial abnormalities. Classes III and
IV represent either focal (< 50% glomeruli involved - Class III) or diffuse
(\u2265 50% glomeruli involved - Class IV) segmental or global
glomerulonephritis. Class V represents membranous disease with Class VI
representing advanced sclerosis. Classes I and II are rarely accompanied by
clinical manifestations and there is no activity in Class VI only damage, so
therapy has traditionally focused on Classes III-V. Belimumab (BENLYSTA\u2122)
administered intravenously (IV) is approved in the US, Canada, and EU for the
treatment of adult patients with active autoantibody-positive SLE who are
receiving standard therapy; patients with severe active lupus nephritis and
severe active CNS lupus were excluded, as were patients receiving other
biologics and IV cyclophosphamide (refer to specific country labeling for
additional information regarding the approved indication). Approval of IV
belimumab for SLE is being sought in other regions of the world.
Study objective
* To evaluate the efficacy of belimumab in combination with standard of care in
adult subjects with lupus nephritis Class III, IV, or V using the 2003 ISN/RPS
criteria. * To assess the safety and tolerability of belimumab plus standard of
care versus placebo plus standard of care in adult subjects with lupus
nephritis Class III, IV, or V using the 2003 ISN/RPS criteria.
Study design
This is a Phase 3, multi-center, multi-national, randomized, double-blind,
placebo-controlled study to evaluate the efficacy and safety of IV belimumab 10
mg/kg plus standard of care compared to placebo plus standard of care in adult
subjects with active lupus nephritis. Subjects who meet the eligibility
criteria during screening will be randomized to 1 of 2 treatment groups in a
1:1 ratio: 10 mg/kg belimumab plus standard of care or placebo plus standard of
care. The randomization of all eligible subjects will be stratified by their
induction regimen (high dose cortiocsteroids [HDCS] plus CYC vs HDCS plus MMF)
and race (black race vs other). Subjects will be dosed with study agent on Days
0 (baseline), 14, 28, and then every 28 days thereafter through 100 weeks with
a final evaluation for the double-blind treatment period at 104 weeks. At least
400 and up to approximately 464 lupus nephritis subjects will be randomized
with a target of at least 200 and up to approximately 232 subjects in each
treatment group (belimumab or placebo). All subjects will receive background
therapy consisting of one of the following standard of care regimens: \u2022
High Dose Corticosteroids (HDCS) + Cyclophosphamide (CYC) for induction therapy
followed by Azathioprine (AZA) for maintenance therapy OR \u2022 HDCS +
Mycophenolate Mofetil (MMF) for induction followed by MMF for maintenance
therapy The standard of care medications are described in Section 5.5.1. Renal
response will be measured as complete, partial, or no response based on study
defined criteria (see Section 8.5). Week 104 renal response will be defined by
a response at Week 100 that is confirmed by a repeat measurement at Week 104.
Likewise, complete renal response at Week 104 will be defined by a complete
renal response at Week 100 that is confirmed by a repeat measurement at Week
104. All subjects who discontinue treatment with study agent during the
double-blind period (for reasons other than withdrawal of consent) should
return for all scheduled visits through Week 104. In the event that a subject
withdraws consent from the study, an attempt should be made to obtain consent
to collect follow-up safety data (at an exit visit approximately 4 weeks after
the last dose of study agent as well as a follow-up visit approximately 8 weeks
after the last dose of study agent) and to obtain survival status at Week 104.
Any subject that withdraws consent for use and disclosure of research-related
health information will be considered withdrawn from the study and will not be
followed for mortality. Subjects who receive treatment with study agent through
Week 100 and complete Week 104 assessments in the double-blind period may enter
into a 6-month open-label extension. The Week 104 visit of the double-blind
period will serve as the Day 0 visit for subjects entering the 6-month
open-label extension. In the open-label extension, all subjects will receive 10
mg/kg belimumab every 28 days until Week 24, with a final evaluation at Week 28
(4 weeks after the last dose). The first dose on the open-label extension will
be given at the Week 104 visit of the double-blind period following the
completion of all Week 104 assessments. Subjects participating in the
open-label extension will continue to be monitored for efficacy and safety as
per the study calendar (see Table 6-3). Subjects who complete the 104-week
double-blind period, but do not enter the open-label extension will be required
to return for an additional follow up visit 8 weeks after the last dose of
study agent. All subjects who enter the open-label extension period and
withdraw early will return for an Exit visit approximately 4 weeks after their
last dose of study agent as well as a follow-up visit approximately 8 weeks
after the last dose of study agent. At the end of the 6-month open-label
extension period, subjects who wish to continue treatment may do so by being
prescribed commercially available belimumab. If belimumab is not commercially
available in a subject\u2019s country of participation, the subject may
continue to receive belimumab under a separate continuation protocol if
permissible according to local regulations. A separate informed consent will
need to be provided for the continuation protocol. The 8 week follow-up visit
is not required for subjects entering the continuation protocol.
