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Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis

Sponsor
Araim Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02039687
Collaborator
(none)
64
Enrollment
2
Locations
4
Arms
13
Duration (Months)
32
Patients Per Site
2.5
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: ARA 290
  • Other: Placebo
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
64 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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 Subjects With Sarcoidosis
Study Start Date :
Jan 1, 2014
Actual Primary Completion Date :
Jan 1, 2015
Actual Study Completion Date :
Feb 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1 mg per day ARA 290

1 mg ARA 290 administered subcutaneously for 28 consecutive days

Drug: ARA 290
A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms.
Other Names:
  • pHSBP, Cibinetide

    		•
    Experimental: 4 mg per day ARA 290

    4 mg ARA 290 administered subcutaneously for 28 consecutive days

    Drug: ARA 290
    A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms.
    Other Names:
  • pHSBP, Cibinetide

    		•
    Experimental: 8 mg per day ARA 290

    8 mg ARA 290 administered subcutaneously for 28 consecutive days

    Drug: ARA 290
    A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms.
    Other Names:
  • pHSBP, Cibinetide

    		•
    Placebo Comparator: placebo

    1 mL placebo administered subcutaneously for 28 consecutive days

    Other: Placebo
    Formulation buffer

    Outcome Measures

    Primary Outcome Measures

    1. Change in Corneal Nerve Fiber Area [Baseline and 28 days]

      Measurement of corneal nerve fiber area is a non-invasive procedure performed at baseline and at the end of dosing and at 12 weeks follow-up. The nerve fiber area in sarcoidosis patients is reduced compared to normal humans, a measurement of small fiber loss.

    Secondary Outcome Measures

    1. Change in the 6 Minute Walk Test [Baseline and 28 days]

      Measurement of the distance a patient can walk in 6 minutes

    2. Change in Intra-epidermal Nerve Fiber Density (IENFD) [Baseline and 28 days]

      Measurement of small fiber density in skin biopsies. Density is reduced in sarcoidosis patients, an indication of neuropathy.

    3. Change in the Scores of the SFNSL, BPI, NPSI, and FAS Questionnaires [Baseline to 28 days]

      Change in mean score from baseline to Day 28 is recorded for each outcome. Brief Pain Inventory (BPI), Pain Severity - scale of 0 (no pain) to 10 (worst pain imaginable) in 4 time frames, averaged. BPI, Pain Interference - scale of 0 (does not interfere) to 10 (completely interferes) how pain interferes with 7 lifestyle parameters, averaged. Small Fiber Neuropathy Screening List (SFNSL) - scale of 0 to 84 (higher score indicates greater neuropathy), sum of 21 questions. Neuropathic Pain Symptom Inventory (NPSI) - scale of 0 (least pain) to 10 (most pain) in 10 questions, summed. Total score range from 0 to 100. Fatigue Assessment Scale (FAS) - scale of 1 (never) to 5 (always) in 10 questions related to fatigue, summed. Total score range from 0 to 50, with 0 being the best possible score and 50 the worst..

    4. Frequency of Adverse Events, Serious Adverse Events, and Laboratory Parameters [Continuous reporting from baseline through 16 weeks]

      Patients reporting at least one treatment emergent adverse event (TEAE) or serious TEAE

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cleveland Clinic Cleveland Ohio United States 44195
    2 Leiden University Medical Center Leiden Netherlands

    Sponsors and Collaborators

    • Araim Pharmaceuticals, Inc.

    Investigators

    • Study Director: Micheal Brines, MD, PhD, Araim Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Araim Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02039687
    Other Study ID Numbers:
    • APCP-112
    First Posted:
    Jan 20, 2014
    Last Update Posted:
    Apr 18, 2017
    Last Verified:
    Mar 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Araim Pharmaceuticals, Inc.
    neuropathy
    sarcoidosis
    Additional relevant MeSH terms:
    Sarcoidosis

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title 1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Arm/Group Description 1 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 4 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 8 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 1 mL placebo administered subcutaneously for 28 consecutive days Placebo: Formulation buffer
    Period Title: Overall Study
    STARTED 16 16 16 16
    COMPLETED 16 15 13 16
    NOT COMPLETED 0 1 3 0

