Acthar Gel for Active Systemic Lupus Erythematosus (SLE)

A Multicenter, Randomized, Double Blind, Placebo Controlled Study to Assess the Efficacy and Safety of Acthar Gel in Subjects With Persistently Active Systemic Lupus Erythematosus Despite Moderate Dose Corticosteroids

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

Study Overview

• Status: Completed
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Drug: Acthar Gel; Drug: Placebo Gel

Detailed Description

This trial was initiated (started recruiting) in October 2016, but first patient was not enrolled (randomized) until December, 2016.

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1046AAQ
    • Aprillus Asistencia e Investigación
  • Buenos Aires, Argentina, C1111AAL
    • Consultorios Médicos Dr. Catalán Pellet
  • Tucumán, Argentina, T4000AXL
    • Centro Medico Privado de Reumatologia
• Chile
  • Santiago, Chile, 7500710
    • BioMedica Research Group
• Mexico
  • Aguascalientes, Mexico, 20010
    • IBIOMED Research Unit Aguascalientes
  • Boca Del Río, Mexico, 94290
    • Centro Especializado en Investigación Clínica
  • Ciudad de mexico, Mexico, 06090
    • Unidad de Investigacion de las Enfermedades Reumaticas
  • Cuautitlan Izcalli, Mexico, 54769
    • Phylasis Clinicas Research S de RL de CV
  • Durango, Mexico, 34000
    • Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
  • Mexico, Mexico, 44160
    • Centro Integral de Reumatologia
  • Monterrey, Mexico, 64000
    • Accelerium Clinical Research
  • Monterrey, Mexico, 64620
    • Centro de Estudios Clínicos y Especialidades Médicas
  • Mérida, Mexico, 97000
    • Centro Peninsular de Investigación Clínica S.C.P.
  • Mérida, Mexico, 97070
    • Köhler and Milstein Research
  • México, Mexico, 07760
    • Consultorio de Reumatologia
  • Queretaro, Mexico, 76090
    • SMIQ
  • San Luis Potosí, Mexico, 78213
    • Centro de Alta Especialidad en Reumatologia e Investigación del Potosí, SC
  • Zapopan, Mexico, 45030
    • Investigacion Biomedica para el Desarrollo de Fármacos S.A. de C.V.
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
• Peru
  • Lima, Peru
    • Investigaciones Clinicas S.A.C. del Instituto de Ginecologia y Reproduccion
  • San Borja, Peru, 15036
    • Clinica Vesalio
  • San Juan De Miraflores, Peru, 15801
    • Hospital de Apoyo Maria Auxiliadora
  • San Martin De Porres, Peru, 15102
    • Hospital Nacional Cayetano Heredia
• United States
  • California
    • Hemet, California, United States, 92543
      • C.V. Mehta MD Medical Corporation
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials
  • Florida
    • Fort Lauderdale, Florida, United States, 33309
      • Center for Rheumatology Immunology and Arthritis
    • Miami, Florida, United States, 33015
      • San Marcus Research Clinic
    • Miami, Florida, United States, 33147
      • Advanced Pharma Cr
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Office of George Timothy Kelly MD
  • New York
    • New York, New York, United States, 10032
      • NewYork-Presbyterian Columbia University Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • DJL Clinical Research
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research & Consulting
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Arthritis & Rheumatology Center of Oklahoma
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Physicians' Alliance
    • Memphis, Tennessee, United States, 38119
      • Office of Ramesh C. Gupta, MD
  • Texas
    • Houston, Texas, United States, 77034
      • Accurate Clinical Research
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acthar Gel; Participants receive Acthar Gel every other day for 4 weeks, and then twice per week for 20 weeks	Drug: Acthar Gel; 1 mL (80 Units) given by a shot under the skin (via subcutaneous injection); Other Names: Repository corticotropin
PLACEBO_COMPARATOR: Placebo Gel; Participants receive Placebo Gel every other day for 4 weeks, and then twice per week for 20 weeks	Drug: Placebo Gel; 1 mL (0 Units) given by a shot under the skin (via subcutaneous injection); Other Names: Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 16, Week 24
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.	Baseline, Week 16, Week 24
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.	Week 16, Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 16
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.	at Baseline and Weeks 4, 8, and 16
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.	at Baseline and at Weeks 4, 8, 12 and 16
Number of Participants With Decrease in Prednisone Dose to < 7.5 mg/Day at Week 20 and Week 24		Week 20, Week 24

Collaborators and Investigators

• Sponsor: Mallinckrodt

Publications and helpful links

General Publications

• Askanase AD, Wright D, Zhao E, Zhu J, Bilyk R, Furie RA. Post Hoc Biomarker Analyses from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Repository Corticotropin Injection (Acthar(R) Gel) for Persistently Active Systemic Lupus Erythematosus. Rheumatol Ther. 2021 Dec;8(4):1871-1886. doi: 10.1007/s40744-021-00351-7. Epub 2021 Sep 3.
• Askanase AD, Wan GJ, Panaccio MP, Zhao E, Zhu J, Bilyk R, Furie RA. Patient-Reported Outcomes from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Repository Corticotropin Injection (Acthar(R) Gel) for Persistently Active Systemic Lupus Erythematosus. Rheumatol Ther. 2021 Mar;8(1):573-584. doi: 10.1007/s40744-021-00294-z. Epub 2021 Mar 9.
• Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
• Askanase AD, Zhao E, Zhu J, Bilyk R, Furie RA. Repository Corticotropin Injection for Persistently Active Systemic Lupus Erythematosus: Results from a Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Rheumatol Ther. 2020 Dec;7(4):893-908. doi: 10.1007/s40744-020-00236-1. Epub 2020 Sep 29. Erratum In: Rheumatol Ther. 2021 Dec;8(4):1915.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 16, 2016
• Primary Completion (ACTUAL): July 31, 2019
• Study Completion (ACTUAL): October 25, 2019

Study Registration Dates

• First Submitted: November 1, 2016
• First Submitted That Met QC Criteria: November 1, 2016
• First Posted (ESTIMATE): November 3, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone
• Other Study ID Numbers: MNK14304067

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No