The Effect of Corticotrophin (ACTH) in Combination With Methotrexate in Newly Diagnosed Rheumatoid Arthritis Patients

Study of The Effect of Corticotrophin in Combination With Methotrexate in Newly Diagnosed Rheumatoid Arthritis Patients From a Clinical and Structural Perspective As Measured by a Clinical Disease Activity Index Score and Bone Edema, Synovitis and Erosions on Magnetic Resonance Imaging

The purpose of the study is to evaluate the effect of the utilization of two doses of corticotrophin ( ACTH) as a treatment in patients with early onset rheumatoid arthritis as an alternative to conventional steroid therapy by evaluating the change from baseline in the clinical findings as well as the structural findings on Magnetic Resonance Imaging (MRI). Corticotrophin (ACTH) may prevent the well documented structural progression damage in RA patients using disease-modifying antirheumatic drug (DMARD) therapy alone.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: corticotrophin 80 units

Detailed Description

This is a Phase II 24-week open-label study to evaluate the efficacy and safety of H.P. Acthar Gel Respository Injection, Corticotrophin( ACTH) administered to newly diagnosed patients with rheumatoid arthritis in conjunction with methotrexate, folllowed by a 24 week follow-up period. There will be a total of twenty (20) patients and two (2) treatment groups with 10 patients in each treatment group

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Aventura, Florida, United States, 33180
      • AARDS Research, Inc

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:

1. Patient must be at least 18 years old at the screening visit.
2. Patient must be able to understand the information provided to them and to give written Informed Consent.
3. Female patients must be either postmenopausal for at least 1 year, surgically incapable of childbearing, or effectively practicing an acceptable method of contraception (oral/parenteral/implantable hormonal contraceptives, Intrauterine Device (IUD), or barrier and spermicide). Abstinence only is not an acceptable method. Patients must agree to use adequate contraception during the study and for 4 weeks after their last dose of corticotrophin (ACTH). Male patients must agree to ensure they or their female partner(s) are using adequate contraception during the study and for 4 weeks after the patient receives their last dose of corticotrophin (ACTH).
4. Patients must have a new diagnosis of adult-onset rheumatoid arthritis (RA) as defined by the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria and who have had symptoms for <1 year.
5. Patients must be experiencing mild to moderate rheumatoid arthritis ( RA), have at least 6 tender and 6 swollen joints at screening and a clinical disease activity index (CDAI) score of > 6.0
6. A Baseline Magnetic Resonance Imaging ( MRI) must show the presence of osteitis or erosions in the hand or wrist.
7. Patients must be able and willing to comply with the requirements of the study protocol.
8. Patients must have a C-reactive Protein (CRP) or erythrocyte sedimentation rate (ESR) > upper limits of normal

Exclusion criteria:

1. Patients who have a diagnosis of any other inflammatory arthritis (e.g., psoriatic arthritis or ankylosing spondylitis).
2. Patients with exposure to any disease modifying antirheumatic drug (DMARD), Biologic, Non-biologic or experimental medication for the treatment of rheumatoid arthritis (RA).
3. Patients with a non-inflammatory type of arthritis (e.g. osteoarthritis or fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of study drug on the patient's primary diagnosis of rheumatoid arthritis (RA).
4. Patients with history of an infected joint prosthesis at any time with that prosthesis still in situ.

5. Patients have received prohibited medication:

   • non-steroidal anti-inflammatory drug (NSAIDs /COX-2 inhibitors) (any change in dose regimen in the 7 days prior to baseline)
   • Oral corticosteroids within 4 weeks of baseline
   • Intra-muscular, intra-venous, intra-articular (IM/IV/IA) corticosteroids/ Intra-articular (IA) Hyaluronic acid (any dose 28 days prior to baseline)
6. Female patients who are breast-feeding, pregnant, or plan to become pregnant during the trial or within twelve weeks following last dose of study drug.
7. Patients with a history of chronic infection due to fungal, parasitic or mycotic pathogens during the preceding year, recent serious or life-threatening infection within 6 months (including herpes zoster), or any current sign or symptom that may indicate an infection.
8. Patients with active Tuberculosis (TB) (or history of active TB), positive chest X-ray for TB, or positive (defined as induration of ≥ 5mm) purified protein derivative (PPD) skin test, positive QuantiFERON, or patients having close contact with an individual with active TB. Patients having a PPD skin test ≥ 5 mm or a positive QuantiFERON test can enter the study, provided that active TB is excluded and provided that they are adequately treated for latent TB (e.g., isonicotinic acid hydrazide [INH therapy] for 9 months [with vitamin B6]) and provided that appropriate treatment is initiated simultaneously with the first administration of ACTH.
9. Patients at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and patients who are permanently bedridden or wheelchair bound).
10. Patients with a known allergy or intolerance to steroids 11 Concurrent malignancy or a history of malignancy (other than carcinoma of the cervix or basal cell carcinoma successfully treated more than 5 years prior to screening).

