Systemic Lupus ErythematosusPhase 2DIVERTNCT05306873
Examining Distinct Immunophenotypes to Validate and Enhance Rational Treatment in Systemic Lupus
A Phase 2 study testing Mycophenolate Mofetil and Voclosporin in people with Systemic Lupus Erythematosus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 sites in United States.
Trial summary
The primary purpose of this study is to evaluate the potential effectiveness of 24 weeks of MMF within previously discovered immunologically defined subsets of SLE patients. Treatment effects will be evaluated within the individual immunologically-homogenous subsets defined at screening. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- Mycophenolate Mofetil and Voclosporin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 10 sitesUnited States
- Study dates
- 30 Nov 2022to 11 Jul 2024
- Phase
- Phase 2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Participants must meet all of the following criteria to be eligible for randomization as study participants.
- Aged ≥ 18 and ≤ 60 years at the time of informed consent.
- Meets EULAR/ACR 2019 criteria for SLE.
- Moderately severe, active, but non-organ threatening disease. Specifically, signs or symptoms meeting criteria for a minimum of:
- 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 BILAG B (moderate) activity scores in any organ systems; or
Show all 21Show fewer
- 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.
- 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:
- Convincing diagnosis of SLE,
- Active disease, due to SLE, warranting the potential of dual therapy with potent immune modulators,
- No medical or other condition to contraindicate participation in a placebo-controlled, outpatient study of this design.
- Women of childbearing potential must have a negative serum pregnancy test at screening.
- 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.
- Participants who meet the following criterion at the Stage 2 Randomization Visit may proceed to randomization in Stage 2:
- 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.
- 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.
- The participant must agree that his/her symptoms have improved (yes/no).
Who cannot join
- Participants who meet any of the following criteria are not eligible for randomization as study participants:
- Inability or unwillingness of a participant to understand and provide written informed consent or comply with the study protocol.
- BILAG A (severe) disease in the Cardiorespiratory, Neuropsychiatric, Gastrointestinal, Ophthalmic, Renal, or Hematological Systems.
- Severe or unstable nephritis defined as any of the following:
- History of confirmed Class 3-5 nephritis within the last 2 years,
- History of confirmed Class 3-5 nephritis > 2 years ago in the absence of documented treatment including both induction and maintenance therapy,
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- 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.
- 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).
- History of cirrhosis or chronic liver disease unrelated to SLE other than fatty liver disease.
- 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.
- 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.
- Any of the following laboratory values during screening:
- Hemoglobin (Hg) < 8.0 g/dL,
- WBC < 2.0 x 10^9 cells/L,
- ANC < 1.0 x 10^9 cells/L,
- 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
- AST or ALT > 2.5 times the ULN,
- Serum IgG levels < 5 g/L
- 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.
- Unwilling or unable to taper to ≤ 10 mg/day of prednisone or equivalent by the day of randomization.
- 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.
- Use of MMF within 1 year of randomization.
- Use of CNIs within 3 months of randomization. Topical formulations applied stably for at least one month are allowed.
- 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.
- History of intolerance or allergy to MMF, voclosporin, or long-acting corticosteroid preparations.
- Individuals with known hypersensitivity to Polysorbate 80 (Tween).
- A woman who is pregnant, breastfeeding, or planning pregnancy from the time of consent until 6 weeks after completion of the study.
- Any participant with plans for major surgery during the time of the trial.
- Active infections requiring hospitalization or intravenous antibiotics within 1 month prior to the Screening Visit.
- 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.
- Acute herpes zoster within 4 months of the Screening Visit.
- Positive results from a SARS-CoV-2 antigen test administered 2 days prior to and on the day of first randomization.
- 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.
- Serologic evidence at screening of chronic infections including:
- HIV infection.
- 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.
- 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.
- 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.
- Recipient of live attenuated vaccine(s) within 8 weeks of the Screening Visit.
- 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.
