Trial Outcomes & Findings for Randomized MMF Withdrawal in Systemic Lupus Erythematosus (SLE) (NCT NCT01946880)

NCT ID: NCT01946880

Last Updated: 2020-08-17

Results Overview

Disease reactivation requires:1) SELENA-SLEDAI mild/moderate or severe flare,and 2) Increased immunosuppressive therapy on a sustained basis,defined by one of the following criteria:a) Sustained activity:Significant prolonged SLE flare requiring steroid increase/burst to ≥15 mg/day prednisone (or equivalent) for \>4 weeks.b) Frequent relapsing/remitting:Participant flares requiring an increase/burst of steroids and is successfully tapered to \<15 mg/day within 4 weeks, but this occurs on \>2 occasions, or IA, IM or IV steroids on more than1 occasion.c)Clinical activity of sufficient severity to warrant resumption of/increased dose of MMF or addition of other major immunosuppressive including AZA or MTX.Regardless of steroid use, if the investigator observes disease activity of sufficient severity to warrant resumption, addition or increase in dosage of major immunosuppressant in the setting of a SELENA-SLEDAI flare, participant has met the primary endpoint.Risk difference also included

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 102 participants
• Primary outcome timeframe: Baseline (Treatment Randomization) to Week 60
• Results posted on: 2020-08-17

Participant Flow

Nineteen study sites in the US were activated. A total of 123 participants were screened and 102 were randomized from November 2013 to May 2018.

Participant milestones

Measure	MMF Maintenance Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).	MMF Withdrawal Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).
Overall Study STARTED	50	52
Overall Study COMPLETED	43	49
Overall Study NOT COMPLETED	7	3

Reasons for withdrawal

Measure	MMF Maintenance Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).	MMF Withdrawal Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	1	1
Overall Study Withdrawal by Subject	3	2
Overall Study Met Primary Endpoint	1	0
Overall Study Personal and Family Issues	1	0

Baseline Characteristics

Randomized MMF Withdrawal in Systemic Lupus Erythematosus (SLE)

Baseline characteristics by cohort

Measure	Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).	Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	Total n=102 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	48 Participants n=5 Participants	50 Participants n=7 Participants	98 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Continuous	42.4 years STANDARD_DEVIATION 12.9 • n=5 Participants	41.6 years STANDARD_DEVIATION 12.5 • n=7 Participants	42.0 years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	47 Participants n=7 Participants	86 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants	40 Participants n=7 Participants	80 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	17 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	50 Participants n=5 Participants	52 Participants n=7 Participants	102 Participants n=5 Participants
Disease Manifestation: Renal vs. Non-Renal Disease Renal Disease	40 Participants n=5 Participants	38 Participants n=7 Participants	78 Participants n=5 Participants
Disease Manifestation: Renal vs. Non-Renal Disease Non-Renal Disease	10 Participants n=5 Participants	14 Participants n=7 Participants	24 Participants n=5 Participants
Baseline MMF Dose < 2000 mg/day	26 Participants n=5 Participants	30 Participants n=7 Participants	56 Participants n=5 Participants
Baseline MMF Dose ≥ 2000 mg/day	24 Participants n=5 Participants	22 Participants n=7 Participants	46 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

Disease reactivation requires:1) SELENA-SLEDAI mild/moderate or severe flare,and 2) Increased immunosuppressive therapy on a sustained basis,defined by one of the following criteria:a) Sustained activity:Significant prolonged SLE flare requiring steroid increase/burst to ≥15 mg/day prednisone (or equivalent) for >4 weeks.b) Frequent relapsing/remitting:Participant flares requiring an increase/burst of steroids and is successfully tapered to <15 mg/day within 4 weeks, but this occurs on >2 occasions, or IA, IM or IV steroids on more than1 occasion.c)Clinical activity of sufficient severity to warrant resumption of/increased dose of MMF or addition of other major immunosuppressive including AZA or MTX.Regardless of steroid use, if the investigator observes disease activity of sufficient severity to warrant resumption, addition or increase in dosage of major immunosuppressant in the setting of a SELENA-SLEDAI flare, participant has met the primary endpoint.Risk difference also included

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing Clinically Significant Disease Reactivation by Week 60	9 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups they were randomized. Participants who met disease reactivation were analyzed.