Intervention
In treatment phase the subjects will receive either belimumab or placebo
through IV at 28 of the 37 visits (inclusive 1 follow up visit). In the open
label phase all subjects will receive belimumab through IV at 6 of the 8 visits
(inclusive 1 follow up visit). More details can be found in Annex 3 of the
patient information sheet.
Study burden and risks
Belimumab administered by IV infusion is indicated for reducing disease
activity in adult patients with active autoantibody positive SLE who are
receiving standard therapy. The benefit/risk profile of belimumab for SLE
remains favorable. Identified risks include hypersensitivity/infusion reactions
and infections. Potential risks (i.e., based on pharmacology but no association
identified to date) include progressive multifocal leukoencephalopathy (PML),
malignancies, immunogenicity, effects on immunizations (including interactions
with live vaccine), and psychiatric events including depression and
suicidality. The most common AEs reported in the primary safety population of
adults with SLE were associated with hypersensitivity/infusion related
reactions, non opportunistic infections, and symptoms consistent with SLE. The
majority of reports of infusion-related and hypersensitivity reactions were
non-serious and include symptoms such as nausea, vomiting, diarrhea, chills,
fever, rash, urticaria, pruritus, headache, dizziness, and dyspnea. However,
infusion and hypersensitivity reactions can be severe and fatal. Infections
were commonly reported events with belimumab and are expected due to the
mechanism of action of belimumab and the SLE patient population. In the
post-marketing setting with IV belimumab, delayed onset of symptoms of acute
hypersensitivity reactions as well as recurrence of clinically significant
reactions after initial appropriate treatment has been observed. Subjects will
remain at the clinic for 3 hours following the first 2 infusions for
observation. Should symptoms of acute hypersensitivity occur, an extended
period of monitoring may be appropriate, based on clinical judgment. Subjects
should be made aware of the potential risk for severe or lifethreatening
hypersensitivity reactions, the signs and symptoms of such reactions, the
potential for delayed onset or recurrence of symptoms, and the importance of
immediately seeking medical attention should they occur. Belimumab should be
administered by a healthcare professional prepared to treat hypersensitivity
reactions including anaphylaxis. An Independent Data Monitoring Committee
(IDMC) reviews unblinded safety data for this Phase 3 study on an ongoing basis
until the data are locked and analyzed through Week 104. At all times the sites
and sponsor will remain blinded to treatment allocation. Events to be monitored
during the safety review include, at a minimum, all serious adverse events
(including deaths, serious psychiatric events, and serious infections), Grade 3
and Grade 4 laboratory abnormalities, opportunistic infections (serious and
nonserious), malignancies, and hypersensitivity/ anaphylactic reactions during
the double-blind and open-label extension portions of the study. Investigators
(and IRBs/IECs, as appropriate,) will be notified of the outcome of each IDMC
meeting. Benefit Assessment The primary data supporting efficacy of belimumab
were the Phase 3 trials (C1056 and C1057) in which 1,684 subjects including
those patients with renal manifestations were treated for up to 52 weeks
(C1057) or 76 weeks (C1056) (Belimumab IB, Section 5.3.1.2). Belimumab produced
significant improvements in the SLE Responder Index as well as in individual
component SELENA-SLEDAI score in both studies. Pooled analyses demonstrated
steroid sparing, delay in median time to first flare, and decreased risk of
severe flares over 52 weeks. In a post hoc analysis of the pooled data in
subjects with renal involvement at baseline, there were favorable trends of
greater reduction in proteinuria, hematuria, pyuria, and lower renal flare rate
with belimumab. These preliminary findings in patients with renal involvement
support that belimumab may provide potential benefit to these patients (Dooley
et al, 2013). Clinical trial data for belimumab since approval continue to show
efficacy in the treatment of SLE through decreased SLE flares and decreased
disease activity across multiple organ systems (Belimumab IB, Section 5.3.1.3;
Dooley et al, 2013). Overall Benefit:Risk Conclusion The safety profile of
belimumab remains consistent with that known at approval and is consistent with
expected events based on the mechanism of action and the disease under study.