12. Patients with a current or recent history of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease.

13. Patients with class III or IV congestive heart failure according to the New York Heart Association (NYHA) 1964 classification criteria.

14. Patients with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).

15. Patients with any other condition (e.g. clinically significant laboratory values) which in the Investigator's judgment would make the patient unsuitable for inclusion in the study.

16. Patients who have a metal device affected by MRI (e.g., any type of electronic, mechanical, or magnetic implant; cardiac pacemaker; aneurysm clip(s); implanted cardioverter defibrillator; or a cochlear implant) 17. Patients who have a potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects) for which they have sought medical attention.

18. Concurrent steroid use for any concomitant disease. 19. Subjects who are known to be Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C positive

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: corticotrophin 80 units; Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) weekly	Drug: corticotrophin 80 units; Comparison of different dosages of the drug. Ten patients will receive 80 units of corticotrophin weekly. Ten patients will receive 80 units bi-weekly of corticotrophin; Other Names: Acthar, Corticotrophin, ACTH
Active Comparator: corticotrophin 80 units twice a week; Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) twice a week	Drug: corticotrophin 80 units; Comparison of different dosages of the drug. Ten patients will receive 80 units of corticotrophin weekly. Ten patients will receive 80 units bi-weekly of corticotrophin; Other Names: Acthar, Corticotrophin, ACTH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinical Disease Activity Index (CDAI) Score	To evaluate the effect of the use of 2 doses of corticotrophin (ACTH) as a treatment in patients with early onset rheumatoid arthritis as an alternative to conventional steroid therapy by evaluating the change from baseline in the clinical findings as measured by Clinical Disease Activity Index (CDAI) scores. The CDAI is calculated at the specified time points using the formula: CDAI = SJC(28) + TJC(28) + PGA + EGA SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) Interpretation: A lower CDAI score from Baseline would mean improvement in disease activity and an increase in CDAI score from Baseline would mean an increase in disease activity or a worsening in disease activity. Scores: 0.0-2.8 = Range for Remission; 2.9-10.0 = Range for Low disease activity; 10.1-22.0 Range for Moderate disease activity; 22.1-76 Range for High disease activity.Total range is from 0-100, with the high scores representing high disease activity.	Baseline, Month 3 and Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of MRI Structural Improvements	To compare the number of patients who have synovitis, oseitis and erosions at Baseline, Month 3 and Month 6. Normal range for synovitis, osteitis and erosions is zero (0)	Baseline, 3 months, 6 months
Number of Participants With Increased or Decreased Erosions of the Hand and Wrist	Comparison of the change in the number of erosions seen in the joints of the hand and wrist as measured by Magnetic Resonance Imaging (MRI) findings. Regression indicates improvement in the number of erosions seen from Baseline and Progression indicates worsening in the number of erosions seen from Baseline. Normal range is zero (0).	Month 3 and Month 6
Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings	Comparison of the clinical findings as measured by the Clinical Disease Activity Index (CDAI) versus the structural findings as measured by Magnetic Resonance Imaging (MRI). Improvement is measured as a reduction in CDAI score from Baseline to Month 6 and improvement in MRI is regression of erosions, oseitis and synovitis at month 6. Norman MRI score is zero (0). CDAI: 0.0-2.8 remission; 2.9-10.0 low disease activity; 10.1-22 moderate disease activity; 22.1-76 high disease activity. A decrease in CDAI score is improvement	Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR)	comparisons not statistical analysis will be made from Baseline and Month 6 of the C- reactive Protein (CRP) values and Erythrocyte Sedimentation Rate (ESR) to determine the number of patients whose test result improved or worsenedCRP value (normal range <1.0 mg/dl). ESR (normal range 0-28 mm/hr) . If the value is increased, the disease activity worsened. If the value is reduced the disease activity is improved.	Month 6

Collaborators and Investigators

• Sponsor: Gaylis, Norman B., M.D.
• Investigators: Principal Investigator: Norman B Gaylis, MD, AARDS Research, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: September 9, 2013
• First Submitted That Met QC Criteria: September 18, 2013
• First Posted (Estimate): September 23, 2013

Study Record Updates

• Last Update Posted (Actual): January 18, 2019
• Last Update Submitted That Met QC Criteria: January 17, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis
• 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: RA2013-01