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Emory University School of Medicine: Division of Rheumatology
Atlanta, Georgia, 30307
Piedmont Healthcare: Rheumatology Atlanta
Atlanta, Georgia, 30318
Massachusetts General Hospital: Rheumatology, Allergy and Immunology, Center for Immunology and Inflammatory Diseases
Boston, Massachusetts, 02114
University of North Carolina at Chapel Hill; Thurston Arthritis Research Center: Division of Rheumatology, Allergy, and Immunology
Chapel Hill, North Carolina, 27599
PennState Health Milton S. Hershey Medical Center: Division of Rheumatology
Hershey, Pennsylvania, 17033
UCLA Medical Center: Division of Rheumatology
Los Angeles, California, 90095
Feinstein Institute for Medical Research: Center for Autoimmune and Musculoskeletal Diseases
Manhasset, New York, 11030
Yale University School of Medicine: Rheumatology, Allergy & Immunology
New Haven, Connecticut, 06519
Columbia University Medical Center: Department of Medicine, Division of Rheumatology
New York, New York, 10032
Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program
Oklahoma City, Oklahoma, 73104
About this study
Official title: A Phase 2, Double-Blind, Placebo-Controlled Trial of Mycophenolate Mofetil Alone or With Voclosporin for Systemic Lupus: Examining Distinct Immunophenotypes to Validate and Enhance Rational Treatment (DIVERT) (ALE10)
The primary purpose of this study is to evaluate the potential effectiveness of 24 weeks of MMF within previously discovered immunologically defined subsets of SLE patients. Treatment effects will be evaluated within the individual immunologically-homogenous subsets defined at screening. This study will also explore and compare pre-randomization gene expression patterns among responders and non-responders to MMF and MMF plus voclosporin, use comprehensive immunophenotyping to study the immunologic changes that accompany treatment- induced disease improvement and to better understand immunologic changes associated with the loss of clinical response.
Read the detailed description
The study was conducted in 3 stages with a maximum participant follow-up time of 56 weeks. Stage 1 was a treatment withdrawal period lasting up to 4 weeks where consenting participants receive up to 3 intramuscular injections of a long-acting corticosteroid to achieve amelioration of symptoms. In addition, participants withdraw from all other treatments for lupus with the following exceptions:
(i) as needed (PRN) nonsteroidal anti-inflammatory treatments may be started or continued, (ii) PRN topicals may be continued, (iii) hydroxychloroquine, chloroquine, or quinacrine may be continued at any stable dose, and (iv) prednisone, if<= 10 mg/day, may be continued at stable doses but not started.
Qualifying participants from Stage 1 were randomized (1:1) into Stage 2 to receive either MMF or placebo for MMF for up to 48 weeks. Participants who experienced a Stage 2 treatment failure at or before the Week 24 visit and a corticosteroid injection was deemed sufficient for treatment without new or increased lupus medication were eligible to re-randomize (1:1) into Stage 3 to receive either MMF + Voclosporin or MMF + Placebo for Voclosporin for up to 24 Weeks.
