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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| corticotrophin 80 units | Active Comparator | Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) weekly |
|
| corticotrophin 80 units twice a week | Active Comparator | Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) twice a week |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| corticotrophin 80 units | Drug | 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 |
| 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 |
| 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 |
| 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. |
Inclusion Criteria:
Exclusion criteria:
Patients who have a diagnosis of any other inflammatory arthritis (e.g., psoriatic arthritis or ankylosing spondylitis).
Patients with exposure to any disease modifying antirheumatic drug (DMARD), Biologic, Non-biologic or experimental medication for the treatment of rheumatoid arthritis (RA).
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).
Patients with history of an infected joint prosthesis at any time with that prosthesis still in situ.
Patients have received prohibited medication:
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.
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.
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.
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).
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
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| Name | Affiliation | Role |
|---|---|---|
| Norman B Gaylis, MD | AARDS Research, Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AARDS Research, Inc | Aventura | Florida | 33180 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1 | Ten (10) Patients were treated with 80 U of ACTH once weekly and MTX 12.5-25 mg/week for a period of 6 months. Eight (8) Patients completed the 6 month trial in this group |
| FG001 | Group 2 | Ten (10) patients were treated with 80 U of ACTH twice a week and MTX 12.5-25 mg/week for a 6 month period. Nine (9) patients completed the trial in this group over the 6 month period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Corticotrophin 80 Units | Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) weekly 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 |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2 | Posted | Count of Participants | Participants | Baseline, Month 3 and Month 6 |
all adverse events were collected from the date of signing Informed Consent and Discontinuation or Completion of the trial. There were no adverse events either serious or non-serious to be reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 | Ten (10) Patients were treated with 80 U of ACTH once weekly and MTX 12.5-25 mg/week for a period of 6 months. Eight (8) Patients completed the 6 month trial in this group |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joanne Sagliani | Arthritis & Rheumatic Disease Specialties | 3059324162 | drnbg@rheum-care.com |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D000324 | Adrenocorticotropic Hormone |
| ID | Term |
|---|---|
| D053486 | Melanocortins |
| D011333 | Pro-Opiomelanocortin |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
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|
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 |
| Month 6 |
| Corticotrophin 80 Units Twice a Week |
Ten (10) patients will receive 80 units of corticotrophin Subcutaneous (SC) twice a week 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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Group 1 | Ten (10) Patients were treated with 80 U of ACTH once weekly and MTX 12.5-25 mg/week for a period of 6 months. Eight (8) Patients completed the 6 month trial in this group |
| OG001 | Group 2 | Ten (10) patients were treated with 80 U of ACTH twice a week and MTX 12.5-25 mg/week for a 6 month period. Nine (9) patients completed the trial in this group over the 6 month period. |
|
|
| Secondary | 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) | Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2 | Posted | Number | participants | Baseline, 3 months, 6 months |
|
|
|
| Secondary | 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). | Total number of Patients with erosions who completed 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2 | Posted | Number | participants | Month 3 and Month 6 |
|
|
|
| Secondary | 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 | Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2 | Posted | Number | participants | Month 6 |
|
|
|
| Other Pre-specified | 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. | Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2 | Posted | Count of Participants | Participants | Month 6 |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Group 2 | Ten (10) patients were treated with 80 U of ACTH twice a week and MTX 12.5-25 mg/week for a 6 month period. Nine (9) patients completed the trial in this group over the 6 month period. | 0 | 10 | 0 | 10 |
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| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| moderate disease activity |
|
| high disease activity |
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| moderate disease activity |
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| high disease activity |
|
| Baseline : erosions |
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| Month 3 : synovitis |
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| Month 3 : osteitis |
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| Month 3 : erosions |
|
| Month 6 : synovitis |
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| Month 6 : osteitis |
|
| Month 6 : erosions |
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| Month 6 : Progressed erosions |
|
| Month 6 : Regressed erosions |
|
| ESR Values |
|