A double blind, placebo controlled Phase 2 dose ranging study of the effects of
ARA 290 on corneal nerve fiber density and neuropathic symptoms of patients
with sarcoidosis.

The subjects will have to present the following criteria:

Established diagnosis of sarcoidosis with any of the following two criteria:

1) Score of 4 or greater on Brief Pain Inventory “pain now” or “average
pain” questions (BPI; 0 (least discomfort)-10 (worst discomfort))

2) Discomfort defined as distal pain/discomfort plus one of the following: 1)
dysesthesia, 2) burning/painful feet worsening at night, or 3) intolerance
of sheets or clothes touching the legs or feetAND either of the following two criteria

1) Corneal nerve fiber density reduced compared to normal (i.e., greater
than 1 standard deviation less than the mean of a normative population)
2) A previous skin biopsy (obtained within the prior 2 years) showing a
reduced intraepidermal nerve fiber density ((i.e., greater than 1 standard
deviation less than the mean of a normal age and gender relevant
population)

In addition, subjects must:

 Be able to read and understand the written consent form, complete studyrelated
procedures, and communicate with the study staff

 Be willing to comply with study restrictions

 Be willing to check in with the study center via the telephone

 Between 18 and 70 years of age (inclusive)

 Body Mass Index (BMI) < 35 kg/m2 (inclusive)

 If female of childbearing potential, a negative urine pregnancy test at
screening and acceptable contraception will be maintained during the
screening and dosing period and 1 month beyond. Acceptable contraception
consists of hormonal methods such as oral, implantable, injectable, or
transdermal contraceptives for a minimum of 1 full cycle (based on the
patient’s usual menstrual cycle period) before study entry, intrauterine device
(IUD), or double-barrier method (condoms, sponge, diaphragm, or vaginal
ring with spermicidal jellies or cream).

 Able to complete self-administered questionnaires (RAND-36, SFNSL, BPI,
COMPASS-31, FAS, NPSI)

 Refrigerator at home for storage of study medication.

The subjects should not present any of the following criteria:

 Clinically relevant abnormal history of physical and mental health other than
conditions related to sarcoidosis, as determined by medical history taking (as
judged by the investigator)

 Clinically relevant abnormal laboratory results, vital signs, or physical findings
other than conditions related to sarcoidosis (as judged by the investigator) or
could interfere with conduct of 6-minute walk assessment

 Known clinically relevant abnormalities in ECG (as judged by the
investigator)

 Illicit drug abuse or excessive alcohol consumption (as judged by the
investigator)

 History of serious malignancy within the last 5 years other than a basal cell or
squamous cell carcinoma that has been removed

 History of fainting (as judged by the investigator)

 History of severe allergies, or has had an anaphylactic reaction or significant
intolerability to prescription or non-prescription drugs or food (as judged by
the investigator)

 Anti-TNF therapy or other biological anti-inflammatory agents administered
within the 6 months prior to screening.

 Use of erythropoiesis stimulating agents within the two months prior to
screening or during the trial

 Participation in an investigational drug trial in the 3 months prior to
administration of the initial dose of study drug or more than 4 times in the
calendar year preceding study enrollment

 Inadequate venous accessibility as judged by clinicians (physician or nurse)

 Inability or unwillingness to self-administer ARA 290 via subcutaneous
injections (or not have access to home health care for assistance in
administration)

 If female, pregnant or breast-feeding

 Any other condition that in the opinion of the investigator would complicate or
compromise the study, or the well-being of the patient