Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease

• Sponsor: Mallinckrodt (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01753401
• Collaborator: (none)
• Enrollment: 38
• Locations: 22
• Arms: 4
• Actual Duration (Months): 33
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This Phase 4 study is being performed to examine the effects of Acthar for the indicated use of treatment of SLE. This study will enroll patients with steroid-dependent, persistently active SLE with arthritic and/or cutaneous involvement.

The study will involve two periods: an 8-week double-blind period, to provide placebo-controlled safety, efficacy, and pharmacodynamic data, and an optional open-label period, to examine the prolonged effects of Acthar maintenance.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus (SLE)	Drug: Acthar; Drug: Placebo; Drug: Steroid Drug	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Two-part Study Exploring the Efficacy, Safety, and Pharmacodynamics of Acthar in Systemic Lupus Erythematosus Patients With a History of Persistently Active Disease
• Actual Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Period 2: Placebo/Acthar Participants receive Placebo in Part 1, but after completion of Week 8 in the double-blind phase, patients who received Placebo may choose to participate in the optional open-label phase where they will receive an Acthar maintenance regimen for 44 weeks. The initial Acthar regimen will be assigned based on the study medication regimen the patient received at the completion of the double-blind phase (Visit 6, Week 8). Acthar regimen during Part 2 may be adjusted based on the Investigator's judgment with the goal of achieving a stable Acthar regimen no later than Week 28. Once the stable Acthar regimen is achieved, the Investigator should consider tapering the steroid regimen to a low daily dose or completely discontinue.	Drug: Acthar; Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day; Other Names: H.P. Acthar Gel Repository Corticotropin Injection ; Drug: Placebo; Placebo contains the same inactive ingredients as Acthar, and is given by SC injection; Other Names: Matching Placebo ; Drug: Steroid Drug; The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.; Other Names: Prednisone or equivalent
Experimental: Period 2: Acthar/Acthar After completion of Week 8 in the double-blind phase, patients who received Acthar may choose to participate in the optional open-label phase where they will receive an Acthar maintenance regimen for 44 weeks. The initial Acthar regimen will be assigned based on the study medication regimen the patient received at the completion of the double-blind phase (Visit 6, Week 8). Acthar regimen may be adjusted based on the Investigator's judgment with the goal of achieving a stable Acthar regimen no later than Week 28. Once the stable Acthar regimen is achieved, the Investigator should consider tapering the steroid regimen to a low daily dose or completely discontinue.	Drug: Acthar; Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day; Other Names: H.P. Acthar Gel Repository Corticotropin Injection ; Drug: Steroid Drug; The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.; Other Names: Prednisone or equivalent
Placebo Comparator: Period 1: Placebo Participants receive matching placebo (in 0.5 mL daily or in 1 mL every other day) for 4 weeks. In Weeks 5-8, they will taper the study medication. Participants will continue on their stable steroid regimen during this phase of the study. After completion of Week 8 in the double-blind phase, they may choose to participate in the optional open-label phase. Participants will continue on their stable steroid regimen during this phase of the study.	Drug: Placebo; Placebo contains the same inactive ingredients as Acthar, and is given by SC injection; Other Names: Matching Placebo ; Drug: Steroid Drug; The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.; Other Names: Prednisone or equivalent
Experimental: Period 1: Acthar Participants receive Acthar (40 units in 0.5 mL daily or 80 units in 1 mL every other day) for 4 weeks. In Weeks 5-8, they will taper the study medication. Participants will continue on their stable steroid regimen during this phase of the study. After completion of Week 8 in the double-blind phase, they may choose to participate in the optional open-label phase. Participants will continue on their stable steroid regimen during this phase of the study.	Drug: Acthar; Acthar is given by subcutaneous (SC) injection (shot under the skin), at a dose of 40 units daily or 80 units every other day; Other Names: H.P. Acthar Gel Repository Corticotropin Injection ; Drug: Steroid Drug; The patient's steroid regimen 7.5 to 30 mg/day of prednisone or equivalent, chronic/stable within the 4 weeks prior to screening.; Other Names: Prednisone or equivalent

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Meet the Definition of a Responder Within 4 Weeks [within 4 weeks]

   Participants are counted as responders based on two SLE indices: the Systemic Lupus Erythematosus Disease Activity Index amended by the SELENA group (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) Index. decrease in SELENA-SLEDAI score from 4 to 0 for the arthritis descriptor (highest possible score is 4) and no worsening in other organ systems based on BILAG OR decrease in SELENA-SLEDAI score from 2 to 0 for rash (highest possible score is 2) and no worsening in other organ systems based on BILAG The BILAG is a transitional index that captures changing severity of clinical manifestations. It has an ordinal scale scoring system by design that produces an overview of disease activity across eight systems. The individual system scores were not intended to be summated into a global score.

