Trial Outcomes & Findings for Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis (NCT NCT00594932)

NCT ID: NCT00594932

Last Updated: 2020-10-09

Results Overview

Complete response at three months (This is defined as \</= 0.25 of the total tender plus swollen joints observed at baseline and British Isles Lupus Assessment Group (BILAG) index C (mild) or D (no longer present) score in the Musculoskeletal system), comparing treatment to placebo group as complete responder or not complete responder. This was an intent to treat analysis so dropouts were counted as non-responders.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 27 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2020-10-09

Participant Flow

A total of 27 patients with SLE and active arthritis (with or without other manifestations) were randomized 1:1 to receive mycophenolate mofetil (MMF) or placebo. A total of 13 received MMF and 14 received placebo for the first 3 months. For the second three months patients could elect to continue on open lable MMF

Patients were excluded if they did not have arthritis sufficient to be treated with an aggressive immune suppressant. All patients were offered steroid rescue at baseline, those who required immediate treatment and/or who could not be given steroids were excluded from the study

Participant milestones

Measure	Patients Who Received MMF for the First 3 Months 13 patients were randomized to receive MMF for the first 3 months. MMF was (blindly) increased to maximal tolerated dose or 3 gms/daily whichever was lowest.	Patients Who Received Placebo for the First 3 Months 14 patients were randomized to placebo for the first three months
First 3 Months STARTED	13	14
First 3 Months COMPLETED	12	11
First 3 Months NOT COMPLETED	1	3
Final 3 Months STARTED	12	11
Final 3 Months COMPLETED	8	8
Final 3 Months NOT COMPLETED	4	3

Reasons for withdrawal

Measure	Patients Who Received MMF for the First 3 Months 13 patients were randomized to receive MMF for the first 3 months. MMF was (blindly) increased to maximal tolerated dose or 3 gms/daily whichever was lowest.	Patients Who Received Placebo for the First 3 Months 14 patients were randomized to placebo for the first three months
First 3 Months Withdrawal by Subject	1	3
Final 3 Months Withdrawal by Subject	4	3

Baseline Characteristics

Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis

Baseline characteristics by cohort

Measure	Patients Who Received MMF for the First 3 Months n=13 Participants 13 patients were randomized to receive MMF for the first 3 months. MMF was (blindly) increased to maximal tolerated dose or 3 gms/daily whichever was lowest.	Patients Who Received Placebo for the First 3 Months n=14 Participants 14 patients were randomized to placebo for the first three months	Total n=27 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	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	38.9 years STANDARD_DEVIATION 9.42 • n=5 Participants	34.0 years STANDARD_DEVIATION 11.35 • n=7 Participants	36.3 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Complete response at three months (This is defined as </= 0.25 of the total tender plus swollen joints observed at baseline and British Isles Lupus Assessment Group (BILAG) index C (mild) or D (no longer present) score in the Musculoskeletal system), comparing treatment to placebo group as complete responder or not complete responder. This was an intent to treat analysis so dropouts were counted as non-responders.

Outcome measures

Measure	Patients Who Received MMF for the First 3 Months n=13 Participants 13 patients were randomized to receive MMF for the first 3 months. MMF was (blindly) increased to maximal tolerated dose or 3 gms/daily whichever was lowest.	Patients Who Received Placebo for the First 3 Months n=14 Participants 14 patients were randomized to placebo for the first three months
Arthritis Complete Response	4 participants	0 participants

SECONDARY outcome

Timeframe: 3 months

Population: All those randomized to MMF or placebo

This is defined as at least a 50% reduction in tender + swollen joint counts and severity rated as mild as defined by the British Isles Lupus Assessment Group Index

Outcome measures

Measure	Patients Who Received MMF for the First 3 Months n=13 Participants 13 patients were randomized to receive MMF for the first 3 months. MMF was (blindly) increased to maximal tolerated dose or 3 gms/daily whichever was lowest.	Patients Who Received Placebo for the First 3 Months n=14 Participants 14 patients were randomized to placebo for the first three months
Major Arthritis Response	5 participants	0 participants

SECONDARY outcome

Timeframe: 3 Months

Population: Patients who entered and were randomized to receive MMF vs Placebo.

Those meeting the Criteria for Major or Complete Clinical Response as listed in the preceding endpoints or who meet criteria for partial response defined as at least a 25% decrease in tender and swollen joint count and improvement of at least one severity rating for arthritis as at least one level on the British Isles Lupus Assessment Group Index.

