6-Month Phase I/II Open Label PRTX-100 in Previous Rheumatoid Arthritis Study Participants and Sera Collection

Although the majority of RA patients achieve an amelioration of their RA with older disease
modifying agents such as methotrexate and leflunomide, all of these agents provoke adverse
events. The newer more active biological agents have a distinct safety profile that includes
an increased risk of serious infections. They have an annual treatment expense in the tens of
thousands of dollars a year. PRTX-100 may be able to modify the disease course of rheumatoid
arthritis with an improved safety profile compared to available agents and a dosing regimen
comparable to the therapies currently available. This study is done to describe the adverse
event profile of 6 μg/kg of PRTX-100 administered IV for longer periods of treatment that
might be required for RA therapy. Secondary objectives include: evaluation of the clinical
response of subjects with previous administration of PRTX-100; evaluation of anti-PRTX
antibody presence and effect on activity; evaluation of "Power Doppler" ultrasound in the
assessment of joint inflammation; and evaluation of biomarkers.

Assay development is an intrinsic part of drug and biological development. The current assay
for anti-PRTX-100 antibodies depends on a very limited supply of serum available from
individuals in early trials. It will be necessary to obtain adequate antisera to provide
immunological reagents for this assay. It is not known whether the character of anti-PRTX-100
antibodies from volunteers is similar to those produced by patients with immunological
disorders on cytotoxic therapy. Antisera will be developed in normal volunteers. The
anti-PRTX-100 antibody assay will need to be standardized with a new anti-PRTX-100 antibody
source compared to the present human reagent.

Part A Inclusion Criteria:

1. Has completed the written informed consent process

2. Received PRTX-100 or placebo in Study 104

3. Receiving methotrexate or leflunomide therapy for at least 12 weeks

4. Must be on a stable weekly dose of methotrexate (12.5 to 25 mg) or daily leflunomide
(10-20 mg/day) by the same route of administration for at least 3 weeks prior to the
start of study drug.

5. Agrees to notify the investigator when deviating from protocol requirements for
concomitant medications

6. Agrees to stay in contact with the study site for the duration of the study, provide
updated contact information as necessary, and has no current plans to move from the
study area for the duration of the study

7. Agrees to avoid elective surgery for the full duration of the study

8. For female subjects: agrees to avoid pregnancy from 28 days prior to Study Day 0 and
for the full duration of the study. Women physically capable of pregnancy (not
sterilized and still menstruating or within 1 year of the last menses if menopausal)
in sexual relationships with men must use an acceptable method of avoiding pregnancy
during this period. Acceptable methods of avoiding pregnancy include a sterile sexual
partner, sexual abstinence (not engaging in sexual intercourse), hormonal
contraceptives (oral, injection, transdermal patch, or implant), vaginal ring,
intrauterine device (IUD), or the combination of a condom or diaphragm with
spermicide.

Part A Exclusion Criteria:

1. Diagnosis of any other inflammatory arthritis (e.g. psoriatic arthritis,
spondyloarthropathy, gout)

2. ACR Functional Classification IV

3. Systemic involvement secondary to rheumatoid arthritis (vasculitis, pulmonary fibrosis
or Felty's syndrome. Secondary Sjogren's syndrome is permitted.

4. Any receipt of abatacept, adalimumab, certolizumab pegol, etanercept, golimumab,
tocilizumab or tofacitinib within 3 weeks of Study Day 0

5. Any receipt of infliximab within 6 weeks of Study Day 0

6. Any receipt of rituximab or other anti-CD20 antibodies within 12 months of study day 0

7. Any receipt of another investigational product within 4 weeks or 4 half-lives
whichever is longer prior to Study Day 0

8. Hepatitis B surface antigen positive, HIV positive, hepatitis C antibody positive

9. Uncontrolled Type 2 Diabetes or Type I diabetes

10. Positive urine pregnancy test

11. Diagnosis of hepatic cirrhosis

12. Urinalysis must reflect no evidence of systemic or local disease process

13. Severe anemia, defined as < 10 g/dL or hematocrit < 30%

14. Evidence of significant active infection

15. Shared a residence within the last year with an individual on anti-tuberculosis
treatment or with culture or smear positive tuberculosis

16. Previous medical history that may compromise the safety of the subject in the study,
including but not limited to: severe impairment of pulmonary function or other
pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected
progressive neurological disease or poorly controlled epilepsy

17. Evidence of a new acute illness that may compromise the safety of the subject in the
study

18. History or evidence on physical examination of any systemic disease or any acute or
chronic illness that, in the opinion of the investigator, may interfere with the
evaluation of the safety of the study drug

19. History or evidence (including chest X-ray) of active tuberculosis

20. Any current medical, psychiatric, occupational, or substance abuse problems that, in
the opinion of the investigator, will make it unlikely that the subject will comply
with the protocol.

Part B Inclusion Criteria

1. Has completed the written informed consent process

2. Is in a state of good health

3. Agrees to stay in contact with the study site for the duration of the study, provide
updated contact information as necessary, and has no current plans to move from the
study area for the duration of the study

4. Agrees to avoid elective surgery for the full duration of the study

5. For female subjects: agrees to avoid pregnancy from 28 days prior to Study Day 0 and
for the full duration of the study. Women physically capable of pregnancy (not
sterilized and still menstruating or within 1 year of the last menses if menopausal)
in sexual relationships with men must use an acceptable method of avoiding pregnancy
during this period. Acceptable methods of avoiding pregnancy include a sterile sexual
partner, sexual abstinence (not engaging in sexual intercourse), hormonal
contraceptives (oral, injection, transdermal patch, or implant), vaginal ring,
intrauterine device (IUD), or the combination of a condom or diaphragm with
spermicide.

Part B Exclusion Criteria

1. Diagnosis of cancer or autoimmune disease.

2. Any receipt of another investigational product within 4 weeks or 4 half-lives
whichever is longer prior to Study Day 0

3. Hepatitis B surface antigen positive, HIV positive, hepatitis C antibody positive

4. Uncontrolled Type 2 Diabetes or Type I diabetes

5. Diagnosis of hepatic cirrhosis

6. Positive urine pregnancy test

7. Urinalysis must reflect no evidence of systemic or local disease process

8. Severe anemia, defined as < 10 g/dL or hematocrit < 30%

9. Previous medical history that may compromise the safety of the subject in the study,
including but not limited to: severe impairment of pulmonary function or other
pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected
progressive neurological disease or poorly controlled epilepsy

10. Evidence of a new acute illness that may compromise the safety of the subject in the
study

11. History or evidence on physical examination of any systemic disease or any acute or
chronic illness that, in the opinion of the investigator, may interfere with the
evaluation of the safety of the study drug

12. Any current medical, psychiatric, occupational, or substance abuse problems that, in
the opinion of the investigator, will make it unlikely that the subject will comply
with the protocol.