The time to clinically significant disease reactivation was defined as the time from Baseline/Day 0 to the date of the first Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) assessment that met (or went on to meet) the criteria for clinically significant disease reactivation. Time to clinically significant disease reactivation was defined in study weeks as: date of SELENA-SLEDAI assessment that met reactivation criteria minus (-) baseline date.

Outcome measures

Measure	MMF Withdrawal n=9 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=5 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Time to Clinically Significant Disease Reactivation	38.5 Weeks Standard Deviation 19.6	38.0 Weeks Standard Deviation 18.7

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes mild/moderate or severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60	25 Participants	20 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Participants in the renal subgroup were analyzed.

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

Outcome measures

Measure	MMF Withdrawal n=37 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=39 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 Within the Lupus Nephritis Subgroup	19 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Participants in the non-renal subgroup were analyzed.

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

Outcome measures

Measure	MMF Withdrawal n=14 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=10 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 Within the Non-Lupus Nephritis Subgroup	6 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Baseline MMF \<2000 mg/day participants were analyzed.

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

MMF: mycophenolate mofetil

Outcome measures

Measure	MMF Withdrawal n=30 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=26 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 in the Baseline MMF<2000 mg/Day Subgroup	13 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Baseline MMF \>=2000 mg/day participants were analyzed

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

MMF: mycophenolate mofetil

Outcome measures

Measure	MMF Withdrawal n=21 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=23 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing a Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 in the Baseline MMF ≥ 2000 mg/Day Subgroup	12 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing a Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60	8 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Participants in the renal subgroup were analyzed.

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

Outcome measures

Measure	MMF Withdrawal n=37 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=39 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing a Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 Within the Lupus Nephritis Subgroup	7 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Participants in the non-renal subgroup were analyzed.

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

Outcome measures

Measure	MMF Withdrawal n=14 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=10 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing a Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 Within the Non-Lupus Nephritis Subgroup	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Baseline MMF \<2000 mg/day participants were analyzed.

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

MMF: mycophenolate mofetil

Outcome measures

Measure	MMF Withdrawal n=30 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=26 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 in the Baseline MMF <2000 mg/Day Subgroup	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Baseline MMF \>=2000 mg/day participants were analyzed

The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

MMF: mycophenolate mofetil

Outcome measures

Measure	MMF Withdrawal n=21 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=23 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare by Week 60 in the Baseline MMF ≥ 2000 mg/Day Subgroup	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups they were randomized. Participants who had SELENA-SLEDAI flares were analyzed.

The time to first mild/moderate or severe SELENA-SLEDAI flare was defined as the time from Baseline/Day 0 to the date of the first mild/moderate or severe SELENA-SLEDAI flare. Time to SELENA-SLEDAI flare was defined in study weeks as: date of SELENA-SLEDAI flare minus (-) baseline date. The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes mild/moderate or severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE.

Outcome measures

Measure	MMF Withdrawal n=25 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=20 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Time to First Mild/Moderate or Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare	27.5 Weeks Standard Deviation 16.7	20.5 Weeks Standard Deviation 19.5

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups they were randomized. Participants who had SELENA-SLEDAI flares were analyzed.

The time to first severe SELENA-SLEDAI flare was defined as the time from Baseline/Day 0 to the date of the first severe SELENA-SLEDAI flare. Time to severe SELENA-SLEDAI flare was defined in study weeks as: date of SELENA-SLEDAI flare minus (-) baseline date. The SELENA-SLEDAI assesses systemic lupus erythematosus (SLE) disease activity and categorizes mild/moderate or severe flares based on changes in the SLEDAI score, the Physician's Global Assessment (PGA), medication use (prednisone, Nonsteroidal anti-inflammatory drugs, Plaquenil, major immunosuppressives), other disease activity criteria, and hospitalization due to SLE.