Secondary Outcome Measures

1. Number of Participants Who Meet the Definition of a Responder Within 8 Weeks [within 8 weeks]

   Participants are counted as responders based on: decrease in SELENA-SLEDAI score from 4 to 0 for arthritis and no worsening in other organ systems based on BILAG OR decrease in SELENA-SLEDAI score from 2 to 0 for rash and no worsening in other organ systems based on BILAG

2. Score on the SELENA-SLEDAI Within 8 Weeks [within 8 weeks]

   SLEDAI was modeled on the basis of clinician global judgment. A participant's SELENA-SLEDAI total score is the sum of all marked SLE-related descriptors on a checklist developed by the SELENA Group (also referred to as hybrid SLEDAI). The scores of the descriptors range from 0 to 8. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity. Rows: Week 2, Week 4, Week 6, Week 8

3. BILAG Total Score Within 8 Weeks [within 8 weeks]

   The BILAG is a transitional index that captures changing severity of clinical manifestations that produces an overview of disease activity across eight systems. The 8 systems are scored on a scale from 0=not present to 4=worse, for the 4 week period before the assessment. The lowest possible score is 0, and the highest possible score is 32. A higher score means the symptoms are worse. Rows: Baseline, Week 4, Week 8

4. Physician's Global Assessment (PGA) of Disease Severity at Baseline [at Baseline]

   PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.

5. Physician's Global Assessment (PGA) of Disease Severity at Week 4 [at Week 4]

   PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.

6. Physician's Global Assessment (PGA) of Disease Severity at Week 8 [at Week 8]

   PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.

7. Number of Tender or Swollen Joints Within 8 Weeks [at Baseline, Week 4, and Week 8 (within 8 weeks)]

   The doctor counted the number of tender or swollen joints at Baseline, at Week 4, and at Week 8

8. Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Within 8 Weeks [at Baseline, Week 4 and Week 8 (within 8 weeks)]

   The CLASI consists of two scores the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI score ranges from 0 to 70, with higher scores indicating more severe skin disease. Rows: at Baseline, at Week 4, at Week 8

9. Krupp Fatigue Severity Score (FSS) Within 8 Weeks [at Baseline, Week 4 and Week 8 (within 8 weeks)]

   The Krupp FSS is a scale to rate disability-related fatigue. Respondents use a scale ranging from 1 ("completely disagree") to 7 ("completely agree") to indicate their agreement with nine statements about fatigue. A visual analogue scale is also included with the scale; respondents are asked to denote the severity of their fatigue over the past 2 weeks by placing a mark on a line extending from "no fatigue" to "fatigue as bad as could be." Higher scores on the scale are indicative of more severe fatigue. This validated fatigue severity scale measures impact of fatigue with a 9-item questionnaire, with a 7-point Likert scale for each question. Total score ranges from 0 (best possible outcome) to 63 (worst possible fatigue). Rows: at Baseline, at Week 4, at Week 8

10. Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks [at Baseline, Week 4 and Week 8 (within 8 weeks)]

    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement. Rows: at Baseline, at Week 4, at Week 8

11. Mean Score on the Mental Component Scale (MCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks [at Baseline, Week 4 and Week 8 (within 8 weeks)]

    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.

12. Number of Participants Who Meet the Definition of a Responder at Week 52 [at Week 52]

    Participants are counted as responders based on: decrease in SELENA-SLEDAI score from 4 to 0 for arthritis and no worsening in other organ systems based on BILAG OR decrease in SELENA-SLEDAI score from 2 to 0 for rash and no worsening in other organ systems based on BILAG

13. Score on the SELENA-SLEDAI at Week 52 [at Week 52]

    SLEDAI was modeled on the basis of clinician global judgment. A participant's SELENA-SLEDAI total score is the sum of all marked SLE-related descriptors on a checklist developed by the SELENA Group (also referred to as hybrid SLEDAI). The scores of the descriptors range from 0 to 8. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.

14. Physician's Global Assessment (PGA) of Disease Severity at Week 52 [at Week 52]

    PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.

15. Number of Tender or Swollen Joints at Week 52 [at Week 52]

    The doctor counted the number of tender or swollen joints at Week 52.

16. Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) at Week 52 [at Week 52]

    The CLASI consists of two scores the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI score ranges from 0 to 70, with higher scores indicating more severe skin disease.