Appropriate risk mitigation measures are in place; rare and long-term risks
will be further evaluated via the large safety study and registry, ongoing and
future studies, and routine pharmacovigilance. Review of safety data is
conducted on a continual basis in order to identify new safety signals which
may arise from clinical trial and/or post-marketing reports. The benefit: risk
profile of belimumab for SLE continues to be favorable. In addition, the
preliminary evidence suggests that patients with lupus nephritis may
potentially benefit from belimumab.
Belward Campus Drive 9910
Rockville, Maryland 20850
US
Belward Campus Drive 9910
Rockville, Maryland 20850
US
Listed location countries
Age
Inclusion criteria
1. Males or females at least 18 years of age.2. Have a clinical diagnosis
of systemic lupus erythematosus (SLE) according to the American College of
Rheumatology (ACR) criteria (Appendix 1).3. Have active, biopsy-proven
proliferative lupus nephritis Class III or IV [excluding Class III(C), IV-S(C),
and IV-G(C)] either with or without the presence of Class V, or pure Class V
membranous using the 2003 ISN/RPS criteria (Appendix 2); the biopsy must be
performed in the 6 months prior to the screening visit or during the screening
period. The local biopsy report will be used to confirm subject eligibility. A
tissue sample from the renal biopsy used to qualify the subject for
randomization needs to be sent to a central reading center after Day 0
(baseline).4. Have unequivocally positive anti-nuclear antibody (ANA) test
results defined as an ANA titer \u2265 1:80 (based on Hep-2 immunofluorescence
assay or equivalence by enzyme immunoassay assay), and/or a positive anti-dsDNA
(\u2265 30 IU/mL based on ELISA assay) serum antibody test at the screening
visit based on the study\u2019s central laboratory results.5. Have
documentation of active renal disease at screening requiring induction therapy
with high dose corticosteroids (HDCS) with either intravenous (IV)
cyclophosphamide (CYC) or mycophenolate mofetil (MMF) or other oral forms of
mycophenolate. The following factors will be used to define active renal
disease at screening: \u2022 Urinary protein:creatinine ratio of \u2265 1.0 AND
\uf02d Active urinary sediment as defined by at least 1 of the following (in
absence of menses and genitourinary tract infection). \uf02d - > 5 red blood
cell (RBC)/high power field (hpf) or above the laboratory reference range.
\uf02d - > 5 white blood cell (WBC)/hpf or above the laboratory reference
range. \uf02d - Presence of cellular casts (RBC or WBC). \uf02d - Subjects
without active urinary sediment are eligible if they meet at least 1 of the
following criteria:\uf02d *Have a confirmatory biopsy performed within 3 months
prior to the screening visit or during the screening period meeting the
criteria outlined in Inclusion Criterion 3. \uf02d *Have proteinuria \u2265 3.5
grams/day (or urinary protein:creatinine ratio\u2265 3.5).6. Have active
renal disease defined as above which requires induction therapy with high dose
corticosteroids (HDCS) with either intravenous (IV) cyclophosphamide (CYC) or
mycophenolate mofetil (MMF) or other oral forms of mycophenolate:Induction
therapy may begin before Screening but should be initiated within 60 days prior
to or on Day 0 (baseline). Initiation of induction is when both HDCS and either
MMF or CYC have been started.The study recommended doses for induction therapy
are as follows, adjustments may be made for tolerability issues (refer to
Section 5.5.1 Standard of Care Medication for details):- MMF 1-3g/day orally or
Mycophenolate sodium 720 - 2160 mg/day orally - corticosteroids: 0-3 IV pulses
of methylprednisolone 500 -1000 mg/pulse followed by oral prednisone 0.5-1.0
mg/kg/day with total daily dose up to 60 mg/day (or equivalence)- CYC 500 mg by
IV infusion every 2 weeks (\uf0b1 3 days) for 6 infusionsSubjects who have been
on MMF for SLE including lupus renal disease may be eligible if they have
received, or will receive, the following induction therapy within 60 days prior
to or on Day 0:- initiation of HDCS with MMF dose increase to reach the target
dose for induction in the subject (if the subject did not previously fail MMF
induction based on the investigator\u2019s opinion), OR- initiation of HDCS
with discontinuation of MMF and initiation of CYC.Note: It is recommended that
subject eligibility should be discussed with the Medical Monitor if a subject
initiated but did not complete an induction therapy within 6 months prior to
the initiation of current induction therapy for the study.7. A female subject
is eligible to enter the study if she is: \u2022 Not pregnant or nursing;
\u2022 Of non-childbearing potential (ie, women who had a hysterectomy, are
postmenopausal which is defined as 1 year without menses, have both ovaries
