Acthar in Treatment of Refractory Dermatomyositis and Polymyositis

August 2, 2017 updated by: Rohit Aggarwal, MD

Open Label Proof of Concept Study to Evaluate Efficacy and Safety of Adrenocorticotropic Hormone Gel in Refractory Dermatomyositis or Polymyositis

The purpose of this research study is to evaluate the effectiveness of the study drug, ACTH Gel in people diagnosed with dermatomyositis a disease that causes muscle weakness and is associated with a rash (DM) or polymyositis (PM) a disease that causes muscle weakness without a rash. The study doctors want to evaluate whether ACTH Gel will improve the symptoms of this disease. This drug is approved by the Food and Drug Administration (FDA) for dermatomyositis (DM) and polymyositis (PM). ACTH gel has been an FDA-approved treatment for myositis since 1952, and in 2010 the FDA retained PM and DM as diseases approved for ACTH gel use.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Despite its FDA approval there is very limited data on its clinical effectiveness in PM and DM. There was a recent study published in the peer-review journal Drug Design, Development and Therapy on a retrospective case series evaluating Acthar in the treatment of PM and DM. Acthar was administered to five patients who had previously failed multiple steroid and immunosuppressant treatment regimens. The patients received injections of Acthar over the course of 12 weeks or more. Improvement in PM and DM symptoms related to disease exacerbations was seen in all five patients. Symptom improvements included increased muscle strength, resolution of disease-related skin manifestations and improvements in the ability to perform tasks associated with daily living. All of these patients tolerated the treatment well with no significant side effects reported. The paper, "Treating refractory dermatomyositis or polymyositis with adrenocorticotropic hormone gel: a retrospective case series," was authored by Dr. Todd Levine, M.D., Co-Director of the Neurophysiology Department at Banner Good Samaritan Medical Center, Assistant Professor at the University of Arizona in Neurology, and Member of Phoenix Neurological Associates.

H.P. Acthar® Gel, or Acthar, is a prescription medication containing the hormone adrenocorticotropin (hormone produced and secreted by the anterior pituitary gland), also known as ACTH. H.P. Acthar Gel is a highly purified preparation of adrenocorticotropic hormone (ACTH) in a gel that is designed to provide extended release of the ACTH following injection. Acthar was originally approved by the FDA in 1952. It is approved for use in 19 different conditions including dermatomyositis and polymyositis.

Acthar is designed to provide a prolonged release of the medication after it is injected. Acthar is not a steroid; it works by helping your body produce its own natural steroid hormones, such as cortisol, corticosterone, and aldosterone. Acthar is an injection that is given intramuscularly (into the muscle). Subjects enrolled in the study will be asked to self administer Acthar two times per week. Subjects will be provided training by the principal investigator on how to perform the self injections.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Great Neck, New York, United States, 11021
        • North Shore LIJ Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15261
        • University of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Definite or probable polymyositis (PM) or dermatomyositis (DM) by Bohan and Peter criteria.
  • PM patients must either possess a myositis-associated autoantibody or undergo adjudication for confirmation of the PM diagnosis by consensus of two experts to ensure non-PM patients are not enrolled. This step is necessary since there are well-known mimics of PM.
  • Age ≥ 18 years.

  • Active myositis as defined by baseline Manual Muscle Testing (MMT-8) no greater than 125/150 and at least 2 additional CSM meeting the criteria stipulated below:

    1. Patient global with a minimum value of 2.0 cm on a 10 cm visual analog scale(VAS)
    2. Physician global with a minimum value of 2.0 cm on a 10 cm VAS scale
    3. Health Assessment Questionnaire (HAQ) disability index with a minimum value of 0.25
    4. Elevation of at least one of the muscle enzymes [which includes creatine kinase (CK), aldolase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] at a minimum level of 1.3 x the upper limit of normal.
    5. Global extramuscular disease activity score with a minimum value of 1.0 cm on a 10 cm VAS scale [this measure is the physician's composite evaluation and is based on assessments of activity scores on the constitutional, cutaneous, skeletal, gastrointestinal, pulmonary and cardiac scales of the Myositis Disease Activity Assessment Tool (MDAAT)].