Participants who did not experience a Stage 2 treatment failure at or before the Stage 2 Week 48 visit were to return for an End of Study/Safety Follow-up visit 4 weeks after the final dose of study-provided medication. Similarly, participants who did not experience a Stage 3 treatment failure at or before the Stage 3 Week 24 visits were asked to return for an End of Study/Safety Follow-up visit 4 weeks after the final dose of study provided medication.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- Mycophenolate Mofetil, Placebo for Mycophenolate Mofetil, Voclosporin, Placebo for Voclosporin
- Keywords
- Systemic Lupus, Mycophenolate Mofetil, Voclosporin
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called CellCept, MMF
Stage 2 Dosing:
Week 1: Participants will receive 500mg MMF/Placebo twice daily
Week 2: Participants will receive 500mg/Placebo in the morning and 1,000mg MMF/Placebo in the evening
Weeks 3-48: Participants will receive 1000mg MMF/Placebo twice daily
Placebo for Mycophenolate MofetilDrug
Also called CellCept, MMF
Stage 2 Dosing:
Week 1: Participants will receive 500mg MMF/Placebo twice daily Week 2: Participants will receive 500mg/Placebo in the morning and 1,000mg MMF/Placebo in the evening Weeks 3-48: Participants will receive 1000mg MMF/Placebo twice daily
VoclosporinDrug
Also called Lupkynis, Lupkynis(TM)
Weeks 1-24: 23.7 mg Voclosporin (3 x 7.9 capsules) twice daily
Placebo for VoclosporinDrug
Weeks 1-24: 23.7 mg Placebo for Voclosporin (3 x 7.9 capsules) twice daily
Also called CellCept, MMF
Stage 3 Dosing:
Participants who received placebo MMF in Stage 2:
- Week 1: Participants will receive 500mg MMF plus matching placebo for MMF (to appear like a 1000mg dose) twice daily
- Week 2: Participants will receive 500mg plus matching placebo for MMF (to appear like a 1000mg dose) and 1000mg in divided doses
- Weeks 3-24: 1000mg MMF twice daily
Participants who received MMF in Stage 2
- Week 1-24: 1000mg MMF twice daily
| Study group | Role | What they receive |
|---|---|---|
| MMF | Experimental | Participants will receive 500 mg mycophenolate mofetil (MMF) bid for 7 days, followed by 500mg and 1,000mg MMF in divided doses for 7 days. They will then continue at a stable dose of 1,000mg MMF bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization Receives: Drug: Mycophenolate Mofetil |
| Placebo for MMF | Placebo comparator | Participants will receive 500 mg corresponding mycophenolate mofetil (MMF) placebo bid for 7 days, followed by 500mg and 1,000mg corresponding MMF placebo in divided doses for 7 days. They will then continue at a stable dose of 1,000mg corresponding MMF placebo bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization Receives: Drug: Placebo for Mycophenolate Mofetil |
| MMF+ Placebo for Voclosporin | Experimental | Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus placebo for voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication Receives: Drug: Placebo for Voclosporin; Drug: Mycophenolate Mofetil |
| MMF+ Voclosporin | Experimental | Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication Receives: Drug: Voclosporin; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Participants Who Experience a Stage 2 Treatment Failure at or Before the Stage 2 Week 24 Visit.
Treatment failure is defined as the first occurrence after randomization (Stage 2) of any of the following events:
- Methylprednisolone acetate injection or treatment with a new or increased lupus medication, except the occasional use of corticosteroids for reasons not associated with Systemic Lupus Erythematosus (SLE) flare
- British Isles Lupus Assessment Group (BILAG) flare, defined as any item marked new or worse that could support a BILAG A (severe flare) or 2 organs with items marked new or worse that could support a BILAG B (moderate flare), and if the participant's condition is deemed by the investigator to be "moderately worse" or "much worse" compared to the day of randomization, as assessed by the Clinician Global Impression of Change (CGI-C)
- Premature permanent discontinuation of study-assigned treatment for any reason
Measured: From Baseline to Stage 2 Week 24
Secondary outcomes (15)
Clinical Response in Stage 2, Defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 2 Week 24.
The BILAG-based Composite Lupus Assessment (BICLA) is a composite index used to assess disease activity in SLE. A BICLA response is defined as meeting all of the following criteria:
- Improvement of all Screening BILAG A scores to B, C or D
- Improvement of all Screening BILAG B scores to C or D
- No new BILAG A score among organs scored as B, C, D, or E at Screening
- <= 1 new BILAG B score among organs scored as C, D, or E at Screening
- No worsening of the Hybrid Systemic Lupus Erythematosus Disease Activity Index (H-SLEDAI)
- Less than a 10% increase (worsening) in the Physician's Global Assessment (PGA)
Participants who experience treatment failure prior to Stage 2 Week 24 visit are imputed as BICLA Non-responders at Stage 2 Week 24. Participants who do not have evaluable data at Stage 2 Week 24 for reasons other than a treatment failure are not imputed.
