Phase 1 Trial of Type II Collagen (CII) APL A12 in Rheumatoid Arthritis Patients
Rheumatoid Arthritis
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis
Eligibility Criteria
Inclusion Criteria:
Patients must meet the following criteria for participation in the study.
- Male or female; age > 18 years.
- American College of Rheumatology (ACR) 1988 revised criteria for rheumatoid arthritis.
- Onset of disease age 16 or older.
- Onset of disease at least 3 months prior to enrollment.
- RA patients ages 18-85 with RA of 3 month duration which in the opinion of the examining rheumatologist is "clinically stable" and will likely not require adjustment of doses of Disease-modifying antirheumatic drugs (DMARDS), NSAIDS, prednisone, anti-tumor necrosis factor (anti-TNF) alpha therapies for the 16 weeks of the treatment phase of the study.
- Patients must agree to discontinue all "herbal remedies" as described in this protocol.
- Women of childbearing age will be advised to use effective means of contraception for the treatment phase of the trial and for 90 days thereafter. They must have a negative urine pregnancy test at the randomization visit. (Required by the FDA.)
- Men will be advised to use effective means of contraception for the treatment phase of the trial and for 90 days thereafter. (Required by the FDA.)
- Crohn's Disease Activity Index (CDAI) less than or equal to 30 at the baseline visit.
- Patients with a past history of malignant neoplasm will be eligible if they are 1 or greater years with no recurrence of malignant neoplasm.
Exclusion Criteria:
- Inability to render an informed consent in accordance with institutional guidelines.
- Participation in another clinical research study involving the evaluation of another investigational drug within 90 days of entry into this study.
- RA patients on >7.5 mg prednisone a day.
- RA patients with intra-articular corticosteroid injections during the previous 30 days.
- Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for the study. Hepatitis B abd/or C patients with inactive disease (as determined by PI) will be enrolled.
- Positive urine pregnancy test
- Age 85 years or greater.
- Use of "fish oil" within the previous 4 weeks of the baseline visit.
- Therapy consisting of auranofin or cyclophosphamide (all other DMARDs are allowed).
- Previous autologous or heterologous stem cell transplantation.
- Active malignant neoplasm or past treatment for malignant neoplasm 1 year from screening visit.
- Use of oral CII within the past 1 year. (Since oral tolerance is short-lived, we will permit patients in the study who have been off oral CII for > 1 year)
- Diabetes requiring insulin or on oral medications must be well managed at baseline. Adjustment of insulin or on oral medications will be allowed during the study.
- Serum creatinine 2.0 mcg/dL.
- An 1(II) IFN value <100% of the PBS IFN value within 1 month or less prior to the baseline and less than 25% reduction in APL A12 + 1(II) IFN from 1(II) IFN concentration.
- CDAI > 30 at the baseline visit.
Sites / Locations
- Memphis VA Medical Center, Memphis, TN
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Arm 1
Arm 2
Arm 3
The study will have 3 treatment arms each with 10-12 patients who have demonstrated T cell immunity to CII and have an in vitro response to APL A12 at the screening visit. Patients will be randomized to one of the 2 treatment arms (30 micrograms APL A12 or placebo). Each of the 2 treatments will be given for 16 weeks. Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate. Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate.
The next group will receive a higher dose (50 micrograms) and/or placebo (Block 2). Intervention: Drug treatment will be stopped or interrupted if indicated and medical care will be given as appropriate.
Block 3 (Arm 3) will include placebo and both doses of APL/A12 to ensure 10-12 patients are enrolled in each arm ( total of approximately 32 subjects) so we will have 24 subjects who complete the 16 weeks of study treatment. Arms 2 and 3 will run simultaneously. Intervention: Drug treatment will be stopped or interrupted if indicated.