17. Krupp Fatigue Severity Score (FSS) at Week 52 [at Week 52]

    The Krupp FSS is a scale to rate disability-related fatigue. Respondents use a scale ranging from 1 ("completely disagree") to 7 ("completely agree") to indicate their agreement with nine statements about fatigue. A visual analogue scale is also included with the scale; respondents are asked to denote the severity of their fatigue over the past 2 weeks by placing a mark on a line extending from "no fatigue" to "fatigue as bad as could be." Higher scores on the scale are indicative of more severe fatigue. This validated fatigue severity scale measures impact of fatigue with a 9-item questionnaire, with a 7-point Likert scale for each question. Total score ranges from 0 (best possible outcome) to 63 (worst possible fatigue).

18. Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52 [at Week 52]

    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.

19. Mean Score on the Mental Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52 [at Week 52]

    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.

20. Number of Participants With a Relapse Within 52 Weeks [within 52 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female ≥ 18 years of age at screening who are able to provide informed consent

• Diagnosis of SLE according to the American College of Rheumatology revised criteria (fulfilled ≥ 4 criteria)

• Active SLE with arthritic and/or cutaneous involvement as demonstrated by a SELENA-SLEDAI score ≥ 2 (clinical manifestation must include rash and/or arthritis)

• Moderate to severe rash and/or arthritis as demonstrated by BILAG score A or B in the mucocutaneous and/or musculoskeletal body systems

• Documented history of autoantibodies to at least one of the following: anti-dsDNA, anti-Smith, or anti-cardiolipin

• Documented history of positive antinuclear antibody (ANA)

• Currently on a stable dose of prednisone (7.5 to 30 mg/day of prednisone or equivalent within the 4 weeks prior to screening). The prednisone regimen must remain stable through the double-blind phase and until the stable Acthar regimen is attained in the open-label phase.

Exclusion Criteria:

• Patients with a recent history (≤ 2 months prior to screening) of starting prednisone (or equivalent) use

• Patients with active nephritis defined as serum creatinine > 2.5 mg/dL or protein creatinine ratio (PCR) > 1.5 g/g, or patients that required hemodialysis within 3 months prior to screening

• Active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis, or CNS vasculitis), requiring therapeutic intervention within 3 months prior to screening

• Type 1 or type 2 diabetes mellitus (history of gestational diabetes mellitus is not an exclusion), or patients currently taking hypoglycemic medication

• History of using certain medications prior to screening:

1. oral prednisone (or equivalent) > 30 mg/day, any steroid injection, cyclosporine, or non-biologic investigational drug within 3 months prior to screening

2. intravenous immunoglobulin (IVIg) or plasmapheresis within 4 months prior to screening

3. cyclophosphamide within 6 months prior to screening; and/or

4. B-cell targeted therapy, abatacept, or any biologic investigational agent within 12 months prior to screening

• Contraindication per Acthar Prescribing Information: scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, or adrenal cortical hyperfunction

1. For the purposes of this study, osteoporosis is defined as evidence of vertebral or long bone fracture or vertebral T-score > 2.0

2. For the purposes of this study, history of peptic ulcer is defined as ≤ 6 months prior to screening

3. For the purposes of this study, congestive heart failure is defined as New York Heart Association Functional Class III-IV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mallinckrodt Investigational Site	Jonesboro	Arkansas	United States	72401
2	Mallinckrodt Investigational Site	La Jolla	California	United States	92037
3	Mallinckrodt Investigational Site	La Palma	California	United States	90623
4	Mallinckrodt Investigational Site	Long Beach	California	United States	90806
5	Mallinckrodt Investigational Site	Upland	California	United States	91786
6	Mallinckrodt Investigational Site	Brandon	Florida	United States	33511
7	Mallinckrodt Investigational Site	Clearwater	Florida	United States	33765
8	Mallinckrodt Investigational Site	Miami Lakes	Florida	United States	33014
9	Mallinckrodt Investigational Site	Orlando	Florida	United States	32806
10	Mallinckrodt Investigational Site	Tampa	Florida	United States	33614
11	Mallinckrodt Investigational Site	Granger	Indiana	United States	46530
12	Mallinckrodt Investigational Site	Baton Rouge	Louisiana	United States	70809
13	Mallinckrodt Investigational Site	Lansing	Michigan	United States	48910
14	Mallinckrodt Investigational Site	Lansing	Michigan	United States	48917
15	Mallinckrodt Investigational Site	Brooklyn	New York	United States	11201
16	Mallinckrodt Investigational Site	Great Neck	New York	United States	11020
17	Mallinckrodt Investigational Site	New York	New York	United States	10016
18	Mallinckrodt Investigational Site	Charlotte	North Carolina	United States	28210
19	Mallinckrodt Investigational Site	Hershey	Pennsylvania	United States	17033
20	Mallinckrodt Investigational Site	Wyomissing	Pennsylvania	United States	19610
21	Mallinckrodt Investigational Site	Houston	Texas	United States	77004
22	Mallinckrodt Investigational Site	Houston	Texas	United States	77034