Outcome measures

Measure	Patients Who Received MMF for the First 3 Months n=13 Participants 13 patients were randomized to receive MMF for the first 3 months. MMF was (blindly) increased to maximal tolerated dose or 3 gms/daily whichever was lowest.	Patients Who Received Placebo for the First 3 Months n=14 Participants 14 patients were randomized to placebo for the first three months
Major and Partial Clinical Response	9 participants	5 participants

Adverse Events

Mycophenolate Mofetil

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Mycophenolate Mofetil n=13 participants at risk；n=24 participants at risk Patients receiving mycophenolate mofetil from baseline throughout their participation in the study (up to six months). Mycophenolate is a standard of care treatment for SLE, and the primary endpoint was at three months, after which mycophenolate was given "open lable." This trial did not collect adverse events after three months in any formal manner that can be reported here. However there were no deaths so we can report that for six months. We can also report serious adverse events for all six months. Therefore deaths and serious adverse events are reported for six months and placebo crossovers are included in the "at risk" population for a total of 24 at risk. However non serious adverse events can only be reported for three months so the population at risk remains at 13 for non serious adverse events.	Placebo n=14 participants at risk Patients receiving placebo for the first three months. They were then offered mycophenolate mofetil for up to three more months. Since this is a standard of care for SLE formal assessment of adverse events was not performed during the second three months. We cannot provide any data after the first three months on placebo patients since there were no placebo patients after the first three months. Therefore the at risk population on placebo is 14 and the reporting period is 3 months for them. This is true for all types of adverse events since there was no placebo group after 3 months.
Musculoskeletal and connective tissue disorders Chest pain	4.2% 1/24 • Number of events 1 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.	0.00% 0/14 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.
Gastrointestinal disorders upper GI bleed	4.2% 1/24 • Number of events 1 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.	0.00% 0/14 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.
Blood and lymphatic system disorders groin abcess	0.00% 0/24 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.	7.1% 1/14 • Number of events 1 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.
Musculoskeletal and connective tissue disorders avascular necrosis	0.00% 0/24 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.	7.1% 1/14 • Number of events 1 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.

Other adverse events

Measure	Mycophenolate Mofetil n=13 participants at risk；n=24 participants at risk Patients receiving mycophenolate mofetil from baseline throughout their participation in the study (up to six months). Mycophenolate is a standard of care treatment for SLE, and the primary endpoint was at three months, after which mycophenolate was given "open lable." This trial did not collect adverse events after three months in any formal manner that can be reported here. However there were no deaths so we can report that for six months. We can also report serious adverse events for all six months. Therefore deaths and serious adverse events are reported for six months and placebo crossovers are included in the "at risk" population for a total of 24 at risk. However non serious adverse events can only be reported for three months so the population at risk remains at 13 for non serious adverse events.	Placebo n=14 participants at risk Patients receiving placebo for the first three months. They were then offered mycophenolate mofetil for up to three more months. Since this is a standard of care for SLE formal assessment of adverse events was not performed during the second three months. We cannot provide any data after the first three months on placebo patients since there were no placebo patients after the first three months. Therefore the at risk population on placebo is 14 and the reporting period is 3 months for them. This is true for all types of adverse events since there was no placebo group after 3 months.
Infections and infestations mild to moderate infection (includes respiratory tract, urinary tract, vaginitis, non serious abcess	69.2% 9/13 • Number of events 16 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.	57.1% 8/14 • Number of events 13 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.
Gastrointestinal disorders gastroenteritis	61.5% 8/13 • Number of events 15 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.	35.7% 5/14 • Number of events 9 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.
General disorders Other mild or moderate AEs	53.8% 7/13 • Number of events 7 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.	85.7% 12/14 • Number of events 13 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.
Metabolism and nutrition disorders Renal Stones	7.7% 1/13 • Number of events 1 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.	7.1% 1/14 • Number of events 1 • 3 months for non serious adverse events and six months for deaths and serious adverse events. We did not formally collect adverse events after the end of the double blind part of the study since all continuing patients received open lable MMF, a standard of care for SLE. Since we are confident that there were no additional deaths or serious adverse events over six months, we can report those for the entire six month period but we only have non serious adverse events collected for three months. Definitions do not differ. However we only collected accurate non-serious adverse events for the first three months. After that it was no longer a blinded trial, those who wanted to continue were receiving MMF, a standard of care for SLE. Safety of this commonly used drug would not be interpretable in a tiny trial after the double blind period. However, we can report SAEs for six months, since we are confident we can be accurate about those. There were also no deaths over six months.

Additional Information

Joan T Merrill M.D.

Oklahoma Medical Research Foundation

Phone: 405 271 7805

Email: joan-merrill@omrf.org

Results disclosure agreements

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