Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis
Brief summary
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.
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
Interventions
DRUGcorticotrophin 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
Sponsors
Gaylis, Norman B., M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline, Month 3 and Month 6 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of MRI Structural Improvements | Baseline, 3 months, 6 months | 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) |
| Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 3 and Month 6 | 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). |
| Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings | Month 6 | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | Month 6 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 10 |
| 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 | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Corticotrophin 80 Units Twice a Week | Corticotrophin 80 Units | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 7 Participants | 14 Participants |
| Age, Continuous | 57 years | 60 years | 59 years |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
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.
Time frame: Baseline, Month 3 and Month 6
Population: Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline | remission | 0 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline | low disease activity | 0 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline | moderate disease activity | 0 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline | high disease activity | 9 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 3 | remission | 3 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 3 | low disease activity | 2 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 3 | moderate disease activity | 4 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 3 | high disease activity | 0 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 6 | remission | 2 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 6 | low disease activity | 4 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 6 | moderate disease activity | 2 Participants |
| Group 1 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 6 | high disease activity | 1 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 6 | moderate disease activity | 2 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline | remission | 0 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 3 | moderate disease activity | 2 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline | low disease activity | 0 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 6 | low disease activity | 3 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline | moderate disease activity | 0 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 3 | high disease activity | 1 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Baseline | high disease activity | 8 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 6 | high disease activity | 0 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 3 | remission | 1 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 6 | remission | 3 Participants |
| Group 2 | Change From Baseline in Clinical Disease Activity Index (CDAI) Score | Month 3 | low disease activity | 4 Participants |
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
Time frame: Month 6
Population: Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings | # of patients whose CDAI score improved | 8 participants |
| Group 1 | Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings | # of patients whose overall MRI improved | 6 participants |
| Group 2 | Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings | # of patients whose CDAI score improved | 8 participants |
| Group 2 | Comparison of Clinical Disease Activity Index (CDAI) Scores to Positive Magnetic Resonance Imaging (MRI) Findings | # of patients whose overall MRI improved | 5 participants |
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)
Time frame: Baseline, 3 months, 6 months
Population: Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Evaluation of MRI Structural Improvements | Month 6 : synovitis | 5 participants |
| Group 1 | Evaluation of MRI Structural Improvements | Month 6 : osteitis | 4 participants |
| Group 1 | Evaluation of MRI Structural Improvements | Baseline : synovitis | 8 participants |
| Group 1 | Evaluation of MRI Structural Improvements | Baseline : osteitis | 8 participants |
| Group 1 | Evaluation of MRI Structural Improvements | Baseline : erosions | 9 participants |
| Group 1 | Evaluation of MRI Structural Improvements | Month 3 : synovitis | 6 participants |
| Group 1 | Evaluation of MRI Structural Improvements | Month 3 : osteitis | 6 participants |
| Group 1 | Evaluation of MRI Structural Improvements | Month 3 : erosions | 9 participants |
| Group 1 | Evaluation of MRI Structural Improvements | Month 6 : erosions | 7 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Month 3 : erosions | 8 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Month 6 : erosions | 8 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Baseline : erosions | 8 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Month 6 : osteitis | 4 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Month 3 : osteitis | 6 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Month 6 : synovitis | 7 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Baseline : synovitis | 7 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Month 3 : synovitis | 7 participants |
| Group 2 | Evaluation of MRI Structural Improvements | Baseline : osteitis | 4 participants |
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).
Time frame: Month 3 and Month 6
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1 | Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 3 : Progressed erosions | 1 participants |
| Group 1 | Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 3 : Regressed erosions | 0 participants |
| Group 1 | Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 6 : Progressed erosions | 2 participants |
| Group 1 | Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 6 : Regressed erosions | 1 participants |
| Group 2 | Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 6 : Regressed erosions | 2 participants |
| Group 2 | Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 3 : Progressed erosions | 3 participants |
| Group 2 | Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 6 : Progressed erosions | 2 participants |
| Group 2 | Number of Participants With Increased or Decreased Erosions of the Hand and Wrist | Month 3 : Regressed erosions | 2 participants |
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.
Time frame: Month 6
Population: Total number of Patients who complete 6 months of treatment in both groups doses weekly Group 1, and dosed twice a week Group 2
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1 | Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | CRP Values | # of patient with Decreased values | 8 Participants |
| Group 1 | Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | CRP Values | # of patients with Increased values | 1 Participants |
| Group 1 | Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | ESR Values | # of patient with Decreased values | 9 Participants |
| Group 1 | Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | ESR Values | # of patients with Increased values | 0 Participants |
| Group 2 | Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | ESR Values | # of patients with Increased values | 0 Participants |
| Group 2 | Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | CRP Values | # of patient with Decreased values | 7 Participants |
| Group 2 | Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | ESR Values | # of patient with Decreased values | 8 Participants |
| Group 2 | Participants With Increased and Decreased C-Reactive Protein (CRP) Values and Erythrocyte Sedimentation Rates (ESR) | CRP Values | # of patients with Increased values | 1 Participants |