Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis
Condition: Neuropathy of Sarcoidosis
MeSH terms: Sarcoidosis
Intervention: ARA 290; Placebo
Intervention description: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms.; Formulation buffer
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: neuropathy; sarcoidosis

Summary:

      The purpose of this study is to determine whether ARA 290, a new class of compound, is
      effective in the treatment of the neuropathic symptoms of sarcoidosis. Brief interaction of
      ARA 290 with the innate repair receptor results in anti-apoptotic and anti-inflammatory
      activities in myriad of cells, tissues and organs throughout the body to activate repair
      mechanisms and accelerate healing, including the nerve damage that can be associated with
      sarcoidosis. In this study, subjects with sarcoidosis and symptoms of small fiber neuropathy
      will administered ARA 290 or placebo by subcutaneous injection daily for 28 days. In addition
      to monitoring the safety of the treatment, the symptoms of the subjects will be assessed with
      several questionnaires, function tests, and measurement of nerve fibers in their cornea and
      skin (via a non-invasive test and a biopsy, respectively). The total participation time for
      each patient will be 16 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

        • Established diagnosis of sarcoidosis with both 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 feet

        AND 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 study-related
             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) < 40 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 subject'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, FAS, NPSI)

          -  Refrigerator and freezer at home for storage of study medication.

        Exclusion 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 or could interfere with conduct of
             6-minute walk assessment (as judged by the investigator)

          -  Other medical conditions known to be associated with small nerve fiber loss, except
             for diabetes in good control (as judged by the investigator)

          -  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 of the skin that has been removed

          -  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, other biological anti-inflammatory agents, or immunoglobulins
             administered within the 3 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 subject