Available via license: CC BY-NC 4.0
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Methods The IMPACT Study (IMProve Pregnancy in APS
with Certolizumab Therapy) is an open label single-stage
Phase II trial to evaluate the effect of certolizumab, a TNF-a
inhibitor that does not cross the placenta and has been shown
to be well tolerated in pregnancy, to reduce the risk of
adverse outcomes in this population. Patients with APS and
LAC are referred to IMPACT by their physicians, consented
and screened remotely by a study investigator, and medication
is sent to the patient. They are treated with certolizumab
from gestational week 8 through 28. Investigators contact
patients every 2 weeks and receive medical reports and
research blood samples monthly. The primary outcome is a
composite of two APOs associated with poor placentation:
fetal death >10 WG or severe preeclampsia/placental insuffi-
ciency requiring delivery prior to 34 weeks gestation. The tar-
get sample size is 45 evaluable subjects. We hypothesize that
the rate of the primary outcome in these pregnancies will be
reduced from ~40% based on historical data to 20% with
certolizumab.
Results Since May 2017 and despite the COVID-19 pandemic,
we have enrolled 41 patients from ten states and 1 Canadian
province. Characteristics: 56% previous PE or PI <34 weeks
requiring delivery, 83% previous fetal death >10 weeks; 61%
thrombosis and/or stroke and 24% SLE in addition to APS.
During the trial, no new clinical manifestations of SLE have
been observed in participants who did not carry the SLE diag-
nosis. There were no instances of new anti-DNA antibodies or
increases in autoantibody titres in those patients who were
anti-DNA antibody positive. ACL or anti-b2GPI antibody titres
did not change during the trial. There have been no serious
adverse events attributable to the study medication.
Conclusion We are successfully using a “rare disease study”
approach to conduct the first trial of a biologic therapy to
prevent pregnancy complications in women with APS and
LAC. Certolizumab appears to be safe in this small trial. Cer-
tolizumab appears to be safe so far in this small trial.
IMPACT must be completed before we can draw any conclu-
sions about efficacy, and its results must be confirmed in a
future study.
Acknowledgements NIAMS, Lupus Research institute, Lupus
Foundation of America
ClinicalTrials. gov Identifier: NCT03152058
Lay Summary Pregnancies in patients with antiphospholipid
syndrome who have a lupus anticoagulant in their blood have
a high likelihood of ending in fetal death or very premature
delivery because of poor placental development and pree-
clampsia. At present, there is no effective treatment for
women with these high-risk pregnancies, but our work in an
animal model that mimics this human condition shows that
blockade of TNF-a, a pivotal mediator of inflammation, pre-
vents adverse outcomes. Our study will determine whether
treatment during pregnancy with certolizumab, a TNF-ainhib-
itor that does not cross the placenta, reduces the rate of poor
pregnancy outcomes in women with clinical antiphospholipid
syndrome; and, if successful, it will provide a new approach
to protecting pregnancies in women with antiphospholipid
syndrome and a rationale for trials of TNF-ablockade in
women with other conditions, like SLE, who are at risk for
preeclampsia or placental insufficiency.
2022 Lupus 21
st
Century Encore
1202 VOCLOSPORIN FOR LUPUS NEPHRITIS: RESULTS OF THE
TWO-YEAR AURORA 2 CONTINUATION STUDY
1
Amit Saxena,
2
Onno Teng,
3
Chris Collins,
3
Nicole England,
3
Henry Leher.
