ACTHAR for Acute Treatment of Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate

The standard treatment for rheumatoid arthritis is using disease-modifying anti-rheumatic
drugs such as methotrexate to control joint pain and swelling. Often times rheumatoid
arthritis patients experience inadequate response to methotrexate with acute or persistent
joint pain and swelling. In these patients, alternative or additional immunosuppressive
therapy is needed to induce disease remission. In the present clinical trial, ACTHAR is
being studied to induce disease remission on rheumatoid arthritis patients who have
inadequate response to methotrexate therapy.

Inclusion Criteria:

- Male or female at least 18 years of age at the time of screening

- Subject is diagnosed with RA no less than 6 months prior to the screening

- Subject meets the 2010 ACR/EULAR Classification Criteria for RA (Arthritis Rheum
2010:62;2569-2581) with a score of ≥6

- Subject is seropositive for RF and/or anti-CCP antibodies as part of the diagnostic
criteria for RA

- Subject has moderately to severely active RA during screening, as defined by a
DAS28-ESR > 3.2

- Subject has moderately to severely active RA defined as the presence of at least 6/68
tender joints and at least 6/66 swollen joints

- Subject has had an inadequate response to the continuous use of methotrexate for at
least 12 weeks prior to study entry with a nonchanging dose for at least 8 weeks
prior to study entry

Exclusion Criteria:

- Treatment with any investigational agent within 4 weeks (or 5 half-lives of the
investigational drug, whichever is longer) of screening

- Treatment with any biological agents within 4 weeks (or 5 half-lives of the agent,
whichever is longer) of screening

- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline

- Evidence of serious uncontrolled concomitant cardiovascular, nervous system,
pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine
(including Cushing's disease or uncontrolled diabetes mellitus) or gastrointestinal
disease (including complicated diverticulitis, ulcerative colitis, or Crohn's
disease.)

- Current liver disease as determined by principal investigator unless related to
primary disease under investigation

- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
or other infections (including but not limited to tuberculosis and atypical
mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal
infections of nail beds)

- Any major episode of infection requiring hospitalization or treatment with IV
antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
screening

- Active TB requiring treatment within the previous 3 years. Patients should be
screened for latent TB and, if positive, treated following local practice guidelines
prior to initiating treatment. Patients treated for tuberculosis with no recurrence
in 3 years are permitted.

- Evidence of active malignant disease, malignancies diagnosed within the previous 10
years (including hematological malignancies and solid tumors, except basal and
squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has
been excised and cured), or breast cancer diagnosed within the previous 20 years
unless related to primary disease under investigation

- Pregnant women or nursing (breast feeding) mothers

- Patients with reproductive potential not willing to use an effective method of
contraception.

- History of alcohol, drug or chemical abuse within 1 year prior to screening.

- Neuropathies or other conditions that might interfere with pain evaluation unless
related to primary disease under investigation.

- Body weight of > 150 kg

- Serum creatinine > 1.6 mg/dL (141 µmol/L) in female subjects and > 1.9 mg/dL (168
µmol/L) in male subjects. Subjects with serum creatinine values exceeding limits may
be eligible for the study if their estimated glomerular filtration rates (GFR) are
>30

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper
limit of normal (ULN)

- Total Bilirubin > ULN

- Platelet count < 100 x 109/L (100,000/mm3)

- Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)

- White Blood Cells < 3.0 x 109/L (3000/mm3)

- Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)

- Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)

- Positive Hepatitis BsAg or Hepatitis C antibody

- Major surgery (including joint surgery) within 8 weeks prior to screening or planned
major surgery within 6 months following randomization

- A diagnosis of any of the followings: scleroderma, osteoporosis, infection throughout
the body, ocular herpes simplex, history of or a current stomach ulcer, uncontrolled
hypertension (systolic blood pressure greater than 160), or allergy to pig‐derived
proteins

- Subject does not tolerate methotrexate and/or NSAID due to side effects or toxicities