Neuropathy of SarcoidosisPhase 2NCT02039687
Study of Efficacy of ARA 290 on Corneal Nerve Fiber Density and Neuropathic Symptoms of Subjects With Sarcoidosis
A Phase 2 study testing ARA 290 in people with Neuropathy of Sarcoidosis, run by Araim Pharmaceuticals, Inc. at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Neuropathy of Sarcoidosis
- What is being tested?
- ARA 290
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jan 2014to Feb 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Established diagnosis of sarcoidosis with both of the following two criteria:
- Score of 4 or greater on Brief Pain Inventory "pain now" or "average pain" questions (BPI; 0 (least discomfort)-10 (worst discomfort))
- 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
- Corneal nerve fiber density reduced compared to normal (i.e., greater than 1 standard deviation less than the mean of a normative population)
- 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)
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
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
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.
Read the 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.
- Conditions
- Neuropathy of Sarcoidosis
- Being tested
- ARA 290, Placebo
- Keywords
- neuropathy, sarcoidosis
- Medical subject headings
- Sarcoidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARA 290Drug
Also called pHSBP, Cibinetide
A small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms.
PlaceboOther
Formulation buffer
| Study group | Role | What they receive |
|---|---|---|
| 1 mg per day ARA 290 | Experimental | 1 mg ARA 290 administered subcutaneously for 28 consecutive days Receives: Drug: ARA 290 |
| 4 mg per day ARA 290 | Experimental | 4 mg ARA 290 administered subcutaneously for 28 consecutive days Receives: Drug: ARA 290 |
| 8 mg per day ARA 290 | Experimental | 8 mg ARA 290 administered subcutaneously for 28 consecutive days Receives: Drug: ARA 290 |
| placebo | Placebo comparator | 1 mL placebo administered subcutaneously for 28 consecutive days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Corneal Nerve Fiber Area
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.
Measured: Baseline and 28 days
Secondary outcomes (4)
Change in the 6 Minute Walk Test
Measurement of the distance a patient can walk in 6 minutes
Measured: Baseline and 28 days
Change in Intra-epidermal Nerve Fiber Density (IENFD)
Measurement of small fiber density in skin biopsies. Density is reduced in sarcoidosis patients, an indication of neuropathy.
Measured: Baseline and 28 days
Change in the Scores of the SFNSL, BPI, NPSI, and FAS Questionnaires
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..
Measured: Baseline to 28 days
Frequency of Adverse Events, Serious Adverse Events, and Laboratory Parameters
Patients reporting at least one treatment emergent adverse event (TEAE) or serious TEAE
Measured: Continuous reporting from baseline through 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionJan 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuropathy of SarcoidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Araim Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Micheal Brines, MD, PhD, Study director, Araim Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02039687
- Sponsor's protocol ID
- APCP-112
- Status last verified
- Mar 2017
- First submitted
- 16 Jan 2014
- Last updated
- 18 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02039687
- Acronym / sponsor ID
- APCP-112
- Conditions
- Neuropathy of Sarcoidosis
- Keywords
- neuropathy, sarcoidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Araim Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Jan 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 20 Jan 2014 (estimated)
- Results
- Posted 18 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 mg per day ARA 290 | Experimental | Drug: ARA 2901 mg ARA 290 administered subcutaneously for 28 consecutive days |
| 4 mg per day ARA 290 | Experimental | Drug: ARA 2904 mg ARA 290 administered subcutaneously for 28 consecutive days |
| 8 mg per day ARA 290 | Experimental | Drug: ARA 2908 mg ARA 290 administered subcutaneously for 28 consecutive days |
| placebo | Placebo comparator | Other: Placebo1 mL placebo administered subcutaneously for 28 consecutive days |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Established diagnosis of sarcoidosis with both of the following two criteria:
- Score of 4 or greater on Brief Pain Inventory "pain now" or "average pain" questions (BPI; 0 (least discomfort)-10 (worst discomfort))
- 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
- Corneal nerve fiber density reduced compared to normal (i.e., greater than 1 standard deviation less than the mean of a normative population)
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARA 290Also: pHSBP, CibinetideA small peptide that activates the innate repair receptor to induce anti-inflammatory and tissue repair mechanisms. | Drug | 1 mg per day ARA 290, 4 mg per day ARA 290, 8 mg per day ARA 290 |
| PlaceboFormulation buffer | Other | placebo |
Primary outcome
Change in Corneal Nerve Fiber Area
Time frame: 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.
4 secondary outcomes
Change in the 6 Minute Walk Test
Time frame: Baseline and 28 days
Change in Intra-epidermal Nerve Fiber Density (IENFD)
Time frame: Baseline and 28 days
Change in the Scores of the SFNSL, BPI, NPSI, and FAS Questionnaires
Time frame: Baseline to 28 days
Frequency of Adverse Events, Serious Adverse Events, and Laboratory Parameters
Time frame: Continuous reporting from baseline through 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Micheal Brines, MD, PhD study director
Araim Pharmaceuticals, Inc.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ARA 290 in people with Neuropathy of Sarcoidosis, run by Araim Pharmaceuticals, Inc. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Corneal Nerve Fiber Area (time frame: Baseline and 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2017; AzTrials last refreshed its copy on 8 Nov 2026.