Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01753401 |
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Recruitment Status :
Completed
First Posted : December 20, 2012
Results First Posted : February 27, 2020
Last Update Posted : February 27, 2020
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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 Type : | Interventional (Clinical Trial) |
| 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 : | January 2013 |
| Actual Primary Completion Date : | October 2015 |
| Actual Study Completion Date : | October 2015 |
| Arm | Intervention/treatment |
|---|---|
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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.
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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:
Drug: Placebo Placebo contains the same inactive ingredients as Acthar, and is given by SC injection
Other Name: 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 Name: Prednisone or equivalent |
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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:
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 Name: 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 Name: 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 Name: 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:
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 Name: Prednisone or equivalent |
- Number of Participants Who Meet the Definition of a Responder Within 4 Weeks [ Time Frame: 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.
- Number of Participants Who Meet the Definition of a Responder Within 8 Weeks [ Time Frame: 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
- Score on the SELENA-SLEDAI Within 8 Weeks [ Time Frame: 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
- BILAG Total Score Within 8 Weeks [ Time Frame: 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
- Physician's Global Assessment (PGA) of Disease Severity at Baseline [ Time Frame: 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.
- Physician's Global Assessment (PGA) of Disease Severity at Week 4 [ Time Frame: 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.
- Physician's Global Assessment (PGA) of Disease Severity at Week 8 [ Time Frame: 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.
- Number of Tender or Swollen Joints Within 8 Weeks [ Time Frame: 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
- Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Within 8 Weeks [ Time Frame: 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
- Krupp Fatigue Severity Score (FSS) Within 8 Weeks [ Time Frame: 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
- Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks [ Time Frame: 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
- Mean Score on the Mental Component Scale (MCS) of the Short Form 36 Health Status Questionnaire (SF-36) Within 8 Weeks [ Time Frame: 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.
- Number of Participants Who Meet the Definition of a Responder at Week 52 [ Time Frame: 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
- Score on the SELENA-SLEDAI at Week 52 [ Time Frame: 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.
- Physician's Global Assessment (PGA) of Disease Severity at Week 52 [ Time Frame: 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.
- Number of Tender or Swollen Joints at Week 52 [ Time Frame: at Week 52 ]The doctor counted the number of tender or swollen joints at Week 52.
- Cutaneous Lupus Activity as Measured by the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) at Week 52 [ Time Frame: 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.
- Krupp Fatigue Severity Score (FSS) at Week 52 [ Time Frame: 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).
- Mean Score on the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52 [ Time Frame: 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.
- Mean Score on the Mental Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) at Week 52 [ Time Frame: 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.
- Number of Participants With a Relapse Within 52 Weeks [ Time Frame: within 52 weeks ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| 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
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History of using certain medications prior to screening:
- oral prednisone (or equivalent) > 30 mg/day, any steroid injection, cyclosporine, or non-biologic investigational drug within 3 months prior to screening
- intravenous immunoglobulin (IVIg) or plasmapheresis within 4 months prior to screening
- cyclophosphamide within 6 months prior to screening; and/or
- B-cell targeted therapy, abatacept, or any biologic investigational agent within 12 months prior to screening
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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
- For the purposes of this study, osteoporosis is defined as evidence of vertebral or long bone fracture or vertebral T-score > 2.0
- For the purposes of this study, history of peptic ulcer is defined as ≤ 6 months prior to screening
- For the purposes of this study, congestive heart failure is defined as New York Heart Association Functional Class III-IV
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01753401
| United States, Arkansas | |
| Mallinckrodt Investigational Site | |
| Jonesboro, Arkansas, United States, 72401 | |
| United States, California | |
| Mallinckrodt Investigational Site | |
| La Jolla, California, United States, 92037 | |
| Mallinckrodt Investigational Site | |
| La Palma, California, United States, 90623 | |
| Mallinckrodt Investigational Site | |
| Long Beach, California, United States, 90806 | |
| Mallinckrodt Investigational Site | |
| Upland, California, United States, 91786 | |
| United States, Florida | |
| Mallinckrodt Investigational Site | |
| Brandon, Florida, United States, 33511 | |
| Mallinckrodt Investigational Site | |
| Clearwater, Florida, United States, 33765 | |
| Mallinckrodt Investigational Site | |
| Miami Lakes, Florida, United States, 33014 | |
| Mallinckrodt Investigational Site | |
| Orlando, Florida, United States, 32806 | |
| Mallinckrodt Investigational Site | |
| Tampa, Florida, United States, 33614 | |
| United States, Indiana | |
| Mallinckrodt Investigational Site | |
| Granger, Indiana, United States, 46530 | |
| United States, Louisiana | |
| Mallinckrodt Investigational Site | |
| Baton Rouge, Louisiana, United States, 70809 | |
| United States, Michigan | |
| Mallinckrodt Investigational Site | |
| Lansing, Michigan, United States, 48910 | |
| Mallinckrodt Investigational Site | |
| Lansing, Michigan, United States, 48917 | |
| United States, New York | |
| Mallinckrodt Investigational Site | |
| Brooklyn, New York, United States, 11201 | |
| Mallinckrodt Investigational Site | |
| Great Neck, New York, United States, 11020 | |
| Mallinckrodt Investigational Site | |
| New York, New York, United States, 10016 | |
| United States, North Carolina | |
| Mallinckrodt Investigational Site | |
| Charlotte, North Carolina, United States, 28210 | |
| United States, Pennsylvania | |
| Mallinckrodt Investigational Site | |
| Hershey, Pennsylvania, United States, 17033 | |
| Mallinckrodt Investigational Site | |
| Wyomissing, Pennsylvania, United States, 19610 | |
| United States, Texas | |
| Mallinckrodt Investigational Site | |
| Houston, Texas, United States, 77004 | |
| Mallinckrodt Investigational Site | |
| Houston, Texas, United States, 77034 | |
| Study Director: | Global Clinical Leader | Mallinckrodt |
| Responsible Party: | Mallinckrodt |
| ClinicalTrials.gov Identifier: | NCT01753401 |
| Other Study ID Numbers: |
QSC01-SLE-01 |
| First Posted: | December 20, 2012 Key Record Dates |
| Results First Posted: | February 27, 2020 |
| Last Update Posted: | February 27, 2020 |
| Last Verified: | August 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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SLE Lupus |
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Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Prednisone Adrenocorticotropic Hormone Anti-Inflammatory Agents |
Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Antineoplastic Agents |