1
NYU Langone
Hospital, Internal Medicine, New York, USA;
2
Leiden University Medical Center, Leiden,
Netherlands;
3
Aurinia Pharmaceuticals, Victoria, BC, Canada Presented by Henry Leher,
Aurinia Pharmaceuticals Inc., Victoria, BC, Canada
10.1136/lupus-2022-lupus21century.84
Background Voclosporin (VCS), a novel calcineurin inhibitor,
was approved in the US in January 2021 for the treatment of
adult patients with active lupus nephritis (LN) in combination
with background immunosuppressive therapy. The Phase 3
AURORA 1 study showed that the addition of VCS to myco-
phenolate mofetil (MMF) and low-dose steroids in patients
with LN significantly increased rates of complete renal
response at 52 weeks. Here we report the results of the com-
pleted continuation study, AURORA 2, which assessed the
long-term safety and tolerability of VCS compared to placebo
in patients with LN receiving treatment for an additional 24
months following completion of the AURORA 1 study.
Methods Key inclusion criteria for the parent AURORA 1
study included a diagnosis of biopsy-proven active LN (Class
III, IV, or V ± III/IV), proteinuria 1.5 mg/mg (2 mg/mg
for Class V) and estimated glomerular filtration rate (eGFR)
>45 mL/min/1.73 m
2
. Patients who completed AURORA 1
were eligible to enter AURORA 2 to continue on the same
blinded therapy as at the end of AURORA 1 (either VCS or
placebo twice daily in combination with MMF and low-dose
steroids). Safety and tolerability were monitored, and eGFR,
serum creatinine (SCr), and urine protein creatinine ratio
(UPCR) were also assessed.
Results In total, 116 and 100 patients in the VCS and control
arms enrolled in AURORA 2. There were no unexpected
safety signals in the VCS arm compared to control, with simi-
lar rates of serious adverse events reported in both arms (VCS
[18.1%] vs. control [23.0%]; table 1). Eight patients in each
arm experienced serious adverse events of infection; serious
coronavirus infections were observed in two patients in the
voclosporin arm and 5 patients in the control arm. There
were 4 and 2 adverse events by preferred term of renal
impairment reported in the VCS and control arms, respec-
tively, none of which were considered serious, and no reports
of acute kidney injury by preferred term in either arm. There
were no deaths in the VCS arm during AURORA 2; four
deaths were reported in the control arm (pulmonary embolism
[n=1], coronavirus infection [n=3]). Mean eGFR and SCr lev-
els remained stable through the end of AURORA 2. The dif-
ference between the VCS and control arms in LS mean
change from baseline in eGFR was 2.7 mL/min/1.73 m
2
at 4
weeks following study drug discontinuation (figure 1). The
mean reductions in UPCR observed in patients treated with
VCS in AURORA 1 were maintained in AURORA 2 with no
increase in UPCR noted at the follow-up visit 4 weeks after
study drug discontinuation.
Conclusion Voclosporin was well-tolerated over 3 years of
treatment with no unexpected safety signals detected. Further,
Abstracts
Lupus Science & Medicine 2022;9(Suppl 3):A1–A112 A85
on January 4, 2023 by guest. Protected by copyright.http://lupus.bmj.com/Lupus Sci Med: first published as 10.1136/lupus-2022-lupus21century.84 on 14 December 2022. Downloaded from
eGFR remained stable throughout the study period and the
significant and meaningful reductions in proteinuria achieved
in AURORA 1 were maintained. These data provide evidence
of a long-term treatment benefit of VCS in patients with LN.
Disclosures AS reports payments for Aurinia Pharmaceuticals
Inc. speaker bureaus; primary investigator for Aurinia Pharma-
ceuticals Inc. clinical trials; advisory fees from Eli Lilly, Astra-
Zeneca, GlaxoSmithKline and Kezar Life Sciences. YKOT
reports research grants from commercial organizations includ-
ing an unrestricted research grant from GlaxoSmithKline and
Aurinia Pharmaceuticals Inc.; primary investigator for Aurinia
Pharmaceuticals Inc. clinical trials; consultancy fees paid to
institution from Aurinia Pharmaceuticals Inc., Novartis, Glax-
oSmithKline, KezarBio, Vifor Pharma and Otsuka Pharmaceuti-
cals. CC, NE, and HL are employees and shareholders of
Aurinia Pharmaceuticals, Inc. HL is an employee and
shareholder of Aurinia Pharmaceuticals, Inc. Data first pre-
sented by Saxena A et al. at the EULAR Congress June 1-4,
2022. Editorial support provided by MediComm Partners Ltd.
Aurinia Pharmaceuticals Inc. provided funding for the study
and presentation.
