Acthar SLE (Systemic Lupus Erythematosus)

NCT02779153 | Withdrawn Phase 4

• 1 other identifier: 15-00295
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized study exploring the efficacy, safety and steroid sparing ability of two doses (40 U and 80 U) of Acthar in SLE patients with immune mediated hematologic manifestations requiring steroid use for a minimum of 2 weeks prior to screening.

Conditions

Systemic Lupus Erythematosus (SLE); Repository Corticotropin Injection

Keywords

SLE; H.P. Acthar Gel

Outcome Measures

Primary Outcomes (5)

• Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Score

  Disease activity is based on 24 questions, weighted across nine organ systems, combined into a total score that can range from 0 to 105, but are generally \< 20, even with very active disease.

  Baseline to Week 24

• British Isles Lupus Assessment Group (BILAG) disease activity index Score

  Items are rated as 0 (not present), 1 (improving), 2 (same), 3 (worse), or 4 (new) in the last 4 weeks compared with the previous 4 weeks. The numerical scores are used to categorize each organ system by an alphabetical score: 'A' reflecting severe disease requiring increases in prednisone to \> 20 mg daily and/or addition of immunosuppressive agents, 'B' indicated less active disease, requiring low-dose prednisone and/or symptomatic treatment with NSAIDs and/or antimalarials, 'C' reflecting mild disease requiring only symptomatic therapy, 'D' reflecting previous organ system involvement without current disease activity, and 'E' reflecting no prior or no current disease involvement in that organ system.

  Baseline to Week 24

• Physician's Global Assessment Score

  The Physician's Global Assessment is a 10 cm visual analogue scale (VAS) anchored at 0 (none) and 3 (severe) with intermediate lines at 1 (mild) and 2 (moderate). It is designed for the physician to indicate the patient's overall disease activity at a particular visit

  Baseline to Week 24

• SELENA Flare Index Score

  The SELENA Flare Index categorizes SLE flare as 'mild or moderate' or 'severe' based on six variables * Change in SLEDAI score from the most recent assessment to current. * Change in signs or symptoms of disease activity. * Change in prednisone dosage. * Use of new medication for disease activity or hospitalization. * Change in PGA score. * Hospitalization for SLE activity (severe flare only).

  Baseline to Week 24

• SLICC/ACR Damage Index

  The SLICC/ACR Damage Index measures irreversible organ damage from either the disease process or treatment, which has been present for ≥ 6 months, in 12 organ systems. It is an important predictor of long-term mortality and is an independent outcome measure separate from the SLEDAI.

  Baseline to Week 24

Secondary Outcomes (3)

• Medical Outcomes Survey Short Form-36

  Baseline to Week 24

• FACIT Fatigue Scale

  Baseline to Week 24

• Patient's Global Assessment

  Baseline to Week 24

Study Arms (2)

Acthar low dose (40 U)

EXPERIMENTAL

Drug: Acthar low dose (40 U)

Acthar high dose (80 U)

EXPERIMENTAL

Drug: Acthar high dose (80 U)

Interventions

Acthar low dose (40 U) DRUG

The 40U group will administer 0.5 mL of study medication once a day. Patients will taper study medication during Week 2 through the remainder of the study and will administer 0.5 mL of study medication twice a week. The stable Acthar regimen should be maintained for the remainder of the study. However, dose adjustments may be implemented if needed based on safety.

Also known as: Repository Corticotropin Injection

Acthar low dose (40 U)

Acthar high dose (80 U) DRUG

The 80U group will administer 1.0 mL of study medication every day. If a patient meets dose reduction criteria, their assigned volume will be adjusted from 1.0 mL to 0.5 mL. Patients will taper study medication during Week 2 through the remainder of the study. However, dose adjustments may be implemented if needed based on safety.

Also known as: Repository Corticotropin Injection

Acthar high dose (80 U)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent.
• Diagnosis of SLE according to the American College of Rheumatology revised criteria (fulfilled ≥ 4 criteria).
• Hematologic BILAG scores due to hemolytic anemia or thrombocytopenia of BILAG A (including hemolytic anemia with hemoglobin \< 8.0 g/dL or platelet count \< 25 x 109 l) or BILAG B (including hemolytic anemia with hemoglobin 8.0 - 9.9 g/dDL or platelet count 25 - 49 x 109 l) based on screening laboratory assessment.
• Currently taking prednisone ≥ 7.5 mg or equivalent for hematologic SLE for at least 2 weeks prior to screening.
• Use of antimalarials and NSAIDs (stable regimen within the 4 weeks prior to screening), as well as methotrexate, azathioprine, and mycophenolate mofetil (stable regimen within the 4 weeks prior to screening) are permitted but not required. If used, the regimen must remain stable through the study. An increase or addition of SLE medication at any time during the study is not permitted.
• Ability to comply with study procedures, which include SC injections of study medication, adhering to concomitant medication restrictions, and attending scheduled office visits.

You may not qualify if:

• Patients with a recent history (\< 2 week prior to screening) of starting prednisone or equivalent.
• 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.
• Patients with a history of concomitant medication use as follows:
• a. Receipt of the following within 1 month prior to screening: i. Any steroid injection (IM, intraarticular, or IV) b. Receipt of any of the following within 3 months prior to screening: i. Cyclosporine ii. Any non-biologic investigational drug c. Receipt of the following within 4 months prior to screening: i. IVIg ii. Plasmapheresis d. Receipt of cyclophosphamide within 6 months prior to screening e. Receipt of the following within 12 months prior to screening: i. B cell targeted therapy (rituximab or other anti-CD20 agent, anti-CD22 \[epratuzumab\], anti-CD52 \[alentuzumab\], or belimumab) ii. Abatacept iii. Any biologic investigational agent
• 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 lumbar spine T-score \> 2.0 standard deviations below the mean of the reference population.
• 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.
• For the purposes of this study, uncontrolled hypertension is defined as a mean systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg on ≥ 3 seated readings taken at least 5 minutes apart during the screening period.
• Reproductive status:
• Women who are pregnant,
• Women who are breastfeeding,
• Women of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period, as evaluated by the Investigator (women of non-childbearing potential are those that have a history of hysterectomy, bilateral oophorectomy, or are postmenopausal with no history of menstrual flow for ≥ 12 months prior to screening).
• Immune System: Known immunocompromised status (not related to SLE or therapies for SLE), including individuals who have undergone organ transplantation or who are known to be positive for the human immunodeficiency virus.

Sponsors & Collaborators

• NYU Langone Health: lead
• Mallinckrodt: collaborator

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Adrenocorticotropic Hormone

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Amit Saxena, MD

  New York University Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2016
• First Posted: May 20, 2016
• Study Start: October 1, 2016
• Primary Completion: May 22, 2019
• Study Completion: May 22, 2019
• Last Updated: September 13, 2019

Record last verified: 2019-09