Sponsors and Collaborators

• Mallinckrodt

Investigators

• Study Director: Global Clinical Leader, Mallinckrodt

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT01753401
• Other Study ID Numbers: QSC01-SLE-01
• First Posted: Dec 20, 2012
• Last Update Posted: Feb 27, 2020
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mallinckrodt: SLE; Lupus
• Additional relevant MeSH terms: Lupus Erythematosus, Systemic; Prednisone; Adrenocorticotropic Hormone

Study Results

Participant Flow

Recruitment Details	38 enrolled participants were randomized 2:1:2:1 into four treatment groups, to receive Acthar 0.5 mL daily: Placebo 0.5 mL daily: Acthar 1 mL every other day: Placebo 1 mL every other day, during the double-blind period, along with their stable dose of steroids.
Pre-assignment Detail	All participants were to receive their stable steroid regimen in addition to the study drug throughout the double-blind period (Period 1). If they completed Period 1, they were invited to participate in an open label period (Period 2). Those who received Placebo went into Placebo/Acthar, and those who received Acthar went into Acthar/Acthar.

Arm/Group Title	Placebo	Acthar	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants receive their randomized regimen of placebo during the double-blind period	Participants receive their randomized regimen of Acthar during the double-blind period	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Period Title: Double-blind Period (8 Weeks)
STARTED	12	26	0	0
Modified Intent to Treat (mITT)	11	25	0	0
COMPLETED	11	22	0	0
NOT COMPLETED	1	4	0	0
Period Title: Double-blind Period (8 Weeks)
STARTED	0	0	11	22
mITT	0	0	11	22
Safety Analysis Set	0	0	11	22
COMPLETED	0	0	7	13
NOT COMPLETED	0	0	4	9

Baseline Characteristics

Arm/Group Title	Placebo	Acthar	Total
Arm/Group Description	Participants who were randomized to receive Placebo in Period 1	Participants who were randomized to receive Acthar in Period 1	Total of all reporting groups
Overall Participants	11	25	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	39	43	41.5
Sex: Female, Male (Count of Participants)
Female	10 90.9%	24 96%	34 94.4%
Male	1 9.1%	1 4%	2 5.6%
Race/Ethnicity, Customized (Count of Participants)
White or Caucasian	5 45.5%	6 24%	11 30.6%
Black or African American	6 54.5%	18 72%	24 66.7%
Other	0 0%	1 4%	1 2.8%
Hispanic or Latino Ethnicity	0 0%	6 24%	6 16.7%
Region of Enrollment (participants) [Number]
United States	11 100%	25 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Meet the Definition of a Responder Within 4 Weeks
Description	Participants are counted as responders based on two SLE indices: the Systemic Lupus Erythematosus Disease Activity Index amended by the SELENA group (SELENA-SLEDAI) and the British Isles Lupus Assessment Group (BILAG) Index. decrease in SELENA-SLEDAI score from 4 to 0 for the arthritis descriptor (highest possible score is 4) and no worsening in other organ systems based on BILAG OR decrease in SELENA-SLEDAI score from 2 to 0 for rash (highest possible score is 2) and no worsening in other organ systems based on BILAG The BILAG is a transitional index that captures changing severity of clinical manifestations. It has an ordinal scale scoring system by design that produces an overview of disease activity across eight systems. The individual system scores were not intended to be summated into a global score.
Time Frame	within 4 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
Count of Participants [Participants]	3 27.3%	4 16%

2. Secondary Outcome

Title	Number of Participants Who Meet the Definition of a Responder Within 8 Weeks
Description	Participants are counted as responders based on: decrease in SELENA-SLEDAI score from 4 to 0 for arthritis and no worsening in other organ systems based on BILAG OR decrease in SELENA-SLEDAI score from 2 to 0 for rash and no worsening in other organ systems based on BILAG
Time Frame	within 8 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
Count of Participants [Participants]	3 27.3%	11 44%