surgically removed, or have current documented tubal ligation or any other
permanent female sterilization procedure); or \u2022 Of childbearing potential
(ie, women with functional ovaries and no documented impairment of oviductal or
uterine function that would cause sterility). This category includes women with
oligomenorrhoea [even severe], women who are perimenopausal, or have just begun
to menstruate. These women must have a negative serum pregnancy test at
screening, and agree to 1 of the following:\uf02d *Complete abstinence from
intercourse from 2 weeks prior to administration of the 1st dose of study agent
until 16 weeks after the last dose of study agent; or \uf02d *Consistent and
correct use of 1 of the following acceptable methods of birth control for 1
month prior to the start of the study agent, during study, and for 16 weeks
after the last dose of study agent:\u25e6 Implants of levonorgestrel or
etonogestrel; \u25e6 Ethinyl estradiol/Etonogestrel vaginal ring; \u25e6
Injectable progesterone; \u25e6 Any intrauterine device (IUD) with a documented
failure rate of less than 1% per year; \u25e6 Oral contraceptives (either
combined or progesterone only); \u25e6 Double barrier method: condom and
occlusive cap (diaphragm or cervical/vault caps) with spermidical
foam/gel/film/cream/suppository; \u25e6 Transdermal contraceptive patch; \u25e6
Male partner sterilisation with documentation of azoospermia prior to the
female subject\u2019s entry into the study, and this male is the sole partner
for that subject. The documentation on male sterility can come from the site
personnel\u2019s review of subject\u2019s medical records, medical examination
and/or semen analysis, or medical history interview provided by her or her
partner.Note: If stricter female or male contraception requirements are
specified in the country-specific label for induction and/or maintenance
standard of care medications, they must be followed.8. Have the ability to
understand the requirements of the study, provide written informed consent
(including consent for the use and disclosure of research-related health
information), and comply with the study protocol procedures (including required
study visits).
diaboxwideÌ
Exclusion criteria
1. Subjects who have previously failed both CYC and MMF (or other forms of
mycophenolate) induction therapies based on the investigator\u2019s opinion. If
a subject has failed only 1 of the 2 therapies for induction, they may be
eligible for study inclusion if the other induction therapy is initiated within
60 days prior to or on Day 0 (ie, a subject who failed MMF is eligible if newly
initiating induction therapy with CYC or a subject who failed CYC is eligible
if newly initiating induction therapy with MMF).2. Subjects who received an
induction therapy with CYC within 3 months prior to the planned initiation of
the current induction for the study.3. Subjects who receive CYC whose
pre-induction leukocyte count is Grade 3 or 4 based on the Adverse Event
Severity Grading Tables (Appendix 7).4. Known hypersensitivity or
contraindication to any drug products or any component of these drug products
they plan to receive (eg, CYC, MMF, azathioprine (AZA), corticosteroids).5.
Have a history of an anaphylactic reaction to parenteral administration of
contrast agents, human or murine proteins or monoclonal antibodies.6. Have
received treatment with belimumab within 364 days of baseline (Day 0).7.
Received any of the following within 364 days of baseline (Day 0): Nitrogen
mustard Chlorambucil Vincristine Procarbazine Etoposide Abatacept Treatment
with any B cell targeted therapy (eg, rituximab, other anti-CD20 agents,
anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein
[BR3], TACI-Fc, or LY2127399 [anti-BAFF]) A biologic investigational agent (eg,
abetimus sodium, anti-CD40L antibody [BG9588/ IDEC-131]). Investigational agent
applies to any drug not approved for sale in the country in which it is being
used. Treatment with interleukin-6 targeted therapy (e.g., tocilizumab,
sirukumab).8. Received any of the following within 90 days of baseline (Day 0):
Anti-TNF therapy (eg, adalimumab, etanercept, infliximab, certolizumab,
golimumab pegol) Interleukin-1 receptor antagonist (anakinra). Intravenous
immunoglobulin (IVIG). Plasmapheresis.9. Received a non-biological
investigational agent within 60 days of baseline (Day 0).10. Received a live
vaccine within 30 days of baseline (Day 0).11. Have severe active central
nervous system (CNS) lupus (including seizures, psychosis, organic brain
syndrome, cerebrovascular accident [CVA], cerebritis, or CNS vasculitis)
requiring therapeutic intervention within 60 days of baseline (Day 0). 12. Have
a history of a major organ transplant (eg, heart, lung, kidney, liver) or
hematopoietic stem cell/marrow transplant or are due to receive
transplantation.13. Subjects who have been on dialysis within 364 days of
