Inclusion Criteria. Participants must meet all of the following criteria to be eligible for randomization as
study participants.
1. Aged ≥ 18 and ≤ 60 years at the time of informed consent.
2. Meets EULAR/ACR 2019 criteria for SLE.
3. Moderately severe, active, but non-organ threatening disease. Specifically, signs or
symptoms meeting criteria for a minimum of:
1. 1 BILAG A (severe) score in the constitutional, musculoskeletal or mucocutaneous
system at the time of screening. See Exclusion Criteria number 2 for additional
detail.
2. 2 BILAG B (moderate) activity scores in any organ systems; or. 3. 1 BILAG B (moderate) activity score in any organ systems and a SELENA-SLEDAI
score of ≥ 6.
- - If there is only 1 BILAG B score:
- If a musculoskeletal BILAG B is scored due to moderate arthritis, where
some loss off functional range of movements was present on several days
over the last 4 weeks, there must also be a minimum of at least 3
joints that are both tender and swollen due to lupus disease activity
in wrists, MCPs or PIPs for the participant to qualify.
- - If a mucocutaneous BILAG B is scored due to acute or subacute cutaneous
skin eruption, the rash must cover at least 4% of the body surface area
for the participant to qualify.
Any active discoid lesion or other form
of chronic cutaneous lupus would be qualifying.
4. Approval, by an adjudication committee of a brief entry packet describing the type,
severity and duration of symptoms meeting the minimal criteria for entry. The
participant will meet this criterion if the committee is confident of all of the
following:
1. Convincing diagnosis of SLE,
2. Active disease, due to SLE, warranting the potential of dual therapy with potent
immune modulators,
3. No medical or other condition to contraindicate participation in a
placebo-controlled, outpatient study of this design.
5. Women of childbearing potential must have a negative serum pregnancy test at
screening.
6. Able or willing to use reliable methods of contraception, as outlined in the
Mycophenolate REMS brochure for health care providers, from 4 weeks prior to first
randomization to 6 weeks after completion of the study. This criterion applies to
females of reproductive potential.
Inclusion Criteria Required Prior to Randomization. Participants who meet the following criterion at the Stage 2 Randomization Visit may
proceed to randomization in Stage 2:
7. After completion of corticosteroid injection(s) and prior to randomization in Stage 2,
the participant and his/her physician must agree that disease activity has improved
sufficiently from screening such that randomization is acceptable.
1. The physician must score the CGI-C as "moderately better" or "much better" prior
to randomization.
• The reference value for the CGI-C should be the investigator's determination of
the participant's condition at the Screening Visit.
2. The participant must agree that his/her symptoms have improved (yes/no).
Exclusion Criteria. Participants who meet any of the following criteria are not eligible for randomization as
study participants:
1. Inability or unwillingness of a participant to understand and provide written informed
consent or comply with the study protocol.
2. BILAG A (severe) disease in the Cardiorespiratory, Neuropsychiatric, Gastrointestinal,
Ophthalmic, Renal, or Hematological Systems.
3. Severe or unstable nephritis defined as any of the following:
1. History of confirmed Class 3-5 nephritis within the last 2 years,
2. History of confirmed Class 3-5 nephritis > 2 years ago in the absence of
documented treatment including both induction and maintenance therapy,
3. UPCR > 1 g/g at screening, • If UPCR is > 0.5 g/g and ≤ 1 g/g at screening, then
a second assessment must be completed with at least 1 week between assessments.
If the second assessment is > 1 g/g or has increased by ≥ 0.3 g/g, then the
participant is excluded.
4. Evidence of chronic kidney disease defined as eGFR < 45 mL/min per 1.73 m2 at
screening, where 175 x (Creatinine/88.4)-1.154 x (Age)-0.203 x (0.742 if female) x
(1.212 if of African descent).
5. History of cirrhosis or chronic liver disease unrelated to SLE other than fatty liver
disease.
6. History, within 1 year of the Screening Visit, of uncontrolled SLE that would have
warranted a BILAG A (except mucocutaneous, constitutional, musculoskeletal) including,
but not limited to, hemolytic anemia, neuropsychiatric lupus, or interstitial lung
disease.