Outcome measures

Measure	MMF Withdrawal n=8 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=4 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Time to First Severe Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus-Disease Activity Index (SELENA-SLEDAI) Flare	41.5 Weeks Standard Deviation 17.5	43.5 Weeks Standard Deviation 9.9

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

The BILAG assesses participants on a variety of disease activity criteria in nine body system categories (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological). Each category is scored as an A, B, C, or D/E, where A indicates most severe disease activity and D/E indicates inactive/no disease activity. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants Experiencing Any British Isles Lupus Assessment Group (BILAG) A Flare by Week 60	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the group they were randomized. Participants in the renal subgroup were analyzed.

The BILAG assesses participants on a variety of disease activity criteria in nine body system categories (constitutional, mucocutaneous, neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, and hematological). Each category is scored as an A, B, C, or D/E, where A indicates most severe disease activity and D/E indicates inactive/no disease activity. An estimate of the risk difference ((i.e. risk(MMF Withdrawal) - risk(MMF Maintenance) and its corresponding 95% confidence interval (CI) were also included.

Outcome measures

Measure	MMF Withdrawal n=37 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=39 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Participants in the Lupus Nephritis Subgroup Experiencing a British Isles Lupus Assessment Group (BILAG) A Renal Flare by Week 60	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

The SLICC/DI measures accumulated damage that has occurred since the onset of systemic lupus erythematosus (SLE), regardless of cause, in 12 organ systems. SLE damage is defined as an irreversible change in an organ or system that has been present for at least 6 months. The SLICC/DI includes 39 areas of damage in 12 domains, where each item is rated as present or absent; if evidence of damage is present for a particular item, it is given a score of 1. Some items are scored with 2 or 3 points in the case of recurring events or end stage renal disease. The SLICC/DI total score will be computed as the sum of all scores for items indicated as present; scores can range from 0 to 45. Higher scores indicate more damage.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Change From Baseline in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Disease Damage Index for Systemic Lupus Erythematosus (SLICC/DI): Total Score Week 24	0.0 Scores on a Scale Standard Deviation 0.15	0.0 Scores on a Scale Standard Deviation 0.15
Change From Baseline in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Disease Damage Index for Systemic Lupus Erythematosus (SLICC/DI): Total Score Week 48	0.0 Scores on a Scale Standard Deviation 0.15	0.0 Scores on a Scale Standard Deviation 0.22
Change From Baseline in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Disease Damage Index for Systemic Lupus Erythematosus (SLICC/DI): Total Score Week 60	0.0 Scores on a Scale Standard Deviation 0.21	0.0 Scores on a Scale Standard Deviation 0.37

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

The addition of aggressive adjunctive therapy could include intravenous (IV) immunoglobulin or rituximab at any point during the participant's study participation. A change in therapy to cytotoxic drug due to flare could include drugs such as cyclophosphamide, etc. A blinded list of study medications was reviewed to identify the addition of aggressive adjunctive therapy or cytotoxic drugs.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
The Addition of Aggressive Adjunctive Therapy to Mycophenolate Mofetil (MMF) or Change in MMF Therapy to Cytotoxic Drug Due to Flare by Week 60	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

Steroids include medications that code to a medication class which includes the terms "glucocorticoid" or "corticosteroid". Systemic steroids will include any of these steroids that are taken by mouth (PO), intravenous (IV), or intramuscular (IM). Total cumulative systemic steroid dose, in milligrams, was summarized over the 60 week study period, or until early study termination, for each participant.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Cumulative Systemic Steroid Dose by Week 60	912 steroid dose (mg) Standard Deviation 1995	851 steroid dose (mg) Standard Deviation 1148

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

FACIT-Fatigue scale (FS) is a 13-item questionnaire completed by the patient (participant), that provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-FS score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status. A decrease in the FACIT-FS score reflects worse fatigue/quality of life.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT-F) Fatigue Scale (FS): Total Score Week 24	-0.81 units on a scale Standard Deviation 10.62	-2.41 units on a scale Standard Deviation 8.13
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT-F) Fatigue Scale (FS): Total Score Week 48	-0.85 units on a scale Standard Deviation 9.75	-3.39 units on a scale Standard Deviation 7.53
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT-F) Fatigue Scale (FS): Total Score Week 60	0.42 units on a scale Standard Deviation 9.05	-3.13 units on a scale Standard Deviation 8.82