3. Secondary Outcome

Title	Score on the SELENA-SLEDAI Within 8 Weeks
Description	SLEDAI was modeled on the basis of clinician global judgment. A participant's SELENA-SLEDAI total score is the sum of all marked SLE-related descriptors on a checklist developed by the SELENA Group (also referred to as hybrid SLEDAI). The scores of the descriptors range from 0 to 8. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity. Rows: Week 2, Week 4, Week 6, Week 8
Time Frame	within 8 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
Week 2	10.0	8.0
Week 4	9.0	8.0
Week 6	8.0	6.0
Week 8	9.0	6.0

4. Secondary Outcome

Title	BILAG Total Score Within 8 Weeks
Description	The BILAG is a transitional index that captures changing severity of clinical manifestations that produces an overview of disease activity across eight systems. The 8 systems are scored on a scale from 0=not present to 4=worse, for the 4 week period before the assessment. The lowest possible score is 0, and the highest possible score is 32. A higher score means the symptoms are worse. Rows: Baseline, Week 4, Week 8
Time Frame	within 8 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
at Baseline	15.4 (9.55)	15.7 (5.93)
at Week 4	10.3 (7.80)	9.2 (5.36)
at Week 8	13.5 (8.82)	6.8 (4.31)

5. Secondary Outcome

Title	Physician's Global Assessment (PGA) of Disease Severity at Baseline
Description	PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.
Time Frame	at Baseline

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
None	0 0%	0 0%
Mild	1 9.1%	2 8%
Moderate	8 72.7%	19 76%
Severe	2 18.2%	4 16%
Missing	0 0%	0 0%

6. Secondary Outcome

Title	Physician's Global Assessment (PGA) of Disease Severity at Week 4
Description	PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.
Time Frame	at Week 4

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
None	0 0%	1 4%
Mild	5 45.5%	9 36%
Moderate	3 27.3%	11 44%
Severe	2 18.2%	1 4%
Missing	1 9.1%	3 12%

7. Secondary Outcome

Title	Physician's Global Assessment (PGA) of Disease Severity at Week 8
Description	PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.
Time Frame	at Week 8

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
None	0 0%	2 8%
Mild	5 45.5%	12 48%
Moderate	3 27.3%	7 28%
Severe	3 27.3%	1 4%
Missing	0 0%	3 12%

8. Secondary Outcome

Title	Number of Tender or Swollen Joints Within 8 Weeks
Description	The doctor counted the number of tender or swollen joints at Baseline, at Week 4, and at Week 8
Time Frame	at Baseline, Week 4, and Week 8 (within 8 weeks)

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
at Baseline	6.2 (5.40)	9.6 (6.90)
at Week 4	3.8 (4.34)	4.5 (4.94)
at Week 8	4.0 (6.18)	3.5 (5.89)

9. Secondary Outcome

Title	Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Within 8 Weeks
Description	The CLASI consists of two scores the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI score ranges from 0 to 70, with higher scores indicating more severe skin disease. Rows: at Baseline, at Week 4, at Week 8
Time Frame	at Baseline, Week 4 and Week 8 (within 8 weeks)

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
at Baseline	6.1 (6.63)	6.4 (6.33)
at Week 4	6.3 (4.60)	4.8 (4.08)
at Week 8	5.7 (6.87)	3.7 (4.24)

10. Secondary Outcome

Title	Krupp Fatigue Severity Score (FSS) Within 8 Weeks
Description	The Krupp FSS is a scale to rate disability-related fatigue. Respondents use a scale ranging from 1 ("completely disagree") to 7 ("completely agree") to indicate their agreement with nine statements about fatigue. A visual analogue scale is also included with the scale; respondents are asked to denote the severity of their fatigue over the past 2 weeks by placing a mark on a line extending from "no fatigue" to "fatigue as bad as could be." Higher scores on the scale are indicative of more severe fatigue. This validated fatigue severity scale measures impact of fatigue with a 9-item questionnaire, with a 7-point Likert scale for each question. Total score ranges from 0 (best possible outcome) to 63 (worst possible fatigue). Rows: at Baseline, at Week 4, at Week 8
Time Frame	at Baseline, Week 4 and Week 8 (within 8 weeks)

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
at Baseline	5.374 (0.9840)	5.648 (1.3091)
at Week 4	5.379 (1.0697)	5.298 (1.5401)
at Week 8	5.404 (1.1699)	5.152 (1.7858)

11. Secondary Outcome

Title	Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement. Rows: at Baseline, at Week 4, at Week 8
Time Frame	at Baseline, Week 4 and Week 8 (within 8 weeks)