    Baseline Characteristics

    Arm/Group Title 1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo Total
    Arm/Group Description 1 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 4 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 8 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 1 mL placebo administered subcutaneously for 28 consecutive days Placebo: Formulation buffer Total of all reporting groups
    Overall Participants 16 16 14 16 62
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    51.4
    (7.47)
    51.8
    (10.75)
    52.2
    (9.17)
    47.8
    (10.66)
    50.8
    (9.55)
    Sex: Female, Male (Count of Participants)
    Female
    8
    50%
    9
    56.3%
    6
    42.9%
    9
    56.3%
    32
    51.6%
    Male
    8
    50%
    7
    43.8%
    8
    57.1%
    7
    43.8%
    30
    48.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    6.3%
    0
    0%
    0
    0%
    1
    1.6%
    White
    16
    100%
    15
    93.8%
    14
    100%
    16
    100%
    61
    98.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Change in Corneal Nerve Fiber Area
    Description Measurement of corneal nerve fiber area is a non-invasive procedure performed at baseline and at the end of dosing and at 12 weeks follow-up. The nerve fiber area in sarcoidosis patients is reduced compared to normal humans, a measurement of small fiber loss.
    Time Frame Baseline and 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Arm/Group Description 1 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 4 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 8 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 1 mL placebo administered subcutaneously for 28 consecutive days Placebo: Formulation buffer
    Measure Participants 16 16 14 16
    Mean (Standard Deviation) [µm^2]
    -64.3
    (759.9)
    533.8
    (1110.02)
    203.8
    (641.2)
    -170.0
    (633.0)
    2. Secondary Outcome
    Title Change in the 6 Minute Walk Test
    Description Measurement of the distance a patient can walk in 6 minutes
    Time Frame Baseline and 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Arm/Group Description 1 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 4 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 8 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 1 mL placebo administered subcutaneously for 28 consecutive days Placebo: Formulation buffer
    Measure Participants 16 16 14 16
    Mean (Standard Deviation) [meters]
    19.3
    (79.27)
    17.7
    (40.29)
    18.2
    (47.9)
    1.2
    (38.56)
    3. Secondary Outcome
    Title Change in Intra-epidermal Nerve Fiber Density (IENFD)
    Description Measurement of small fiber density in skin biopsies. Density is reduced in sarcoidosis patients, an indication of neuropathy.
    Time Frame Baseline and 28 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Arm/Group Description 1 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 4 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 8 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 1 mL placebo administered subcutaneously for 28 consecutive days Placebo: Formulation buffer
    Measure Participants 16 16 14 16
    Mean (Standard Deviation) [fibers/mm]
    0.5
    (1.58)
    0.4
    (2.28)
    -0.3
    (1.81)
    0.8
    (1.13)
    4. Secondary Outcome
    Title Change in the Scores of the SFNSL, BPI, NPSI, and FAS Questionnaires
    Description Change in mean score from baseline to Day 28 is recorded for each outcome. Brief Pain Inventory (BPI), Pain Severity - scale of 0 (no pain) to 10 (worst pain imaginable) in 4 time frames, averaged. BPI, Pain Interference - scale of 0 (does not interfere) to 10 (completely interferes) how pain interferes with 7 lifestyle parameters, averaged. Small Fiber Neuropathy Screening List (SFNSL) - scale of 0 to 84 (higher score indicates greater neuropathy), sum of 21 questions. Neuropathic Pain Symptom Inventory (NPSI) - scale of 0 (least pain) to 10 (most pain) in 10 questions, summed. Total score range from 0 to 100. Fatigue Assessment Scale (FAS) - scale of 1 (never) to 5 (always) in 10 questions related to fatigue, summed. Total score range from 0 to 50, with 0 being the best possible score and 50 the worst..
    Time Frame Baseline to 28 days

