Efficacy, Radiographic and Laboratory Changes in Refractory Rheumatoid Arthritis Patients Treated With H.P. Acthar Gel

Open-label, Pilot Protocol of Patients With Rheumatoid Arthritis Who Were Treated With H.P. Acthar Gel After an Incomplete Response to Combinations of DMARDs and Biologic DMRADs

This study will examine the clinical response, cytokine expression and joint imaging after addition of Acthar Gel. The hypothesis is that H.P. Acthar Gel is both safe and effective for treatment of patients with refractory rheumatoid arthritis (RA) and has different mechanism of action than steroids and other DMARDs.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: H.P. Acthar gel

Detailed Description

Rheumatoid arthritis (RA) is a systemic inflammatory disease which causes premature mortality, disability and compromised quality of life in the industrialized and developing world. The prevalence of RA is believed to range from 0.5-1.0% in the general population. Over the past half century, many studies have found mortality to be increased in patients with established RA in comparison with the general population. Despite available treatment options for RA, some patients still have disease that is refractory to treatment and cannot achieve remission.

H.P. Acthar gel (adrenocorticotropic hormone gel) received FDA approval for treatment of a variety of diseases, including RA in 1952. The proposed efficacy of H.P. Acthar gel has been attributed to its ability to induce production of endogenous steroids and to bind melanocortin receptors on lymphocytes and other cells to modulate immunologic responses. The present study will examine the clinical response, cytokine production and joint imaging after addition of H.P. Acthar gel to confirm the efficacy, confirm different mechanism of action in comparison to steroids and other DMARDs by looking for post treatment changes in cytokine expression.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Iraj Sabahi, MD; Phone Number: 925-264-7100; Email: irajsabahi2015@gmail.com
• Study Contact Backup: Name: Sonia Dimas; Phone Number: 209-634-3898; Email: irajsabahi2015@gmail.com

Study Locations

• United States
  • California
    • Pleasanton, California, United States, 94588
      • Recruiting
      • Iraj Sabahi Research Inc
      • Contact: Iraj Sabahi, MD; Phone Number: 925-264-7100; Email: irajsabahi2015@gmail.com
      • Contact: Sonia Dimas; Phone Number: 209-634-3898; Email: irajsabahi2015@gmail.com
    • Turlock, California, United States, 95382
      • Recruiting
      • Iraj Sabahi Research Inc
      • Contact: Iraj Sabahi, MD; Phone Number: 925-264-7100; Email: irajsabahi2015@gmail.com
      • Contact: Sonia Dimas; Phone Number: 209-634-3898; Email: irajsabahi2015@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with diagnosis of RA with incomplete or failure to treatment described as either A or B A: Failure to achieve remission or low disease activity within 3 to 6 months of treatment with combination of methotrexate or other DMARDs therapy with a biologic DMARD in maximally tolerated doses within the usual therapeutic range.

   B- A requirement, in addition to DMARDs and biologic DMARDs, for chronic glucocorticoid therapy in a dose of greater than about 5 to 7.5 mg/day of prednisone or equivalent to achieve or maintain remission or low disease activity after 3 to 6 months of treatment.

2. Fluent in reading and writing in English language.
3. ≥ 21 years of age at the time of participation.

Exclusion Criteria:

1. Pregnancy
2. Presence if contraindications for treatment with H.P. Acthar gel including but not limited to any known history of scleroderma, osteoporosis, systemic fungal infections, ocular Herpes Simplex, recent administration of live or live attenuated vaccine (prior 6 months), recent surgery (prior 6 months), history of or the presence of a peptic ulcer, primary adrenocortical insufficiency, adrenal cortical hyperfunction; congestive heart failure (defined as New York Hear Association Functional Class I to IV, uncontrolled hypertension.
3. Previous use of ACTH preparations for treatment of nephrotic syndrome (including but not limited to H.P. Acthar gel and Synacthen®).
4. Previous history of sensitivity to ACTH preparations (including but not limited to H.P. Acthar gel and Synacthen®).
5. Previous history of sensitivity to porcine protein products.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group A; Will be receiving the same background medications and H.P. Acthar gel 40 units twice weekly for 12 weeks. Patients in group A, can be cross over to group B on week 13 if disease is uncontrolled for continuation until week 24. If their disease is under control then they will continue with the same dosage until week 24. If the disease is under control, then tapering the steroid dosage can be attempted at the principal investigation's discretion.	Drug: H.P. Acthar gel; H.P. Acthar gel in treatment of Refractory RA; Other Names: Repository Corticotropin Injection
ACTIVE_COMPARATOR: Group B; Will be receiving the same background medications and H.P. Acthar gel 80 units twice weekly for 12 weeks. if the disease is not under control, will continue with same dosage until week 24. If the disease is under control, will be given the option to reduce the dosage to 40 units twice weekly only if patient is suffering from H.P. Acthar gel related adverse effects. If the disease is under control, then tapering the steroid dosage can be attempted at the principal investigation's discretion.	Drug: H.P. Acthar gel; H.P. Acthar gel in treatment of Refractory RA; Other Names: Repository Corticotropin Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR 20 response ACR 20 response	Equal or greater than 20 % reduction in RA disease activity	Baseline to week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR 50 response	Equal or greater than 50 % reduction in RA disease activity	Baseline to week 24
ACR 70 response	Equal or greater than 70 % reduction in RA disease activity	Baseline to week 24
EULAR moderate response	Decline in the DAS 28 score by >1.2 (without reaching low disease activity) OR The decline of 0.6 to 1.2, plus reaching at least moderate disease activity (DAS28 <5.1).	Baseline to week 24
EULAR good response	Decline in DAS 28 score must exceed 1.2 and result in the achievement of low disease activity (DAS28 <3.2).	Baseline to week 24
Resolution of Powered Doppler Signal of MSKUS studies	Decline or resolution of synovitis detected in ultra sonographic examination of joints	Baseline to week 24
Resolution of signs of active inflammation in MRI	Decline or resolution of synovitis, tenosynovitis or bone edema detected in MRI examination of joints	Baseline to week 24
Reduction in Vectra DA Score	Decline in RA disease activity manifested as decline in Vectra DA Score	Baseline to week 24
Correlation between MSKUS and MRI Imaging findings	Comparison between MSKUS and MRI imaging	Baseline to week 24
Correlation between imaging findings and Vectra DA test	Comparison between MSKUS/MRI findings and Vectra DA test results	Baseline to week 24

Collaborators and Investigators

• Sponsor: Iraj Sabahi Research Inc.
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Iraj Sabahi, MD, Iraj Sabahi Research Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 3, 2017
• Primary Completion (ANTICIPATED): February 1, 2018
• Study Completion (ANTICIPATED): February 1, 2019

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (ACTUAL): March 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 17, 2017
• Last Update Submitted That Met QC Criteria: March 16, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone
• Other Study ID Numbers: IS2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No