Lupus Erythematosus, Systemic
Conditions
Brief summary
This trial is to study Acthar Gel in participants with active systemic lupus erythematosus (SLE). The doctor will assign eligible patients to one of two groups (like flipping a coin). Participants will receive the treatment assigned to their group for 24 weeks: * Acthar Gel * Placebo Gel, which looks like Acthar Gel, but has no medicine in it. The doctor or his staff will take measurements and ask questions to: * see how well the gel is working * see how safe it is for patients with SLE
Detailed description
This trial was initiated (started recruiting) in October 2016, but first patient was not enrolled (randomized) until December, 2016.
Interventions
DRUGActhar Gel
1 mL (80 Units) given by a shot under the skin (via subcutaneous injection)
DRUGPlacebo Gel
1 mL (0 Units) given by a shot under the skin (via subcutaneous injection)
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible to participate in this trial, a patient must: * Have a diagnosis of SLE according to 4 of the American College of Rheumatology revised criteria * Have active SLE * Have moderate to severe rash and/or arthritis as demonstrated by BILAG-2004 score A or B in the mucocutaneous and/or musculoskeletal body systems at both Screening and Randomization Visits * Have a documented history or screening result of 1. positive antinuclear antibody (ANA), OR 2. elevated anti-dsDNA or extractable nuclear antigen (ENA) antibodies * Have been on prednisone (or prednisone equivalent) before the screening visit: 1. at least 8 weeks, and 2. at a stable dose of 7.5 mg to 30 mg for at least 4 weeks
Exclusion criteria
A patient is not eligible to participate if he/she: * Has a history of sensitivity to adrenocorticotropic hormone (ACTH) preparations or porcine products * Has active lupus nephritis * Has active central nervous system (CNS) manifestations of SLE
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physician's Global Assessment (PGA) | Baseline, Week 16, Week 24 | PGA is a 100 mm visual analogue scale where higher scores indicate more severe disease activity. Lower scores indicate improvement. |
| British Isles Lupus Assessment Group 2004 (BILAG 2004) | Baseline, Week 16, Week 24 | BILAG records disease activity occurring over the past 4 weeks, and is used to determine whether different course of treatment is required. The BILAG-2004 index covers 97 signs/symptoms across 9 organ systems. Each question is answered as 0-not present, 1-improving, 2-same, 3-worse, or 4-new. The BILAG-2004 index categorizes disease activity in each organ system into five different levels from A to E. Grade A represents very active disease, Grade B represents moderate disease activity, Grade C indicates mild stable disease, and grade D implies no disease activity, but suggests the organ system had previously been affected. Grade E indicates no current or previous disease activity. A score is applied to each grade of each organ system using coding scheme of A=12, B=8, C=1, and D/E=0 and is summarized as a total score ranging 0-108. Higher scores indicate more severe disease activity. |
| Number of Participants With at Least a 4 Point Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) | Week 16, Week 24 | The SLEDAI-2K is a modified version of a composite score based on the presence or absence of clinical signs, clinical symptoms, and immunologic laboratory results taken within 10 days of the evaluations. Each of the descriptors has a weighted score and the total score of SLEDAI-2K is the sum of all 24 descriptor scores. The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity. Decrease from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severe Flare, Based on the SELENA Flare Index (SFI) at Week 16 | Week 16 | Among some adults, having a period of SLE symptoms-called flares-may happen every so often, sometimes even years apart, and go away at other times-called remission. The SFI categorizes SLE flares as mild, moderate or severe. |
| Number of Participants With Decrease in Prednisone Dose to < 7.5 mg/Day at Week 20 and Week 24 | Week 20, Week 24 | — |
| Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | at Baseline and Weeks 4, 8, and 16 | The CLASI total activity score reflects ongoing inflammation that can be treated, with points given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Mild, moderate, and severe disease correspond with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Higher scores indicate more disease activity, lower scores indicate improvement. |
| Mean Number of Swollen or Tender Joints on the 28-Joint Count | at Baseline and at Weeks 4, 8, 12 and 16 | The 28 Joint Count includes assessment of swelling and tenderness in the shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and knees. The investigator counts how many of the 28 joints are swollen or tender at the given week. |
Countries
Argentina, Chile, Mexico, Peru, United States
Participant flow
Pre-assignment details