Measured: Stage 2 Week 24
The Proportion of Participants Who Experience a Stage 3 Treatment Failure, After Stage 3 Re-randomization at or Before Completing Stage 3 Week 24.
Treatment failure is defined as the first occurrence after re-randomization (Stage 3) of any of the following events:
- Methylprednisolone acetate injection or treatment with a new or increased lupus medication, except the occasional use of corticosteroids for reasons not associated with Systemic Lupus Erythematosus (SLE) flare
- British Isles Lupus Assessment Group (BILAG) flare, defined as any item marked new or worse that could support a BILAG A (severe flare) or 2 organs with items marked new or worse that could support a BILAG B (moderate flare), and if the participant's condition is deemed by the investigator to be "moderately worse" or "much worse" compared to the day of randomization, as assessed by the Clinician Global Impression of Change (CGI-C)
- Premature permanent discontinuation of study-assigned treatment for any reason
Measured: From re-randomization to Stage 3 Week 24
Time to Treatment Failure in Stage 3, Defined as the Interval From the Day of Stage 3 Randomization Until the Day of Treatment Failure.
Treatment failure is defined as the first occurrence after re-randomization (Stage 3) of any of the following events:
- Methylprednisolone acetate injection or treatment with a new or increased lupus medication, except the occasional use of corticosteroids for reasons not associated with Systemic Lupus Erythematosus (SLE) flare
- British Isles Lupus Assessment Group (BILAG) flare, defined as any item marked new or worse that could support a BILAG A (severe flare) or 2 organs with items marked new or worse that could support a BILAG B (moderate flare), and if the participant's condition is deemed by the investigator to be "moderately worse" or "much worse" compared to the day of randomization, as assessed by the Clinician Global Impression of Change (CGI-C)
- Premature permanent discontinuation of study-assigned treatment for any reason
Measured: Start of Stage 3 up to the day of treatment failure
Clinical Response in Stage 3, Defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 3 Week 24.
The BILAG-based Composite Lupus Assessment (BICLA) is a composite index used to assess disease activity in SLE. A BICLA response is defined as meeting all of the following criteria:
- Improvement of all Screening BILAG A scores to B, C or D
- Improvement of all Screening BILAG B scores to C or D
- No new BILAG A score among organs scored as B, C, D, or E at Screening
- <= 1 new BILAG B score among organs scored as C, D, or E at Screening
- No worsening of the Hybrid Systemic Lupus Erythematosus Disease Activity Index (H-SLEDAI)
- Less than a 10% increase (worsening) in the Physician's Global Assessment (PGA)
Participants who experience treatment failure prior to Stage 3 Week 24 visit are imputed as BICLA Non-responders at Stage 2 Week 24. Participants who do not have evaluable data at Stage 3 Week 24 for reasons other than a treatment failure are not imputed.
Measured: Stage 3 Week 24
The Incidence of Grade 3 or Higher Related Adverse Events (AEs) in Stage 2
Defined as adverse events that emerged during Stage 2 that are of Grade 3 or higher with a relationship to Stage 2 study drug of Possible or Definite.
Measured: Stage 2 Day 0 up to Stage 2 Week 48
The Incidence of Grade 3 or Higher Related Adverse Events (AEs) in Stage 3
Defined as adverse events that emerged during Stage 3 that are of Grade 3 or higher with a relationship to Stage 3 study drug of Possible or Definite.
Measured: After Stage 3 re-randomization Day 0 to Stage 3 Week 24
The Incidence of Grade 3 or Higher Infections in Stage 1
Defined as infection adverse events that emerged during Stage 1 and are of Grade 3 or higher.
Measured: Day -28 to Day -1
The Incidence of Grade 3 or Higher Infections in Stage 2
Defined as infection adverse events that emerged during Stage 2 and are of Grade 3 or higher.
Measured: Stage 2 Day 0 up to Stage 2 Week 48
The Incidence of Grade 3 or Higher Infections in Stage 3
Defined as infection adverse events that emerged during Stage 3 and are of Grade 3 or higher.