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

The SF-36 is a 36-item, patient-reported survey of patient health. Higher scores indicate better outcomes while lower scores indicate more disability. The PF score is used to assess changes in physical functioning. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 equivalent to no disability.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Change From Baseline in the Short Form Health Survey (SF-36) Physical Functioning (PF) Score Week 24	0.22 Scores on a Scale Standard Deviation 7.20	-0.33 Scores on a Scale Standard Deviation 4.05
Change From Baseline in the Short Form Health Survey (SF-36) Physical Functioning (PF) Score Week 48	0.95 Scores on a Scale Standard Deviation 6.13	-0.49 Scores on a Scale Standard Deviation 6.21
Change From Baseline in the Short Form Health Survey (SF-36) Physical Functioning (PF) Score Week 60	1.79 Scores on a Scale Standard Deviation 7.13	-0.19 Scores on a Scale Standard Deviation 5.63

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

The SF-36 is a 36-item, patient-reported survey of patient health. Higher scores indicate better outcomes while lower scores indicate more disability. The Physical Component Score is comprised of the Physical Functioning Scale, the Role-Physical Scale, the Bodily Pain Scale, and the General Health Scale. It is scaled from 0 to 100 with a score of 0 equivalent to maximum disability and a score of 100 equivalent to no disability.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Change From Baseline in the Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score Week 24	0.90 Scores on a Scale Standard Deviation 7.96	-0.75 Scores on a Scale Standard Deviation 4.82
Change From Baseline in the Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score Week 48	0.25 Scores on a Scale Standard Deviation 6.83	-1.92 Scores on a Scale Standard Deviation 6.69
Change From Baseline in the Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score Week 60	1.51 Scores on a Scale Standard Deviation 6.76	-1.51 Scores on a Scale Standard Deviation 6.66

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 24, Week 48, and Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups to which they were randomized.

The Lupus QoL assessment is a 34 item questionnaire across 8 domains that is designed to find out how systemic lupus erythematosus (SLE) affects a participant's life over the preceding 4 weeks. Scores range from 0 (worst QoL) to 100 (best QoL). Domains include physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue.

Outcome measures

Measure	MMF Withdrawal n=51 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=49 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Physical Health at Week 24	1.04 Scores on a Scale Standard Deviation 17.66	-1.11 Scores on a Scale Standard Deviation 9.20
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Physical Health at Week 48	0.46 Scores on a Scale Standard Deviation 14.06	-2.83 Scores on a Scale Standard Deviation 11.57
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Physical Health at Week 60	1.56 Scores on a Scale Standard Deviation 13.18	0.00 Scores on a Scale Standard Deviation 9.02
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Pain at Week 24	1.77 Scores on a Scale Standard Deviation 18.87	-0.17 Scores on a Scale Standard Deviation 10.67
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Pain at Week 48	1.60 Scores on a Scale Standard Deviation 16.72	-3.10 Scores on a Scale Standard Deviation 12.73
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Pain at Week 60	1.42 Scores on a Scale Standard Deviation 14.36	-0.19 Scores on a Scale Standard Deviation 12.39
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Planning at Week 24	3.90 Scores on a Scale Standard Deviation 17.28	0.35 Scores on a Scale Standard Deviation 16.75
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Planning at Week 48	-0.18 Scores on a Scale Standard Deviation 18.59	-5.43 Scores on a Scale Standard Deviation 16.66
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Planning at Week 60	0.18 Scores on a Scale Standard Deviation 17.76	-3.03 Scores on a Scale Standard Deviation 16.48
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Intimate Relationships at Week 24	4.29 Scores on a Scale Standard Deviation 18.68	-1.47 Scores on a Scale Standard Deviation 23.39
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Intimate Relationships at Week 48	-1.10 Scores on a Scale Standard Deviation 14.88	-0.81 Scores on a Scale Standard Deviation 10.67
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Intimate Relationships at Week 60	2.86 Scores on a Scale Standard Deviation 13.92	-2.08 Scores on a Scale Standard Deviation 10.93
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Burden to Others at Week 24	0.18 Scores on a Scale Standard Deviation 20.30	1.56 Scores on a Scale Standard Deviation 21.99
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Burden to Others at Week 48	-4.43 Scores on a Scale Standard Deviation 16.56	-0.58 Scores on a Scale Standard Deviation 16.20
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Burden to Others at Week 60	-3.55 Scores on a Scale Standard Deviation 18.78	-1.33 Scores on a Scale Standard Deviation 17.14
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Emotional Health at Week 24	0.09 Scores on a Scale Standard Deviation 13.02	-0.87 Scores on a Scale Standard Deviation 18.57
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Emotional Health at Week 48	-1.22 Scores on a Scale Standard Deviation 15.13	-2.03 Scores on a Scale Standard Deviation 15.71
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Emotional Health at Week 60	-0.87 Scores on a Scale Standard Deviation 13.06	-1.52 Scores on a Scale Standard Deviation 17.10
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Body Image at Week 24	-1.09 Scores on a Scale Standard Deviation 15.61	2.94 Scores on a Scale Standard Deviation 16.12
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Body Image at Week 48	-0.56 Scores on a Scale Standard Deviation 17.76	-0.17 Scores on a Scale Standard Deviation 14.84
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Body Image at Week 60	-4.45 Scores on a Scale Standard Deviation 20.15	3.22 Scores on a Scale Standard Deviation 15.29
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Fatigue at Week 24	-1.17 Scores on a Scale Standard Deviation 20.74	3.78 Scores on a Scale Standard Deviation 16.04
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Fatigue at Week 48	-1.56 Scores on a Scale Standard Deviation 17.37	-2.18 Scores on a Scale Standard Deviation 18.04
Change From Baseline in the Lupus Quality of Life (QoL)Score Change in Fatigue at Week 60	-1.95 Scores on a Scale Standard Deviation 17.69	-0.57 Scores on a Scale Standard Deviation 15.36