Of 293 who signed informed consent, 172 were randomized into treatment groups
Participants by arm
| Arm | Count |
|---|---|
| Placebo Gel Participants receive Placebo Gel every other day for 4 weeks, and then twice per week for 20 weeks
Placebo Gel: 1 mL (0 Units) given by a shot under the skin (via subcutaneous injection) | 86 |
| Acthar Gel Participants receive Acthar Gel every other day for 4 weeks, and then twice per week for 20 weeks
Acthar Gel: 1 mL (80 Units) given by a shot under the skin (via subcutaneous injection) | 86 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Change of address | 0 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | No improvement | 0 | 1 |
| Overall Study | Out of state for indeterminate time | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Progressive Disease | 5 | 1 |
| Overall Study | Refused follow-up visit | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Placebo Gel | Acthar Gel | Total |
|---|---|---|---|
| Age, Continuous | 39.3 years STANDARD_DEVIATION 12.99 | 40.1 years STANDARD_DEVIATION 12.45 | 39.7 years STANDARD_DEVIATION 12.69 |
| Race (NIH/OMB) American Indian or Alaska Native | 19 Participants | 19 Participants | 38 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 9 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 29 Participants | 25 Participants | 54 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 33 Participants | 63 Participants |
| Sex: Female, Male Female | 82 Participants | 76 Participants | 158 Participants |
| Sex: Female, Male Male | 4 Participants | 10 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 86 | 0 / 86 |
| other Total, other adverse events | 23 / 86 | 31 / 86 |
| serious Total, serious adverse events | 8 / 86 | 4 / 86 |
Outcome results
Primary
British Isles Lupus Assessment Group 2004 (BILAG 2004)
BILAG records disease activity occurring over the past 4 weeks, and is used to determine whether different course of treatment is required. The BILAG-2004 index covers 97 signs/symptoms across 9 organ systems. Each question is answered as 0-not present, 1-improving, 2-same, 3-worse, or 4-new. The BILAG-2004 index categorizes disease activity in each organ system into five different levels from A to E. Grade A represents very active disease, Grade B represents moderate disease activity, Grade C indicates mild stable disease, and grade D implies no disease activity, but suggests the organ system had previously been affected. Grade E indicates no current or previous disease activity. A score is applied to each grade of each organ system using coding scheme of A=12, B=8, C=1, and D/E=0 and is summarized as a total score ranging 0-108. Higher scores indicate more severe disease activity.
Time frame: Baseline, Week 16, Week 24
Population: mITT population with a score at the given week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Gel | British Isles Lupus Assessment Group 2004 (BILAG 2004) | Baseline | 18.2 score on a scale | Standard Deviation 5.15 |
| Placebo Gel | British Isles Lupus Assessment Group 2004 (BILAG 2004) | Week 16 | 9.7 score on a scale | Standard Deviation 6.57 |
| Placebo Gel | British Isles Lupus Assessment Group 2004 (BILAG 2004) | Week 24 | 8.0 score on a scale | Standard Deviation 6.21 |
| Acthar Gel | British Isles Lupus Assessment Group 2004 (BILAG 2004) | Baseline | 18.0 score on a scale | Standard Deviation 5.45 |
| Acthar Gel | British Isles Lupus Assessment Group 2004 (BILAG 2004) | Week 16 | 7.7 score on a scale | Standard Deviation 5.91 |
| Acthar Gel | British Isles Lupus Assessment Group 2004 (BILAG 2004) | Week 24 | 6.9 score on a scale | Standard Deviation 5.87 |
Primary
Number of Participants With at Least a 4 Point Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K)
The SLEDAI-2K is a modified version of a composite score based on the presence or absence of clinical signs, clinical symptoms, and immunologic laboratory results taken within 10 days of the evaluations. Each of the descriptors has a weighted score and the total score of SLEDAI-2K is the sum of all 24 descriptor scores. The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity. Decrease from baseline indicates improvement.
Time frame: Week 16, Week 24
Population: modified Intent to Treat (mITT)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Gel | Number of Participants With at Least a 4 Point Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) | Week 16 | 40 Participants |
| Placebo Gel | Number of Participants With at Least a 4 Point Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) | Week 24 | 46 Participants |
| Acthar Gel | Number of Participants With at Least a 4 Point Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) | Week 16 | 41 Participants |
| Acthar Gel | Number of Participants With at Least a 4 Point Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) | Week 24 | 44 Participants |
Primary
Physician's Global Assessment (PGA)
PGA is a 100 mm visual analogue scale where higher scores indicate more severe disease activity. Lower scores indicate improvement.