Measured: After Stage 3 re-randomization Day 0 to Stage 3 Week 24
The Incidence of Renal Dysfunction in Stage 1
Defined as Grade 3 or higher chronic kidney disease with eGFR < 30 ml/min per 1.73 m^2
Measured: Day -28 to Day -1
The Incidence of Renal Dysfunction in Stage 2
Defined as Grade 3 or higher chronic kidney disease with eGFR < 30 ml/min per 1.73 m^2
Measured: Stage 2 Day 0 up to Stage 2 Week 48
The Incidence of Renal Dysfunction in Stage 3
Defined as Grade 3 or higher chronic kidney disease with eGFR < 30 ml/min per 1.73 m^2
Measured: After Stage 3 re-randomization Day 0 to Stage 3 Week 24
The Incidence of Grade 3 or Higher Hypertension in Stage 1
Defined as a systolic blood pressure >= 160 mm Hg or a diastolic blood pressure of >= 100 mm Hg
Measured: Day -28 to Day -1
The Incidence of Grade 3 or Higher Hypertension in Stage 2
Defined as a systolic blood pressure >= 160 mm Hg or a diastolic blood pressure of >= 100 mm Hg
Measured: Stage 2 Day 0 up to Stage 2 Week 48
The Incidence of Grade 3 or Higher Hypertension in Stage 3
Defined as a systolic blood pressure >= 160 mm Hg or a diastolic blood pressure of >= 100 mm Hg
Measured: After Stage 3 re-randomization Day 0 to Stage 3 Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2022
- Study start30 Nov 2022
- Primary completion13 Jun 2024
- Study completion11 Jul 2024
Why it stopped: The study was closed due to slow enrollment.
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.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Joan Merrill, M.D., Study chair, Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05306873
- Sponsor's protocol ID
- DAIT ALE10
- Acronym
- DIVERT
- Status last verified
- Sep 2025
- First submitted
- 11 Mar 2022
- Last updated
- 9 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Placebo-Controlled Trial of Mycophenolate Mofetil Alone or With Voclosporin for Systemic Lupus: Examining Distinct Immunophenotypes to Validate and Enhance Rational Treatment (DIVERT) (ALE10)
- ClinicalTrials.gov ID
- NCT05306873
- Acronym / sponsor ID
- DIVERT / DAIT ALE10
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Systemic Lupus, Mycophenolate Mofetil, Voclosporin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was closed due to slow enrollment.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 30 Nov 2022 (actual)
- Primary completion
- 13 Jun 2024 (actual)
- Study completion
- 11 Jul 2024 (actual)
- First posted
- 1 Apr 2022 (actual)
- Results
- Posted 9 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to evaluate the potential effectiveness of 24 weeks of MMF within previously discovered immunologically defined subsets of SLE patients. Treatment effects will be evaluated within the individual immunologically-homogenous subsets defined at screening. This study will also explore and compare pre-randomization gene expression patterns among responders and non-responders to MMF and MMF plus voclosporin, use comprehensive immunophenotyping to study the immunologic changes that accompany treatment- induced disease improvement and to better understand immunologic changes associated with the loss of clinical response.
Detailed description
The study was conducted in 3 stages with a maximum participant follow-up time of 56 weeks. Stage 1 was a treatment withdrawal period lasting up to 4 weeks where consenting participants receive up to 3 intramuscular injections of a long-acting corticosteroid to achieve amelioration of symptoms. In addition, participants withdraw from all other treatments for lupus with the following exceptions:
(i) as needed (PRN) nonsteroidal anti-inflammatory treatments may be started or continued, (ii) PRN topicals may be continued, (iii) hydroxychloroquine, chloroquine, or quinacrine may be continued at any stable dose, and (iv) prednisone, if<= 10 mg/day, may be continued at stable doses but not started.
Qualifying participants from Stage 1 were randomized (1:1) into Stage 2 to receive either MMF or placebo for MMF for up to 48 weeks. Participants who experienced a Stage 2 treatment failure at or before the Week 24 visit and a corticosteroid injection was deemed sufficient for treatment without new or increased lupus medication were eligible to re-randomize (1:1) into Stage 3 to receive either MMF + Voclosporin or MMF + Placebo for Voclosporin for up to 24 Weeks.