    Outcome Measure Data

    Analysis Population Description
    Questionnaires incomplete for some subjects
    Arm/Group Title 1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Arm/Group Description 1 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 4 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 8 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 1 mL placebo administered subcutaneously for 28 consecutive days Placebo: Formulation buffer
    Measure Participants 16 16 14 16
    BPI - Pain Severity
    -0.594
    (1.6680)
    -1.167
    (1.6894)
    -1.115
    (1.7067)
    -0.922
    (1.4429)
    BPI - Pain Interference
    -1.187
    (1.9453)
    -1.657
    (1.6482)
    -1.308
    (2.4403)
    -1.732
    (2.2174)
    SFNSL
    -4.9
    (8.87)
    -8.7
    (14.17)
    -5.5
    (7.09)
    -7.3
    (9.50)
    NPSI
    -12.31
    (16.074)
    -14.50
    (17.887)
    -8.38
    (12.699)
    -12.88
    (13.803)
    FAS
    -2.6
    (5.52)
    -2.1
    (5.38)
    -3.1
    (5.27)
    -2.2
    (6.00)
    5. Secondary Outcome
    Title Frequency of Adverse Events, Serious Adverse Events, and Laboratory Parameters
    Description Patients reporting at least one treatment emergent adverse event (TEAE) or serious TEAE
    Time Frame Continuous reporting from baseline through 16 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Arm/Group Description 1 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 4 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 8 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 1 mL placebo administered subcutaneously for 28 consecutive days Placebo: Formulation buffer
    Measure Participants 16 16 14 16
    Patients reporting at least one TEAE
    14
    87.5%
    11
    68.8%
    12
    85.7%
    12
    75%
    Patients reporting at least one serious TEAE
    2
    12.5%
    0
    0%
    1
    7.1%
    0
    0%

