study the safety and effects of different doses of ARA 290 administered subcutaneously on the corneal nerve fiber density and symptoms of neuropathic pain in sarcoidosis patients.

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2013-003016-45-NL
• Date of registration: 15/08/2013
• Prospective Registration: Yes
• Primary sponsor: Araim Pharmaceuticals
• Public title: study the safety and effects of different doses of ARA 290 administered subcutaneously on the corneal nerve fiber density and symptoms of neuropathic pain in sarcoidosis patients.
• Scientific 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 patients with sarcoidosis - DOSARA
• Date of first enrolment: 11/09/2013
• Target sample size: 64
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003016-45
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Netherlands, United States

Contacts

• Name: Principal Investigator
• Affiliation: Leiden University Medical Center

• Name: Principal Investigator
• Affiliation: Leiden University Medical Center

Key inclusion & exclusion criteria

Inclusion criteria:
Established diagnosis of sarcoidosis with both of the following two criteria:
1) Score of of 4 or greater on Brief Pain Inventory “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)

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, COMPASS-31, NPSI)
Refrigerator and freezer at home for storage of study medication.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64

Exclusion criteria:
Medical history of clinically relevant physical and mental health condition other than conditions related to sarcoidosis, 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 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 that could compromise the safety of the patient
History of severe reaction in the past to Candida or Mumps antigens
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 study personnel
Inability or unwillingness to self-administer ARA 290 via subcutaneous injections (or not have access to home health care for assistance in administration, if needed)
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

small fiber neuropathy

Therapeutic area: Body processes [G] - Biological Phenomena [G16]

Intervention(s)

Product Name: ARA 290
Product Code: ARA 290
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: ARA 290
Current Sponsor code: ARA 290
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 1-8
Pharmaceutical form of the placebo: Powder for solution for injection/infusion
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: Assess changes in small fiber neuropathy score and Brief Pain Inventory

Primary end point(s): change in corneal nerve fiber density

Main Objective: To evaluate the efficacy of different dose levels of ARA 290 administration on different outcome measures of small fiber neuropathy in subjects with sarcoidosis.

Timepoint(s) of evaluation of this end point: at day 28 versus baseline

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Change at day 28 versus baseline
and changes at days 56, 70, 84, 98, and 112 compared to baseline and day 28

Secondary end point(s): Change in IENFD of an ankle biopsy at 28 days versus baseline
Change in the scores of the Small Fiber Neuropathy Screening List, BPI, NPSI, RAND-36, and COMPASS-31 at days 28 and 56 compared to baseline
Change in the 6 minute walk test at day 28 versus baseline
Change in the scores of the Small Fiber Neuropathy Screening List, BPI, NPSI, RAND-36, and COMPASS-31 at days 70, 84, 98 and 112 compared to days 28, 56 and baseline (persistence of effect)
Frequency of adverse events, serious adverse events, and laboratory parameters

Exploratory endpoints:
Change in quantitative sensory testing (QST) at day 28 versus baseline
Change in cardiac autonomic function (heart rate variability; R-R and QT
intervals) at day 28 versus baseline as measured by Cardiac Autonomic
Reflex Testing (CART)

Secondary ID(s)

APCP-112

LUMC protocol number

Source(s) of Monetary Support

Araim Pharmaceuticals