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
at Baseline	32.927 (12.3561)	31.526 (11.7065)
at Week 4	32.831 (13.5390)	35.318 (12.5159)
at Week 8	33.310 (12.9760)	35.701 (11.8032)

12. Secondary Outcome

Title	Mean Score on the Mental Component Scale (MCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.
Time Frame	at Baseline, Week 4 and Week 8 (within 8 weeks)

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Placebo	Acthar
Arm/Group Description	Participants who receive Placebo in Period 1	Participants who receive Acthar in Period 1
Measure Participants	11	25
at Baseline	41.304 (11.8440)	38.406 (14.6618)
at Week 4	38.744 (16.8434)	40.280 (13.0274)
at Week 8	39.256 (18.4576)	40.408 (15.8738)

13. Secondary Outcome

Title	Number of Participants Who Meet the Definition of a Responder at Week 52
Description	Participants are counted as responders based on: decrease in SELENA-SLEDAI score from 4 to 0 for arthritis and no worsening in other organ systems based on BILAG OR decrease in SELENA-SLEDAI score from 2 to 0 for rash and no worsening in other organ systems based on BILAG
Time Frame	at Week 52

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	7	13
Count of Participants [Participants]	4 36.4%	3 12%

14. Secondary Outcome

Title	Score on the SELENA-SLEDAI at Week 52
Description	SLEDAI was modeled on the basis of clinician global judgment. A participant's SELENA-SLEDAI total score is the sum of all marked SLE-related descriptors on a checklist developed by the SELENA Group (also referred to as hybrid SLEDAI). The scores of the descriptors range from 0 to 8. A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.
Time Frame	at Week 52

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	7	13
Median (Full Range) [score on a scale]	3	4

15. Secondary Outcome

Title	Physician's Global Assessment (PGA) of Disease Severity at Week 52
Description	PGA of disease severity on a 100 mm visual analogue scale are categorized to the following: 0 point (none) = 0 mm; 1 point (mild) = >0 - 33.33 mm; 2 points (moderate) = >33.33 - 66.67 mm; and 3 points (severe) = >66.67 - 100 mm. The count of participants in each category is reported.
Time Frame	at Week 52

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	11	22
None	0 0%	4 16%
Mild	7 63.6%	7 28%
Moderate	0 0%	2 8%
Severe	0 0%	0 0%
Missing	4 36.4%	9 36%

16. Secondary Outcome

Title	Number of Tender or Swollen Joints at Week 52
Description	The doctor counted the number of tender or swollen joints at Week 52.
Time Frame	at Week 52

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	7	13
Mean (Standard Deviation) [Tender or Swollen Joints]	1.1 (2.27)	0.7 (2.21)

17. Secondary Outcome

Title	Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) at Week 52
Description	The CLASI consists of two scores the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored on the basis of erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The CLASI score ranges from 0 to 70, with higher scores indicating more severe skin disease.
Time Frame	at Week 52

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	7	13
Mean (Standard Deviation) [score on a scale]	0.4 (0.79)	1.3 (1.55)

18. Secondary Outcome

Title	Krupp Fatigue Severity Score (FSS) at Week 52
Description	The Krupp FSS is a scale to rate disability-related fatigue. Respondents use a scale ranging from 1 ("completely disagree") to 7 ("completely agree") to indicate their agreement with nine statements about fatigue. A visual analogue scale is also included with the scale; respondents are asked to denote the severity of their fatigue over the past 2 weeks by placing a mark on a line extending from "no fatigue" to "fatigue as bad as could be." Higher scores on the scale are indicative of more severe fatigue. This validated fatigue severity scale measures impact of fatigue with a 9-item questionnaire, with a 7-point Likert scale for each question. Total score ranges from 0 (best possible outcome) to 63 (worst possible fatigue).
Time Frame	at Week 52

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	7	13
Mean (Standard Deviation) [score on a scale]	4.523 (1.5491)	4.743 (2.0428)

19. Secondary Outcome

Title	Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.
Time Frame	at Week 52

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	6	13
Mean (Standard Deviation) [score on a scale]	43.618 (11.9596)	39.710 (10.8066)

20. Secondary Outcome

Title	Mean Score on the Mental Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Higher scores indicate improvement.
Time Frame	at Week 52

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	6	13
Mean (Standard Deviation) [score on a scale]	45.272 (12.6597)	39.700 (16.3027)

21. Secondary Outcome

Title	Number of Participants With a Relapse Within 52 Weeks
Time Frame	within 52 weeks

