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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      This was a double-blind, randomized, placebo-controlled study to assess the effects of daily
      SC administration of ARA 290 at a dose of 1 mg, 4 mg, or 8 mg or placebo on corneal nerve
      fiber density of subjects with sarcoidosis and neuropathic symptoms consistent with small
      fiber neuropathy. The safety of these doses was also assessed.

      Up to 64 subjects with sarcoidosis and symptoms of small fiber neuropathy were planned to be
      enrolled in the study. Subjects determined to be eligible at the screening visit were asked
      to return to the study site for the start of the treatment period (Visit 1, study day 1)
      within 28 days of screening. Subjects who were not able to return for Visit 1 within 28 days
      of the screening visit could be rescreened. At Visit 1, the subjects were randomized to one
      of 4 treatment groups (approximately 16 subjects per group): 1 mg, 4 mg, or 8 mg of ARA 290
      or placebo. The study drug (ARA 290 or placebo) was to be administered daily for 28 days via
      SC injection. The first injection of study drug was administered at the study site at Visit
      1. After the first injection, the subjects were required to stay at the research site for 1
      hour post dose for safety observation and recording of any adverse events (AEs). The subjects
      were trained for self-injection of the study drug and asked to self-administer the study
      medication daily at home before breakfast for the remaining treatment period using the
      supplied individual vials and disposable insulin needles and syringes.

      The subjects were asked to visit the study site after 14 ± 2 days of dosing (Visit 2) and at
      the end of the treatment period Day 28 ± 2 (Visit 3). Additionally, the study personnel
      contacted the subjects by telephone at study days 7 and 21. Following the treatment period
      the subjects were followed-up for a further 12 weeks (until study day 112). During this
      period the subjects visited the study site at Day 56 ± 2 days (Visit 4) and study personnel
      contacted the subjects by telephone at study days 35 and 42 and biweekly from study days 70
      to 112. The duration of study participation for each subject was 16 weeks. Throughout the
      study the subjects were asked to complete several questionnaires regarding general health and
      well-being, pain, fatigue and neuropathic symptoms. Further assessments included the 6MWT,
      and determination of nerve fiber density. If feasible at the site, quantitative sensory and
      cardiac autonomic reflex testing were to be performed.

      The protocol was later amended to administer the Columbia-Suicide Severity Rating Scale
      (C-SSRS). Any positive results for active suicidal ideation and behavior, based on evaluation
      of the C-SSRS questionnaire, were reported as AEs. During the treatment period the subjects
      were also asked to complete a diary card to document compliance. Safety assessments included
      the documentation of AEs, vital signs and electrocardiogram (ECG), safety laboratory,
      physical examination and a test for ARA 290 antibodies.
    

Intervention name(s): ARA 290; Placebo
Intervention type(s): Drug; Other
Intervention description(s): A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms.; Formulation buffer
Other intervention name(s): pHSBP, Cibinetide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: neuropathy; sarcoidosis