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups they were randomized. Participants who met primary endpoint were analyzed.

For each participant who experienced disease reactivation, time from clinically significant disease reactivation to improvement in BILAG from maximum level (at least an A or B) during the flare was calculated in study days as: date of clinically significant disease reactivation minus (-) date of BILAG improvement. If multiple body systems had a BILAG flare at the visit, then the body system with the most severe score was tracked for improvement; if multiple body systems had the same score (at least an A or B), then just one needed to show improvement.

Outcome measures

Measure	MMF Withdrawal n=9 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=5 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Time From Clinically Significant Disease Reactivation to Improvement in British Isles Lupus Assessment Group (BILAG) From Maximum Level During Flare	40.5 Days Standard Deviation 31.8	114.5 Days Standard Deviation 123.7

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups they were randomized. Participants who met primary endpoint were analyzed.

For each participant who experienced disease reactivation, time from clinically significant disease reactivation to recovery to baseline BILAG scores or BILAG C, whichever is worse, was calculated in study days as: date of clinically significant disease reactivation minus (-) date of BILAG recovery.

Outcome measures

Measure	MMF Withdrawal n=9 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=5 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Time From Clinically Significant Disease Reactivation to Recovery to Baseline British Isles Lupus Assessment Group (BILAG) Score or BILAG C	77.7 Days Standard Deviation 63.4	114.5 Days Standard Deviation 123.7

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups they were randomized. Participants who met primary endpoint were analyzed.

For each participant who experienced disease reactivation, excess systemic steroid dose was summed from the time of clinically significant disease reactivation until the dose returns to pre-flare levels or the end of study participation, whichever occurred first. Excess systemic steroid dose was defined as the total dose given for the flare minus (-) a participant's pre-flare steroid dose. Participants who do not have an increase in their steroid use due to the flare had their excess dose set to zero. Steroids include medications that code to a medication class which includes the terms "glucocorticoid" or "corticosteroid". Systemic steroids will include any of these steroids that are taken by mouth (PO), intravenous (IV), or intramuscular (IM).

Outcome measures

Measure	MMF Withdrawal n=9 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=5 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Cumulative Excess Systemic Steroid Dose From Time of Clinically Significant Disease Reactivation to Return to Pre-Flare Dose or End of Trial Participation	1750.7 Steroid dose (mg) Standard Deviation 3384.6	812.8 Steroid dose (mg) Standard Deviation 561.6

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The modified Intent-to-Treat (mITT) population included all randomized participants who begin ALE06-provided MMF and meet study entry criteria. Participants who, for whatever reason, do not complete their assigned therapy will be included in the mITT population in the groups they were randomized. Participants who met primary endpoint were analyzed.