Participants who did not experience a Stage 2 treatment failure at or before the Stage 2 Week 48 visit were to return for an End of Study/Safety Follow-up visit 4 weeks after the final dose of study-provided medication. Similarly, participants who did not experience a Stage 3 treatment failure at or before the Stage 3 Week 24 visits were asked to return for an End of Study/Safety Follow-up visit 4 weeks after the final dose of study provided medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MMF | Experimental | Drug: Mycophenolate MofetilParticipants will receive 500 mg mycophenolate mofetil (MMF) bid for 7 days, followed by 500mg and 1,000mg MMF in divided doses for 7 days. They will then continue at a stable dose of 1,000mg MMF bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization |
| Placebo for MMF | Placebo comparator | Drug: Placebo for Mycophenolate MofetilParticipants will receive 500 mg corresponding mycophenolate mofetil (MMF) placebo bid for 7 days, followed by 500mg and 1,000mg corresponding MMF placebo in divided doses for 7 days. They will then continue at a stable dose of 1,000mg corresponding MMF placebo bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization |
| MMF+ Placebo for Voclosporin | Experimental | Drug: Placebo for Voclosporin, Drug: Mycophenolate MofetilParticipants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus placebo for voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication |
| MMF+ Voclosporin | Experimental | Drug: Voclosporin, Drug: Mycophenolate MofetilParticipants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (21 listed)
- Participants must meet all of the following criteria to be eligible for randomization as study participants.
- Aged ≥ 18 and ≤ 60 years at the time of informed consent.
- Meets EULAR/ACR 2019 criteria for SLE.
- Moderately severe, active, but non-organ threatening disease. Specifically, signs or symptoms meeting criteria for a minimum of:
- 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:
Key exclusion criteria (43 listed)
- Participants who meet any of the following criteria are not eligible for randomization as study participants:
- Inability or unwillingness of a participant to understand and provide written informed consent or comply with the study protocol.
- BILAG A (severe) disease in the Cardiorespiratory, Neuropsychiatric, Gastrointestinal, Ophthalmic, Renal, or Hematological Systems.
- Severe or unstable nephritis defined as any of the following:
- 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).
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 |
|---|---|---|
| Mycophenolate MofetilAlso: CellCept, MMFStage 2 Dosing: Week 1: Participants will receive 500mg MMF/Placebo twice daily Week 2: Participants will receive 500mg/Placebo in the morning and 1,000mg MMF/Placebo in the evening Weeks 3-48: Participants will receive 1000mg MMF/Placebo twice daily | Drug | MMF |
| Placebo for Mycophenolate MofetilAlso: CellCept, MMFStage 2 Dosing: Week 1: Participants will receive 500mg MMF/Placebo twice daily Week 2: Participants will receive 500mg/Placebo in the morning and 1,000mg MMF/Placebo in the evening Weeks 3-48: Participants will receive 1000mg MMF/Placebo twice daily | Drug | Placebo for MMF |
| VoclosporinAlso: Lupkynis, Lupkynis(TM)Weeks 1-24: 23.7 mg Voclosporin (3 x 7.9 capsules) twice daily | Drug | MMF+ Voclosporin |
| Placebo for VoclosporinWeeks 1-24: 23.7 mg Placebo for Voclosporin (3 x 7.9 capsules) twice daily | Drug | MMF+ Placebo for Voclosporin |
| Mycophenolate MofetilAlso: CellCept, MMFStage 3 Dosing: Participants who received placebo MMF in Stage 2: * Week 1: Participants will receive 500mg MMF plus matching placebo for MMF (to appear like a 1000mg dose) twice daily * Week 2: Participants will receive 500mg plus matching placebo for MMF (to appear like a 1000mg dose) and 1000mg in divided doses * Weeks 3-24: 1000mg MMF twice daily Participants who received MMF in Stage 2 • Week 1-24: 1000mg MMF twice daily | Drug | MMF+ Placebo for Voclosporin, MMF+ Voclosporin |
Primary outcome
The Percentage of Participants Who Experience a Stage 2 Treatment Failure at or Before the Stage 2 Week 24 Visit.