  • To ensure that we can enroll active DM patients with a severe rash who may not meet the MMT-8 criterion noted above, we propose additional enrollment criteria such that the International Myositis Assessment and Clinical Studies (IMACS) definition of improvement (DOI) can potentially be met:

    1. Cutaneous VAS score on MDAAT > 3 cm on a 10 cm VAS scale, and
    2. At least 3 of the above 5 (a through e under 4.) criteria.
  • Refractory myositis is defined by active disease despite an adequate glucocorticoid trial (> 2 months of usual glucocorticoid therapy or intolerance to such therapy) and/or ≥ 1 conventional immunosuppressive agent (e.g. methotrexate, azathioprine, tacrolimus, cyclosporine, mycophenolate mofetil, IVIG, anti-TNF or rituximab) for a reasonable dose and duration (> 3 months or intolerance to therapy). It is recommended to enroll refractory patients failing (or intolerant to) both glucocorticoids and at least 1 conventional immunosuppressive agent.
  • If the enrolling physician is planning to continue current immunosuppressive agents or glucocorticoids as concomitant therapy with Acthar gel during the trial, then patient must be on a stable glucocorticoid and/or immunosuppressive dose 2 weeks prior to visit 1. The patient should have been on that immunosuppressive medication for at least 8 weeks (and at least 4 weeks for glucocorticoids) prior to visit 1.
  • If the enrolling physician is planning to discontinue current immunosuppressive agent or glucocorticoids, then following wash out period is required prior to visit 1.
  • If previous concomitant medications were discontinued, the following wash out periods are required prior to Visit 1
  • Methotrexate -4 weeks
  • Other IS agent (e.g. azathioprine, cyclosporine, tacrolimus, leflunomide, mycophenolate mofetil) - 4 weeks
  • IVIg or cyclophosphamide - 2 months
  • rituximab -6 months
  • infliximab or adalimumab -8 weeks
  • glucocorticoids - 2 weeks
  • etanercept -2 weeks
  • anakinra -1 week

Exclusion Criteria:

  • Juvenile DM or PM, myositis in overlap with another connective tissue disease, cancer associated myositis, inclusion body myositis, or any other non immune-mediated myopathy.
  • Hypersensitivity to Acthar
  • Severe cardiac or pulmonary involvement
  • Severe muscle damage defined as a baseline global muscle damage score on the MDI (Myositis Damage Index) of ≥ 5 cm on a 10 cm VAS.
  • Patients with malignancy within 3 years of screening (except basal cell cancer or squamous cell cancer of skin).
  • Uncontrolled diabetes, hepatic or renal disease.
  • Ongoing active or chronic infections.
  • Pregnant or lactating females.
  • For any medical or physical or socio-psychological reasons that PI feels would not allow the subject to complete the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Acthar Gel
Acthar Gel (Adrenocorticotropic Hormone Gel)in refractory PM and DM patients using an open label design for 6 months. We will enroll 10 active and refractory PM/DM patients over a 15 month period, followed by 6 months of additional follow-up for each subject. Study subjects will self-administer subcutaneously H.P. Acthar Gel 80 units (1 ml) twice a week for a period of six months. Outcome measures were not evaluated on subjects who did not reach the 8 week time point in the trial.
Drug: Adrenocorticotropic Hormone Gel
H.P. Acthar Gel 80 units will be self-administered subcutaneously twice weekly by the subject for a period of 6 months.
Other Names:
  • H.P. Acthar Gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Specific Aim 1: Number of Subjects Meeting IMACS Preliminary Definition of Improvement (DOI).
Time Frame: Primary end point: IMACS preliminary definition of improvement (DOI)
3 of any of the 6 core set measures (CSM) improved by ≥ 20%, with no more than 2 CSM worsening by ≥25% (worsening measure cannot include the MMT). The DOI should be met at least once on any of the 6 follow up visits and maintained until week 24. Subjects not meeting DOI during the trial are treatment failures.
Primary end point: IMACS preliminary definition of improvement (DOI)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Steroid-sparing Effect of H.P. Acthar Gel in Refractory Adult PM and DM Patients.
Time Frame: Steroid sparing effect and safety and tolerability at 24 weeks compared to baseline
Mean change in glucocorticoid dose (equivalent prednisone dose) at 24 weeks compared to baseline.
Steroid sparing effect and safety and tolerability at 24 weeks compared to baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rohit Aggarwal, MD

Collaborators

Mallinckrodt

Investigators

  • Principal Investigator: Rohit Aggarwal, MD, University of Pittsburgh, Division of Rheumatology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

September 1, 2015

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

July 5, 2013

First Submitted That Met QC Criteria

July 19, 2013

First Posted (Estimate)

July 24, 2013

Study Record Updates

Last Update Posted (Actual)

September 1, 2017

Last Update Submitted That Met QC Criteria

August 2, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRO13050507

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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