    Adverse Events

    Time Frame 28 day treatment with 84 day follow up
    Adverse Event Reporting Description
    Arm/Group Title 1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Arm/Group Description 1 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 4 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 8 mg ARA 290 administered subcutaneously for 28 consecutive days ARA 290: A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. 1 mL placebo administered subcutaneously for 28 consecutive days Placebo: Formulation buffer
    All Cause Mortality
    1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/16 (12.5%) 0/16 (0%) 1/14 (7.1%) 0/16 (0%)
    Gastrointestinal disorders
    Small Bowel Enteritis 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    General disorders
    Chest Tightness 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Nervous system disorders
    Syncope 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Headache 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Psychiatric disorders
    Suicidal Ideation 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Shortness of Breath 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Other (Not Including Serious) Adverse Events
    1 mg Per Day ARA 290 4 mg Per Day ARA 290 8 mg Per Day ARA 290 Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/16 (87.5%) 11/16 (68.8%) 12/14 (85.7%) 12/16 (75%)
    Cardiac disorders
    Palpitations 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Ear and labyrinth disorders
    Vertigo 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Eye disorders
    Vision blurred 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 1/16 (6.3%) 1
    Accommodation disorder 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Blepharitis 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Conjunctival haemorrhage 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Eye irritation 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Eyelid oedema 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Gastrointestinal disorders
    Diarrhoea 2/16 (12.5%) 2 1/16 (6.3%) 1 2/14 (14.3%) 2 2/16 (12.5%) 2
    Nausea 2/16 (12.5%) 2 2/16 (12.5%) 2 1/14 (7.1%) 1 0/16 (0%) 0
    Abdominal Pain 1/16 (6.3%) 1 1/16 (6.3%) 1 0/14 (0%) 0 1/16 (6.3%) 1
    Abnormal faeces 0/16 (0%) 0 1/16 (6.3%) 1 1/14 (7.1%) 1 0/16 (0%) 0
    Dyspepsia 2/16 (12.5%) 2 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Constipation 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Crohn's disease 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Dry mouth 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Eructation 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Gastrointestinal pain 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Salivary gland enlargement 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Toothache 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    General disorders
    Fatigue 3/16 (18.8%) 4 2/16 (12.5%) 2 0/14 (0%) 0 2/16 (12.5%) 2
    Injection site pain 1/16 (6.3%) 1 1/16 (6.3%) 1 1/14 (7.1%) 1 4/16 (25%) 4
    Feeling abnormal 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 1/16 (6.3%) 1
    Asthenia 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Disease progression 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Impaired healing 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Influenza like illness 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Injection site discomfort 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Injection site haemorrhage 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Injection site irritation 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Oedema peripheral 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Temperature intolerance 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Immune system disorders
    Allergy to arthropod sting 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Hypersensitivity 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 2 0/16 (0%) 0
    Infections and infestations
    Nasopharyngitis 0/16 (0%) 0 3/16 (18.8%) 3 0/14 (0%) 0 2/16 (12.5%) 2
    Urinary tract infection 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 1/16 (6.3%) 1
    Acute sinusitis 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Atypical pneumonia 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Bacterial vaginosis 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Bronchitis 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Cellulitis 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Gastroenteritis 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Mastoiditis 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Meningitis aseptic 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Oral herpes 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Orchitis 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Respiratory tract infection viral 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Sinusitis 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Streptococcal infection 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Tooth infection 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Upper respiratory tract infection 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Viral infection 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Injury, poisoning and procedural complications
    Wound 1/16 (6.3%) 1 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Animal bite 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Epicondylitis 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Fibula fracture 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Injection related reaction 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Meniscus injury 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Muscle strain 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Post procedural haematoma 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Procedural pain 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Investigations
    Oxygen saturation decreased 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 2
    Metabolism and nutrition disorders
    Folate deficiency 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Musculoskeletal and connective tissue disorders
    Muscle spasms 0/16 (0%) 0 1/16 (6.3%) 1 1/14 (7.1%) 1 2/16 (12.5%) 2
    Pain in extremity 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 2/16 (12.5%) 2
    Arthralgia 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Back pain 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Flank pain 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Joint stiffness 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Joint swelling 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Musculoskeletal pain 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Musculoskeletal stiffness 1/16 (6.3%) 2 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Neck pain 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Tendonitis 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Nervous system disorders
    Headache 3/16 (18.8%) 3 3/16 (18.8%) 3 2/14 (14.3%) 2 0/16 (0%) 0
    Muscle contractions involuntary 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 1/16 (6.3%) 1
    Paraesthesia 1/16 (6.3%) 1 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Somnolence 1/16 (6.3%) 1 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Tremor 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 1/16 (6.3%) 1
    Burning sensation 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Dizziness exertional 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Hypoaesthesia 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Mental Impairment 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Presyncope 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Retrograde Amnesia 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Tension headache 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Psychiatric disorders
    Insomnia 2/16 (12.5%) 3 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Abnormal dreams 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Agitation 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Burnout syndrome 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Depressed mood 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Tearfulness 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Renal and urinary disorders
    Dysuria 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Haematuria 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Renal failure 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/16 (6.3%) 1 0/16 (0%) 0 1/14 (7.1%) 1 1/16 (6.3%) 1
    Asthma 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 1/16 (6.3%) 1
    Nasal congestion 1/16 (6.3%) 1 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Epitaxis 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Painful respiration 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0
    Skin and subcutaneous tissue disorders
    Hyperhidrosis 1/16 (6.3%) 1 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Pruritis 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Rash macular 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Rosacea 0/16 (0%) 0 1/16 (6.3%) 1 0/14 (0%) 0 0/16 (0%) 0
    Sticky skin 1/16 (6.3%) 1 0/16 (0%) 0 0/14 (0%) 0 0/16 (0%) 0
    Vascular disorders
    Hypertension 0/16 (0%) 0 0/16 (0%) 0 0/14 (0%) 0 1/16 (6.3%) 1
    Hypotension 0/16 (0%) 0 0/16 (0%) 0 1/14 (7.1%) 1 0/16 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Araim Pharmaceuticals, Inc.
    Phone 914-762-7586
    Email info@araimpharma.com
    Responsible Party:
    Araim Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT02039687
    Other Study ID Numbers:
    • APCP-112
    First Posted:
    Jan 20, 2014
    Last Update Posted:
    Apr 18, 2017
    Last Verified:
    Mar 1, 2017