baseline (Day 0).14. An estimated glomerular filtration rate < 30
mL/min/1.73m\262 at the screening visit (using the simplified Modification of
Diet in Renal Disease [MDRD] equation).15. Have clinical evidence of
significant unstable or uncontrolled acute or chronic diseases not due to SLE
(ie, cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal,
neurological, malignancy, or infectious diseases) which, in the opinion of the
principal investigator, could confound the results of the study or put the
subject at undue risk.16. Have a planned surgical procedure or a history of any
other medical disease (eg, cardiopulmonary), laboratory abnormality, or
condition (eg, poor venous access) that, in the opinion of the principal
investigator, makes the subject unsuitable for the study.17. Have a history of
malignant neoplasm within the last 5 years, except for adequately treated
cancers of the skin (basal or squamous cell) or carcinoma in situ of the
uterine cervix.18. Have acute or chronic infection requiring management, as
follows: \uf02d Currently on any suppressive therapy for a chronic infection
(such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus,
herpes zoster, or atypical mycobacteria). \uf02d Hospitalization for treatment
of infection within 60 days of baseline (Day 0). \uf02d Have had infection
requiring treatment with parenteral (IV or IM) antibiotics (antibacterials,
antivirals, anti-fungals, or anti-parasitic agents) within 60 days of baseline
(Day 0).19. Have current drug or alcohol abuse or dependence, or a history of
drug or alcohol abuse or dependence within 364 days prior to baseline (Day
0).20. Have a historically positive test or test positive at screening for HIV
antibody.21. Hepatitis B: Serologic evidence of Hepatitis B (HB) infection
based on the results of testing for HBsAg, anti-HBc and anti-HBs as follows:
\uf02d Patients positive for HBsAg are excluded. \uf02d Patients negative for
HBsAg but positive for Anti-HBc, regardless of Anti-HBs antibody status, will
require clarification of their status by testing for HBV DNAo if HBV DNA
positive, patients will be excluded from participation o if HBV DNA negative,
patients will be eligible to enrol. NOTE: For those subjects randomised,
additional ongoing assessment during the study is required (see Section
6.7.5).22. Hepatitis C: Positive test for Hepatitis C antibody confirmed on a
subsequent blood sample by RNA-PCR assay. Subjects who are positive for
Hepatitis C antibody and negative when the Hepatitis C RNA-PCR assay is
performed on a subsequent sample will be eligible to participate. Subjects who
are positive for Hepatitis C antibody and have a positive result for the HCV
when the Hepatitis C RNA-PCR assay is performed on the subsequent sample will
not be eligible to participate. Subjects in China with positive test for
Hepatitis C antibody will be excluded without confirmatory Hepatitis C RNA-PCR
testing.23. Have an IgA deficiency (IgA level < 10 mg/dL).24. Have a Grade 3 or
greater laboratory abnormality (including serum IgG level) based on the Adverse
Event Severity Grading Tables (Appendix 7) except for the following that are
allowed: \uf02d Urinalysis (eg, proteinuria) \uf02d Hematuria \uf02d Pyuria
\uf02d Casts \uf02d Hypoalbuminemia due to lupus nephritis \uf02d Stable Grade
3 prothrombin time (PT) secondary to warfarin treatment. \uf02d Stable Grade 3
partial thromboplastin time (PTT) due to lupus anticoagulant and not related to
liver disease or anti-coagulant therapy. \uf02d Stable Grade 3 gamma glutamyl
transferase (GGT) elevation due to lupus hepatitis, and not related to
alcoholic liver disease, uncontrolled diabetes or viral hepatitis. If present,
any abnormalities in the ALT and/or AST must be \u2264 Grade 2. \uf02d Stable
Grade 3 reduction in hemoglobin levels due to SLE \uf02d Stable Grade 3
neutropenia or stable Grade 3 white blood cell count [with the exception of
subjects receiving CYC who will be excluded if WBC is Grade 3 or 4 per
Exclusion Criterion 3]. Note that WBC count should be obtained immediately
prior to starting induction therapy. If immediate pre-induction WBC is not
available, a WBC count obtained within 28 days prior to induction may be used.
\uf02d Hyperuricemia or blood urea nitrogen (BUN) elevation due to lupus
nephritis or SLE.25. Subjects who have evidence of serious suicide risk
including any history of suicidal behavior in the last 6 months and/or any
suicidal ideation of type 4 or 5 on the Columbia- Suicide Severity Rating Scale
(C-SSRS) (Appendix 8) in the last 2 months or who, in the investigator\'s
opinion, pose a significant suicide risk.].Klasse_10;
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Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011\u20100045-NL |
| ClinicalTrials.gov | NCT01639339 |
| CCMO | NL53821.056.15 |