Time frame: From Baseline to Stage 2 Week 24
Treatment failure is defined as the first occurrence after randomization (Stage 2) of any of the following events: 1. Methylprednisolone acetate injection or treatment with a new or increased lupus medication, except the occasional use of corticosteroids for reasons not associated with Systemic Lupus Erythematosus (SLE) flare 2. British Isles Lupus Assessment Group (BILAG) flare, defined as any item marked new or worse that could support a BILAG A (severe flare) or 2 organs with items marked new or worse that could support a BILAG B (moderate flare), and if the participant's condition is deemed by the investigator to be "moderately worse" or "much worse" compared to the day of randomization, as assessed by the Clinician Global Impression of Change (CGI-C) 3. Premature permanent discontinuation of study-assigned treatment for any reason
15 secondary outcomes
Clinical Response in Stage 2, Defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 2 Week 24.
Time frame: Stage 2 Week 24
The Proportion of Participants Who Experience a Stage 3 Treatment Failure, After Stage 3 Re-randomization at or Before Completing Stage 3 Week 24.
Time frame: From re-randomization to Stage 3 Week 24
Time to Treatment Failure in Stage 3, Defined as the Interval From the Day of Stage 3 Randomization Until the Day of Treatment Failure.
Time frame: Start of Stage 3 up to the day of treatment failure
Clinical Response in Stage 3, Defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 3 Week 24.
Time frame: Stage 3 Week 24
The Incidence of Grade 3 or Higher Related Adverse Events (AEs) in Stage 2
Time frame: Stage 2 Day 0 up to Stage 2 Week 48
The Incidence of Grade 3 or Higher Related Adverse Events (AEs) in Stage 3
Time frame: After Stage 3 re-randomization Day 0 to Stage 3 Week 24
The Incidence of Grade 3 or Higher Infections in Stage 1
Time frame: Day -28 to Day -1
The Incidence of Grade 3 or Higher Infections in Stage 2
Time frame: Stage 2 Day 0 up to Stage 2 Week 48
The Incidence of Grade 3 or Higher Infections in Stage 3
Time frame: After Stage 3 re-randomization Day 0 to Stage 3 Week 24
The Incidence of Renal Dysfunction in Stage 1
Time frame: Day -28 to Day -1
The Incidence of Renal Dysfunction in Stage 2
Time frame: Stage 2 Day 0 up to Stage 2 Week 48
The Incidence of Renal Dysfunction in Stage 3
Time frame: After Stage 3 re-randomization Day 0 to Stage 3 Week 24
The Incidence of Grade 3 or Higher Hypertension in Stage 1
Time frame: Day -28 to Day -1
The Incidence of Grade 3 or Higher Hypertension in Stage 2
Time frame: Stage 2 Day 0 up to Stage 2 Week 48
The Incidence of Grade 3 or Higher Hypertension in Stage 3
Time frame: After Stage 3 re-randomization Day 0 to Stage 3 Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Autoimmunity Centers of ExcellenceLink provided by the sponsor.
- National Institute of Allergy and Infectious DiseasesLink provided by the sponsor.
- Division of Allergy, Immunology, and TransplantationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
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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.
Joan Merrill, M.D. study chair
Oklahoma Medical Research Foundation: Arthritis and Clinical Immunology Research Program
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycophenolate Mofetil and Voclosporin in people with Systemic Lupus Erythematosus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 10 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 21 inclusion and 43 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: stopped early, as of the sponsor's last update on 9 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 9 Sep 2025). 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?
The Percentage of Participants Who Experience a Stage 2 Treatment Failure at or Before the Stage 2 Week 24 Visit. (time frame: From Baseline to Stage 2 Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Sep 2025.