7. Uncontrolled HTN at the Screening or Randomization Visits defined as a blood pressure
> 150/100 with or without treatment, not to exceed 3 complementary antihypertensive
treatments.
8. Any of the following laboratory values during screening:
1. Hemoglobin (Hg) < 8.0 g/dL,
2. WBC < 2.0 x 10^9 cells/L,
3. ANC < 1.0 x 10^9 cells/L,
4. Platelets < 60 x 10^9 cells/L at screening,
• If platelets < 70 x 10^9 cells/L at screening, platelet count should be
retested 2 weeks later. If platelets are < 60 x 10^9 cells/L at retest,
participant will be excluded. 5. AST or ALT > 2.5 times the ULN,
6. Serum IgG levels < 5 g/L. 9. Use of ≥ 40 mg/day of prednisone within 4 weeks prior to the Screening Visit or use of
> 20 mg/day of prednisone at screening.
10. Unwilling or unable to taper to ≤ 10 mg/day of prednisone or equivalent by the day of
randomization.
11. Use of hydroxychloroquine, chloroquine, or quinacrine, if taking, at a prescribed dose
that has not been stable for at least 2 months prior to randomization.
12. Use of MMF within 1 year of randomization.
13. Use of CNIs within 3 months of randomization. Topical formulations applied stably for
at least one month are allowed.
14. Use of rituximab, obinutuzumab, ocrelizumab, or long-acting B cell depletion agents
within 1 year of randomization. Use of agents ≥ 6 months and within 1 year of
randomization is permitted if there is evidence of B cell reconstitution as defined as
CD19+ counts of ≥ 50 cells/µL.
15. History of intolerance or allergy to MMF, voclosporin, or long-acting corticosteroid
preparations.
16. Individuals with known hypersensitivity to Polysorbate 80 (Tween).
17. A woman who is pregnant, breastfeeding, or planning pregnancy from the time of consent
until 6 weeks after completion of the study.
18. Any participant with plans for major surgery during the time of the trial.
19. Active infections requiring hospitalization or intravenous antibiotics within 1 month
prior to the Screening Visit.
20. Any grade 2 infection or higher from 14 days prior to the Screening Visit and through
the screening period that has not resolved by randomization.
21. Acute herpes zoster within 4 months of the Screening Visit.
22. Positive results from a SARS-CoV-2 antigen test administered 2 days prior to and on
the day of first randomization.
23. Positive Quantiferon Gold (or equivalent) assay. Indeterminate Quantiferon Gold (or
equivalent) assays must be repeated (with same or other interferon gamma release assay
per local policy) and shown to be negative. Alternatively, if the Quantiferon Gold (or
equivalent) assay remains indeterminate, a participant must have a negative PPD.
Finally, if the participant has had the BCG vaccine or has some other condition
complicating the interpretation of TB testing, consultation with infection disease
specialist must be obtained.
• Participants diagnosed with latent TB are eligible but must have received
appropriate prophylaxis for 30 days prior to initiation of Stage 2 treatment.
24. Serologic evidence at screening of chronic infections including:
1. HIV infection.
2. Hepatitis B as indicated by surface antigen or hepatitis B core antibody
positivity; if a participant has an isolated positive hepatitis B core antibody,
they will be eligible to participate in the study if they are negative for reflex
viral load at Screening.
3. Hepatitis C as indicated by anti-hepatitis C antibody positivity; if a
participant is Hepatitis C antibody positive, they will be eligible to
participate in the study if they are negative for viral load at Screening.
25. Current, diagnosed, or self-reported drug or alcohol abuse within the last 6 months
that, in the opinion of the investigator, would interfere with the ability to comply
with study protocol.
26. Recipient of live attenuated vaccine(s) within 8 weeks of the Screening Visit.
27. Use of investigational drugs (excluding SARS-CoV-2 vaccinations or SARS-CoV2
therapeutics) within 8 weeks of the Screening Visit or 5 half-lives, whichever is
longer.
28. Past or current mental or physical problems or findings from physical examination or
laboratory testing that are not listed above, which, in the opinion of the
investigator, may pose additional risks from participation in the study, may interfere
with the participant's ability to comply with study requirements, or may impact the
quality or interpretation of the data obtained from the study.
