Proof of Concept of VLY-686 in Subjects With Treatment-Resistant Pruritus Associated With Atopic Dermatitis

This is an interventional treatment trial for Treatment-resistant Pruritus Associated With Atopic Dermatitis focused on measuring pruritus, atopic dermatitis, VLY-686 Read More

Inclusion Criteria:

• Men and women ages 18 - 65 years, inclusive; suffering from atopic dermatitis with a SCORAD index at inclusion ≤80;
• With atopic lesions on arms, legs, trunk and neck;
• Chronic pruritus with pruritus being actively present for at least 6 weeks prior to screening;
• Subjects who have treatment-resistant pruritus; pruritus duration of > 6 weeks despite the use of antihistamines or corticosteroids;
• Pruritus VAS intensity ≥70 mm (mean intensity during one of the two days preceding inclusion into the study / Baseline Visit)and patient assessment of pruritus (PGA Likert scale item "pruritus") at inclusion ≥3;
• Subjects with Body Mass Index (BMI) of ≥18 and ≤35 kg/m2 (BMI = weight (kg)/ [height (m)]2);
• Males, non-fecund females, or females of child-bearing potential using 2 independent highly effective barrier methods of birth control when used correctly for a period of 35 days before the first dosing, during the study and for one month after the last dose and must have a negative pregnancy test at the screening and baseline visits;
• Vital signs (after 3 minutes resting in a sitting or semi-supine position) which are within the following ranges: Body temperature between 35.5-37.8 °C, -Systolic blood pressure between 91-130 mmHg, Diastolic blood pressure between 51-90 mmHg, Pulse rate between 50-100 bpm;
• Ability and acceptance to provide written informed consent;
• Willing and able to comply with study requirements and restrictions including the discontinuation of all current therapies for pruritus;
• Willing to not participate in any other clinical trials for the duration of the VLY-686 trial;
• Subjects must be in good health as determined by past medical history, physical examination, electrocardiogram, clinical laboratory tests and urinalysis.

Exclusion Criteria:

• Chronic pruritus due to conditions other than atopic dermatitis (AD) including the following conditions: Prurigo nodularis, Lichen simplex chronicus, Bullous pemphigoid;
• Other non-AD subjects (notalgia paresthetica, brachioradial pruritus, somatoform prurigo, dilusional parasitosis, depression associated prurigo);
• Acute superinfection of AD;
• Current and past systematic use of topical or systemic antihistamines (2 weeks prior to the Baseline Visit, topical steroids (2 weeks prior to the Baseline Visit), systemic steroids (6 weeks prior to the Baseline Visit), cytotoxic treatment (4 weeks prior to the Baseline Visit), cyclosporin A and other immunosuppressants (8 weeks prior to the Baseline Visit), naltrexone, paroxetine, fluvoxamine, amitriptyline, gabapentin, pregabalin (prescribed for the pruritus treatment, 4 weeks prior to the Baseline Visit), topical calcineurin inhibitors, topical antibiotics, antiseptic bathes and cleansing lotions (8 weeks prior to the Baseline Visit);
• Under actual medical treatment for a skin disease with a therapy listed in the prohibited medications section that may influence the results of the study;
• History of recent (within six months) drug or alcohol abuse as defined in DSM V, Diagnostic Criteria for Drug and Alcohol Abuse or evidence of such abuse as indicated by the laboratory assays conducted during the Screening or Baseline Visits;
• Patients who are currently at imminent risk of harm to self or others will be excluded;
• Any major surgery within three months of the Baseline Visit or any minor surgery within one month;
• Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal, gastrointestinal or metabolic dysfunction unless currently controlled and stable; Uncontrolled diabetes mellitus defined as HbA1c >7% or fasting glucose levels >130 mg/dL; Positive hepatitis C antibody test (anti-HCV); Positive hepatitis B surface antigen (HBsAg);
• History (including family history) or current evidence of congenital long QT syndrome or known acquired QT interval prolongation;
• Exposure to any investigational medication, including placebo, within 60 days of the Baseline Visit;
• Exposure (within 2 weeks of the Baseline Visit) to any over-the-counter medications including melatonin, dietary supplements and/or herbal remedies;
• Treatment with any medication known to cause major organ system toxicity (e.g., chloramphenicol or tamoxifen) during the 60 days preceding the Screening visit;
• History of intolerance and/or hypersensitivity to medications similar to VLY-686 and its accompanying excipients; Participation in a previous LY686017 or VLY-686 trial;
• Significant illness within the two weeks prior to the Baseline Visit;
• Pregnant or lactating females;
• Have a history of cirrhosis or laboratory evidence of hepatocellular injury, as evidenced by elevated levels of serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) greater than 2 times the upper limit of normal (2X ULN);
• Not willing to accept information-transfer concerning participation in the study, or information regarding his/her health (e.g. laboratory results or medical history);
• Anyone affiliated with the site or sponsor and/or anyone who may consent under duress;
• Any other sound medical reason as determined by the clinical Investigator.