For each participant who experienced disease reactivation, time from clinically significant disease reactivation to recovery to pre-flare steroid dose was calculated in study days as: date of clinically significant disease reactivation minus (-) date of return to pre-flare steroid dose.

Outcome measures

Measure	MMF Withdrawal n=9 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=5 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Time From Clinically Significant Disease Reactivation to Return to Pre-Flare Steroid Dose	37 Days Standard Deviation NA Six of the 14 subjects who met disease reactivation were on baseline steroids. Only 1 recovered to their baseline steroid dose.	NA Days Standard Deviation NA Six of the 14 subjects who met disease reactivation were on baseline steroids. Only 1 recovered to their baseline steroid dose.

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

The number of Grade 3, 4, or 5 AEs classified as possibly, probably, or definitely related to SLE. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Systemic Lupus Erythematosus (SLE) Grade 3	5 Adverse Events	6 Adverse Events
Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Systemic Lupus Erythematosus (SLE) Grade 4	0 Adverse Events	0 Adverse Events
Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Systemic Lupus Erythematosus (SLE) Grade 5	0 Adverse Events	0 Adverse Events

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

The number of Grade 3, 4, or 5 AEs classified as possibly, probably, or definitely related to MMF. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Mycophenolate Mofetil (MMF) Grade 3	1 Adverse Events	7 Adverse Events
Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Mycophenolate Mofetil (MMF) Grade 4	0 Adverse Events	0 Adverse Events
Number of Grade 3, 4, or 5 Adverse Events (AEs) Related to Mycophenolate Mofetil (MMF) Grade 5	0 Adverse Events	0 Adverse Events

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

The number of Grade 3, 4, or 5 AEs. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Grade 3, 4, or 5 Adverse Events (AEs) Grade 3	15 Adverse Events	18 Adverse Events
Number of Grade 3, 4, or 5 Adverse Events (AEs) Grade 4	0 Adverse Events	2 Adverse Events
Number of Grade 3, 4, or 5 Adverse Events (AEs) Grade 5	0 Adverse Events	0 Adverse Events

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

The number of SAEs. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Serious Adverse Events (SAEs).	6 Serious Adverse Events	12 Serious Adverse Events

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

The number of AEs classified as infections. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Infection-Related Adverse Events (AEs)	49 Adverse Events	63 Adverse Events

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

The number of malignancies reported as AEs. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Malignancies Reported as Adverse Events (AEs).	3 Adverse Events	2 Adverse Events

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

The number of Grade 3, 4, or 5 hematological AEs. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Number of Grade 3, 4, or 5 Hematological Adverse Events (AEs). Grade 3	0 Adverse Events	3 Adverse Events
Number of Grade 3, 4, or 5 Hematological Adverse Events (AEs). Grade 4	0 Adverse Events	0 Adverse Events
Number of Grade 3, 4, or 5 Hematological Adverse Events (AEs). Grade 5	0 Adverse Events	0 Adverse Events

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

Mortality related to SLE is defined as any death possibly, probably, or definitely related to SLE. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
Mortality Related to Systemic Lupus Erythematosus (SLE)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Treatment Randomization) to Week 60

Population: The safety population (SP) includes all participants for whom study intervention was initiated.

All-cause mortality is defined as death from any cause occurring after randomization. The severity of AEs was classified using the National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCI-CTCAE), Version 4.0.

Outcome measures

Measure	MMF Withdrawal n=52 Participants Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).	MMF Maintenance n=50 Participants Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).
All-Cause Mortality	0 Participants	0 Participants