1203 BLOCKADE OF THE MECHANISTIC TARGET OF
RAPAMYCIN ELICITS RAPID AND LASTING
IMPROVEMENT OF DISEASE ACTIVITY THROUGH
RESTRAINING PRO-INFLAMMATORY T CELL LINEAGE
SPECIFICATION IN PATIENTS WITH ACTIVE SLE
Zhi-Wei Lai, Ryan Kelly, Thomas Winans, Ivan Marchena, Ashwini Shadakshari, Julie Yu,
Maha Dawood, Ricardo Garcia, Hajra Tily, Lisa Francis, Stephen V Faraone, Paul E Phillips,
Andras Perl. Division of Rheumatology, Departments of Medicine, Microbiology and
Immunology, and Biochemistry and Molecular Biology, State University of New York,
Upstate Medical University, College of Medicine, Syracuse, New York 13210
10.1136/lupus-2022-lupus21century.85
Background Systemic lupus erythematosus (SLE) patients
exhibit proinflammatory lineage development in the immune
system that has been attributed to mechanistic target of rapa-
mycin (mTOR) activation. Moreover, mTOR activation has
also been shown in resident cells of tissues affected by end-
organ damage. Therefore, safety, tolerance, and efficacy of
rapamycin were examined in prospective
1
and retrospective
biomarker-driven clinical trials
2,3
.
Methods 40 patients having active disease and unresponsive or
intolerant to conventional medications were enrolled in a pro-
spective study
1
. Sirolimus was started at 2 mg/day with dos-
age adjusted to tolerance and 6-15 ng/ml trough levels.
Disease activity was evaluated by BILAG, SLEDAI, and predni-
sone use over 12 months. Blood samples of 56 matched
healthy subjects were obtained as controls for
Abstract 1202 Table 1 Overall Summary of Adverse Events
Control (n=100) Voclosporin (n=116)
n (%) n (%)
Any AE 80 (80.0) 100 (86.2)
Treatment-related AE 21 (21.0) 28 (24.1)
Serious AE 23 (23.0) 21 (18.1)
Serious Treatment-related AE 2 (2.0) 1 (0.9)
AE Leading to Study Drug Discontinuation 17 (17.0) 11 (9.5)
Death
*
4 (4.0) 0
Treatment-related Death 0 0
*
The four deaths in the control arm were due to pulmonary embolism (n=1) and coronavi-
rus infection (n=3). Includes adverse events starting on or after the first dose of study drug
in AURORA 2 up to 30 days after the last dose and all events of death reported during
study follow-up. Adverse events were aggregated by System Organ Class and Preferred
Term and coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 20.0.
AE, adverse event.
Abstract 1202 Figure 1 LS Mean eGFR over Time. Analysis of AURORA 2 patients includes data from pre-treatment baseline of AURORA 1, 12
months in AURORA 1 and up to 25 months in AURORA 2 (including 4- week post-treatment visit). Renal function assessed with corrected eGFR
(Chronic Kidney Disease Epidemiology Collaboration equation) using a prespecified ceiling of 90 mL/min/1.73 m2. Cl, confidence interval; eGFR,
estimated glomerular filtration rate; FUP, follow-up visit (4-week post-treatment visit); LS Mean, least squares mean.
Abstracts
A86 Lupus Science & Medicine 2022;9(Suppl 3):A1–A112
on January 4, 2023 by guest. Protected by copyright.http://lupus.bmj.com/Lupus Sci Med: first published as 10.1136/lupus-2022-lupus21century.84 on 14 December 2022. Downloaded from