Outcome Measure Data

Analysis Population Description

mITT with necessary data at Week 52

Arm/Group Title	Placebo/Acthar	Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Part 1, but Acthar in Part 2	Participants who receive Acthar in both Parts 1 and 2
Measure Participants	5	19
Count of Participants [Participants]	1 9.1%	6 24%

Adverse Events

Time Frame	Period 1: within 8 Weeks of double-blind period, Period 2: within 44 Weeks of open-label period
Adverse Event Reporting Description	All treatment-emergent adverse events are listed in the non-serious AE module. Participants are counted only once per term.
Arm/Group Title	Period 1: Placebo		Period 1: Acthar		Period 2: Placebo/Acthar		Period 2: Acthar/Acthar
Arm/Group Description	Participants who receive Placebo in Period 1		Participants who receive Acthar in Period 1		Participants who receive Placebo in Period 1, but Acthar in Period 2		Participants who receive Acthar in both Periods 1 and 2
All Cause Mortality
	Period 1: Placebo		Period 1: Acthar		Period 2: Placebo/Acthar		Period 2: Acthar/Acthar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Period 1: Placebo		Period 1: Acthar		Period 2: Placebo/Acthar		Period 2: Acthar/Acthar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		3/25 (12%)		4/11 (36.4%)		2/22 (9.1%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Abdominal pain lower	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
General disorders
Chest discomfort	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Multi-organ failure	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Non-cardiac chest pain	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Infections and infestations
Klebsiella sepsis	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Necrotising fasciitis	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Viral infection	0/11 (0%)		1/25 (4%)		1/11 (9.1%)		0/22 (0%)
Pelvic abscess	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Pelvic infection	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Pyelonephritis	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Investigations
Liver function test abnormal	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Reproductive system and breast disorders
Haemorrhagic ovarian cyst	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Period 1: Placebo		Period 1: Acthar		Period 2: Placebo/Acthar		Period 2: Acthar/Acthar
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)		19/25 (76%)		8/11 (72.7%)		19/22 (86.4%)
Blood and lymphatic system disorders
Anaemia	1/11 (9.1%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Leukopenia	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Iron deficiency anaemia	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Microcytic anaemia	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Cardiac disorders
Tachycardia	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		1/22 (4.5%)
Ear and labyrinth disorders
Ear haemorrhage	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Eye disorders
Conjunctivitis	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Diplopia	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Keratitis	1/11 (9.1%)		0/25 (0%)		0/11 (0%)		0/22 (0%)
Dry eye	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Retinal degeneration	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Ulcerative keratitis	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Vision blurred	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Visual impairment	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Gastrointestinal disorders
Abdominal pain	0/11 (0%)		2/25 (8%)		0/11 (0%)		1/22 (4.5%)
Diarrhoea	0/11 (0%)		2/25 (8%)		0/11 (0%)		1/22 (4.5%)
Dyspepsia	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Gastrooesophageal reflux disease	0/11 (0%)		1/25 (4%)		1/11 (9.1%)		1/22 (4.5%)
Glossodynia	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Nausea	1/11 (9.1%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Swollen tongue	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Vomiting	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Abdominal pain lower	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Rectal haemorrhage	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Rectal prolapse	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
General disorders
Asthenia	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Chest discomfort	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Fatigue	0/11 (0%)		2/25 (8%)		0/11 (0%)		1/22 (4.5%)
Injection site haematoma	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Irritability	0/11 (0%)		2/25 (8%)		0/11 (0%)		0/22 (0%)
Multi-organ failure	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Non-cardiac chest pain	0/11 (0%)		1/25 (4%)		1/11 (9.1%)		1/22 (4.5%)
Oedema peripheral	0/11 (0%)		1/25 (4%)		1/11 (9.1%)		3/22 (13.6%)
Thirst	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Injection site pain	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Nodule	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Infections and infestations
Ear infection	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Gastroenteritis	0/11 (0%)		1/25 (4%)		0/11 (0%)		1/22 (4.5%)
Influenza	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Klebsiella sepsis	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Necrotising fasciitis	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Sinusitis	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Upper respiratory tract infection	1/11 (9.1%)		0/25 (0%)		1/11 (9.1%)		1/22 (4.5%)
Viral infection	0/11 (0%)		1/25 (4%)		1/11 (9.1%)		0/22 (0%)
Viral upper respiratory tract infection	0/11 (0%)		1/25 (4%)		1/11 (9.1%)		1/22 (4.5%)
Vulvovaginal mycotic infection	0/11 (0%)		1/25 (4%)		0/11 (0%)		1/22 (4.5%)
Bronchitis	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		1/22 (4.5%)