Adverse Events

Maintenance

Serious events: 7 serious events

Other events: 38 other events

Deaths: 0 deaths

Withdrawal

Serious events: 5 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	Maintenance n=50 participants at risk Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).	Withdrawal n=52 participants at risk Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).
Blood and lymphatic system disorders Febrile neutropenia	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Cardiac disorders Acute coronary syndrome	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Cardiac disorders Myocardial ischaemia	4.0% 2/50 • Number of events 2 • 60 weeks	0.00% 0/52 • 60 weeks
Cardiac disorders Pericarditis	0.00% 0/50 • 60 weeks	1.9% 1/52 • Number of events 1 • 60 weeks
Gastrointestinal disorders Haematemesis	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Gastrointestinal disorders Pancreatitis	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Infections and infestations Bronchitis	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Infections and infestations Mastoiditis	0.00% 0/50 • 60 weeks	1.9% 1/52 • Number of events 1 • 60 weeks
Infections and infestations Pyelonephritis	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/50 • 60 weeks	1.9% 1/52 • Number of events 1 • 60 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Psychiatric disorders Psychotic disorder	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks
Renal and urinary disorders Lupus nephritis	0.00% 0/50 • 60 weeks	5.8% 3/52 • Number of events 3 • 60 weeks
Skin and subcutaneous tissue disorders Hidradenitis	2.0% 1/50 • Number of events 1 • 60 weeks	0.00% 0/52 • 60 weeks

Other adverse events

Measure	Maintenance n=50 participants at risk Participants received Mycophenolate Mofetil (MMF) treatment (1000-3000 mg/day) for the rest of their study participation (up to Week 60).	Withdrawal n=52 participants at risk Participants tapered off Mycophenolate Mofetil (MMF) per the protocol-specified schedule over 12 weeks and remained off MMF for the rest of their study participation (up to Week 60 or until the primary endpoint of disease reactivation was met, whichever came first).
Blood and lymphatic system disorders Anaemia	4.0% 2/50 • Number of events 2 • 60 weeks	9.6% 5/52 • Number of events 6 • 60 weeks
Blood and lymphatic system disorders Leukopenia	22.0% 11/50 • Number of events 17 • 60 weeks	25.0% 13/52 • Number of events 17 • 60 weeks
Blood and lymphatic system disorders Lymphopenia	16.0% 8/50 • Number of events 10 • 60 weeks	15.4% 8/52 • Number of events 9 • 60 weeks
Blood and lymphatic system disorders Neutropenia	10.0% 5/50 • Number of events 9 • 60 weeks	13.5% 7/52 • Number of events 9 • 60 weeks
Infections and infestations Bronchitis	2.0% 1/50 • Number of events 1 • 60 weeks	5.8% 3/52 • Number of events 3 • 60 weeks
Infections and infestations Sinusitis	4.0% 2/50 • Number of events 3 • 60 weeks	5.8% 3/52 • Number of events 3 • 60 weeks
Infections and infestations Tooth infection	2.0% 1/50 • Number of events 1 • 60 weeks	5.8% 3/52 • Number of events 3 • 60 weeks
Infections and infestations Upper respiratory tract infection	28.0% 14/50 • Number of events 20 • 60 weeks	13.5% 7/52 • Number of events 11 • 60 weeks
Infections and infestations Urinary tract infection	12.0% 6/50 • Number of events 9 • 60 weeks	19.2% 10/52 • Number of events 11 • 60 weeks
Investigations Blood creatinine increased	6.0% 3/50 • Number of events 4 • 60 weeks	5.8% 3/52 • Number of events 5 • 60 weeks
Investigations Glomerular filtration rate decreased	12.0% 6/50 • Number of events 8 • 60 weeks	3.8% 2/52 • Number of events 4 • 60 weeks
Metabolism and nutrition disorders Hypophosphataemia	10.0% 5/50 • Number of events 6 • 60 weeks	5.8% 3/52 • Number of events 3 • 60 weeks
Musculoskeletal and connective tissue disorders Arthralgia	8.0% 4/50 • Number of events 7 • 60 weeks	3.8% 2/52 • Number of events 2 • 60 weeks
Musculoskeletal and connective tissue disorders Arthritis	2.0% 1/50 • Number of events 1 • 60 weeks	7.7% 4/52 • Number of events 4 • 60 weeks
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/50 • 60 weeks	7.7% 4/52 • Number of events 5 • 60 weeks
Nervous system disorders Headache	4.0% 2/50 • Number of events 3 • 60 weeks	9.6% 5/52 • Number of events 7 • 60 weeks
Renal and urinary disorders Acute prerenal failure	2.0% 1/50 • Number of events 1 • 60 weeks	5.8% 3/52 • Number of events 6 • 60 weeks

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place