Time frame: Baseline, Week 16, Week 24
Population: mITT population with score at the given week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Gel | Physician's Global Assessment (PGA) | Baseline | 58.8 score on a scale | Standard Deviation 15.81 |
| Placebo Gel | Physician's Global Assessment (PGA) | Week 16 | 33.2 score on a scale | Standard Deviation 18.77 |
| Placebo Gel | Physician's Global Assessment (PGA) | Week 24 | 26.9 score on a scale | Standard Deviation 17.76 |
| Acthar Gel | Physician's Global Assessment (PGA) | Baseline | 60.6 score on a scale | Standard Deviation 16.69 |
| Acthar Gel | Physician's Global Assessment (PGA) | Week 16 | 30.2 score on a scale | Standard Deviation 14.89 |
| Acthar Gel | Physician's Global Assessment (PGA) | Week 24 | 25.5 score on a scale | Standard Deviation 17.22 |
Secondary
Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score
The CLASI total activity score reflects ongoing inflammation that can be treated, with points given for the presence of erythema, scale, mucous membrane lesions, recent hair loss, and inflammatory alopecia. Mild, moderate, and severe disease correspond with CLASI activity score ranges of 0 to 9, 10 to 20, and 21 to 70, respectively. Higher scores indicate more disease activity, lower scores indicate improvement.
Time frame: at Baseline and Weeks 4, 8, and 16
Population: mITT population with scores at the given week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Week 4 | 5.8 score on a scale | Standard Deviation 5.57 |
| Placebo Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Week 12 | 4.5 score on a scale | Standard Deviation 5.41 |
| Placebo Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Week 8 | 5.0 score on a scale | Standard Deviation 5.19 |
| Placebo Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Week 16 | 3.8 score on a scale | Standard Deviation 4.36 |
| Placebo Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Baseline | 7.1 score on a scale | Standard Deviation 6.53 |
| Acthar Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Week 16 | 3.4 score on a scale | Standard Deviation 3.77 |
| Acthar Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Baseline | 7.9 score on a scale | Standard Deviation 7.48 |
| Acthar Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Week 4 | 5.6 score on a scale | Standard Deviation 5.3 |
| Acthar Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Week 8 | 5.0 score on a scale | Standard Deviation 5.41 |
| Acthar Gel | Mean Cutaneous Lupus Erythematosus Disease Area and Severity Score- Activity (CLASI) Total Activity Score | Week 12 | 4.0 score on a scale | Standard Deviation 4.08 |
Secondary
Mean Number of Swollen or Tender Joints on the 28-Joint Count
The 28 Joint Count includes assessment of swelling and tenderness in the shoulders, elbows, wrists, metacarpophalangeal joints, proximal interphalangeal joints and knees. The investigator counts how many of the 28 joints are swollen or tender at the given week.
Time frame: at Baseline and at Weeks 4, 8, 12 and 16
Population: mITT population with tender and swollen joints at the given week
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Week 4 | 4.9 Joints | Standard Deviation 4.77 |
| Placebo Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Week 12 | 2.9 Joints | Standard Deviation 4.4 |
| Placebo Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Week 8 | 3.8 Joints | Standard Deviation 4.97 |
| Placebo Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Week 16 | 2.8 Joints | Standard Deviation 3.67 |
| Placebo Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Baseline | 7.2 Joints | Standard Deviation 4.98 |
| Acthar Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Week 16 | 1.9 Joints | Standard Deviation 3.2 |
| Acthar Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Baseline | 8.2 Joints | Standard Deviation 5.85 |
| Acthar Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Week 4 | 4.2 Joints | Standard Deviation 4.24 |
| Acthar Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Week 8 | 2.9 Joints | Standard Deviation 3.42 |
| Acthar Gel | Mean Number of Swollen or Tender Joints on the 28-Joint Count | Week 12 | 2.3 Joints | Standard Deviation 3 |
Secondary
Number of Participants With Decrease in Prednisone Dose to < 7.5 mg/Day at Week 20 and Week 24
Time frame: Week 20, Week 24
Population: mITT Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Gel | Number of Participants With Decrease in Prednisone Dose to < 7.5 mg/Day at Week 20 and Week 24 | Week 20 | 5 Participants |
| Placebo Gel | Number of Participants With Decrease in Prednisone Dose to < 7.5 mg/Day at Week 20 and Week 24 | Week 24 | 6 Participants |
| Acthar Gel | Number of Participants With Decrease in Prednisone Dose to < 7.5 mg/Day at Week 20 and Week 24 | Week 20 | 3 Participants |
| Acthar Gel | Number of Participants With Decrease in Prednisone Dose to < 7.5 mg/Day at Week 20 and Week 24 | Week 24 | 4 Participants |
Secondary
Number of Participants With Severe Flare, Based on the SELENA Flare Index (SFI) at Week 16
Among some adults, having a period of SLE symptoms-called flares-may happen every so often, sometimes even years apart, and go away at other times-called remission. The SFI categorizes SLE flares as mild, moderate or severe.
Time frame: Week 16
Population: mITT population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Gel | Number of Participants With Severe Flare, Based on the SELENA Flare Index (SFI) at Week 16 | 3 Participants |
| Acthar Gel | Number of Participants With Severe Flare, Based on the SELENA Flare Index (SFI) at Week 16 | 0 Participants |