Gastroenteritis viral	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		1/22 (4.5%)
Nasopharyngitis	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Oral candidiasis	0/11 (0%)		0/25 (0%)		2/11 (18.2%)		0/22 (0%)
Oral herpes	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Pelvic abscess	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Pelvic infection	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Pneumonia	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Pyelonephritis	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Urinary tract infection	0/11 (0%)		0/25 (0%)		2/11 (18.2%)		3/22 (13.6%)
Urinary tract infection bacterial	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Urinary tract infection staphylococcal	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Vaginitis bacterial	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Injury, poisoning and procedural complications
Burns first degree	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Femur fracture	1/11 (9.1%)		0/25 (0%)		0/11 (0%)		0/22 (0%)
Arthropod bite	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Foot fracture	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Laceration	0/11 (0%)		0/25 (0%)		0/11 (0%)		2/22 (9.1%)
Ligament sprain	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Procedural pain	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Investigations
Blood potassium decreased	0/11 (0%)		1/25 (4%)		0/11 (0%)		2/22 (9.1%)
Blood pressure diastolic increased	1/11 (9.1%)		0/25 (0%)		0/11 (0%)		0/22 (0%)
Blood pressure increased	1/11 (9.1%)		0/25 (0%)		0/11 (0%)		0/22 (0%)
False positive investigation result	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
International normalised ratio increased	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Liver function test abnormal	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Occult blood positive	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Weight increased	2/11 (18.2%)		5/25 (20%)		0/11 (0%)		1/22 (4.5%)
Blood creatinine increased	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Blood phosphorus decreased	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Computerised tomogram thorax abnormal	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Glycosylated haemoglobin increased	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Haematocrit decreased	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Percussion test abnormal	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Metabolism and nutrition disorders
Fluid retention	0/11 (0%)		2/25 (8%)		0/11 (0%)		1/22 (4.5%)
Glucose tolerance impaired	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Hypokalaemia	1/11 (9.1%)		1/25 (4%)		1/11 (9.1%)		1/22 (4.5%)
Musculoskeletal and connective tissue disorders
Back pain	0/11 (0%)		2/25 (8%)		0/11 (0%)		1/22 (4.5%)
Arthralgia	0/11 (0%)		0/25 (0%)		0/11 (0%)		3/22 (13.6%)
Flank pain	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Joint swelling	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Myalgia	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Osteopenia	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Pain in extremity	0/11 (0%)		1/25 (4%)		0/11 (0%)		1/22 (4.5%)
Synovitis	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Systemic lupus erythematosus	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Nervous system disorders
Dizziness	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Headache	2/11 (18.2%)		1/25 (4%)		1/11 (9.1%)		2/22 (9.1%)
Sciatica	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Dysgeusia	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Hypoaesthesia	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Lethargy	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Migraine	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Polyneuropathy	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Tremor	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Psychiatric disorders
Anxiety	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Mood swings	0/11 (0%)		2/25 (8%)		0/11 (0%)		1/22 (4.5%)
Nervousness	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Abnormal behaviour	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Insomnia	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Renal and urinary disorders
Dysuria	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Nephrolithiasis	0/11 (0%)		0/25 (0%)		0/11 (0%)		2/22 (9.1%)
Reproductive system and breast disorders
Vulvovaginal discomfort	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Haemorrhagic ovarian cyst	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Cough	1/11 (9.1%)		1/25 (4%)		0/11 (0%)		1/22 (4.5%)
Pharyngeal erythema	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Pleural rub	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Pleuritic pain	0/11 (0%)		0/25 (0%)		2/11 (18.2%)		2/22 (9.1%)
Oropharyngeal pain	0/11 (0%)		2/25 (8%)		0/11 (0%)		0/22 (0%)
Skin and subcutaneous tissue disorders
Increased tendency to bruise	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Pruritus	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Rash	0/11 (0%)		0/25 (0%)		0/11 (0%)		1/22 (4.5%)
Blister	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Hypertrichosis	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Photosensitivity reaction	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Rash papular	0/11 (0%)		1/25 (4%)		0/11 (0%)		0/22 (0%)
Vascular disorders
Extremity necrosis	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)
Hypertension	1/11 (9.1%)		0/25 (0%)		1/11 (9.1%)		1/22 (4.5%)
Phlebitis	0/11 (0%)		0/25 (0%)		1/11 (9.1%)		0/22 (0%)

Limitations/Caveats

Non-serious adverse events (AEs) were not tabulated separately for these legacy results, so all treatment emergent adverse events are listed, and serious adverse events might be included.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.