safety, tolerability and pk of atto-1310 in healthy volunteers and patients with atopic dermatitis and patients with chronic pruritus

Conditions: Normal Volunteers; Atopic Dermatitis (AD); Atopic Eczema; Chronic Pruritus

Summary: the goal of this clinical trial is to assess the safety, tolerability, and pharmacokinetics of atto-1310 in healthy adults, patients with atopic dermatitis and patients with chronic pruritus. the main questions it aims to answer are: what medical problems do participants have when taking atto-1310? how long does atto-1310 stay in the body after dosing? researchers will compare atto-1310 to a placebo (a look-alike substance that contains no drug). participants will be dosed with atto-1310 or a placebo, visit the clinic for checkups and tests, and keep a diary of their symptoms.

this is a 4-part study. parts 1 and 2 will be a single and multiple ascending dose design, respectively, assessing the safety, tolerability and pk of atto-1310 in healthy adult volunteers. part 3 and part 4 will consist of a single dose in adult patients with atopic dermatitis or chronic pruritus, respectively, to assess safety, tolerability, pk, and pd based on biomarkers in the blood.

Eligibility criteria:
parts 1 \& 2 (healthy volunteers) key inclusion criteria: * any sex or gender who is 18 to 65 years old * body weight of 50 to 125 kg and body mass index (bmi) between 18.5 and 35 kg/m2 * considered in good general health based on medical history, physical exam, 12-lead ecg, screening clinical laboratory findings, and vital signs * negative pregnancy test for subjects of child-bearing potential * use of highly effective forms of birth control part 3 (subjects with atopic dermatitis) inclusion criteria: * any sex or gender who is 18 to 65 years old * body weight of 50 to 125 kg and bmi between 18.5 and 40 kg/m2 * clinically confirmed diagnosis of active ad * at least a 1-year history of ad and had no significant flares in ad for at least 4 weeks before screening * baseline weekly mean of daily pp-nrs ≥ 7 at day 1 * easi score of ≥ 7 at screening and day 1 * viga-ad score of ≥ 3 at screening and day 1 * use of topical bland emollient (moisturizer) once or twice daily for at least 5 of the 7 days immediately before day 1 and agrees to continue using that same emollient at the same frequency throughout the study * negative pregnancy test for subjects of child-bearing potential * use of highly effective forms of birth control part 4 (subjects with chronic pruritus) inclusion criteria: * any sex or gender who is 18 to 85 years old * body weight of 50 to 125 kg, inclusive, and bmi between 18.5 and 40 kg/m2 * has had chronic pruritus for at least 6 months and is unresponsive to at least a 2-week course of emollient use. * chronic pruritus that affects at least 2 of the following body areas: legs, arms, or trunk * a single pp-nrs score of ≥ 5 in the 24-hour period prior to the screening visit * baseline weekly mean of daily pp-nrs ≥ 7 at day 1 * use of a stable dose of topical bland emollient (moisturizer) once or twice daily for at least 2 weeks before day 1 and agrees to continue using that same emollient at the same frequency throughout the study * negative pregnancy test for subjects of child-bearing potential * use of highly effective forms of birth control parts 1 \& 2 (healthy volunteers) exclusion criteria: * any clinically significant underlying illness. * history of malignancy within 5 years of screening, except adequately treated basal carcinoma or in situ carcinoma of the cervix. * history of major surgery within 8 weeks prior to day 1 * history of asthma requiring regular use of a bronchodilator or a daily maintenance therapy * history of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the ip excipients (sucrose, polysorbate 80, or histidine) * active hepatitis b virus (hbv) or hepatitis c virus (hcv) or is positive for hiv * active or latent tuberculosis infection * smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent) per day * history of drug or alcohol abuse * laboratory values outside of the normal range exclusion criteria for part 3 (subjects with atopic dermatitis): * any clinically significant underlying illness * history of a clearly defined etiology for pruritus other than ad, including but not limited to urticaria, psoriasis, or other non-atopic dermatologic conditions, hepatic or renal disease, psychogenic pruritus, drug reaction, uncontrolled hyperthyroidism, and infection * history of malignancy within 5 years of screening * history of major surgery within 8 weeks prior to day 1 or has a major surgery planned during the study * history of asthma requiring regular use of a bronchodilator or a daily maintenance therapy * history of recurrent eczema herpeticum * history of known primary immunodeficiency, is considered immunocompromised, history of untreated latent tuberculosis infection, has been treated for active tuberculosis in the past year, or has been treated for a parasitic infection in the past 6 months * history of major depression * history of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the ip excipients (sucrose, polysorbate 80, or histidine) * active hbv or hcv or is positive for hiv * smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent) per day * ecg with a qtcf \> 450 msec for males or \> 470 msec for females at screening * history of drug or alcohol abuse * subject has applied topical corticosteroid in the 14 days preceding day 1 * subject has used prohibited medications or therapies during the specified washout period before day 1 (as defined in the protocol) * laboratory values outside of the normal range exclusion criteria for part 4 (subjects with chronic pruritus): * primary dermatologic diagnosis associated with pruritic skin lesions at the time of screening * regional neuropathic disease associated with pruritus * severe renal failure requiring dialysis * untreated cholestatic liver disease * liver function tests (bilirubin, ast, alt, alkaline phosphatase) \>2.5 times above the upper limit of normal * history of infectious dermatoses * suspected diagnosis of somatoform pruritus * suspected diagnosis of drug-induced pruritus * history of malignancy within 5 years of screening * history of unexplained fevers, night sweats, or unintentional weight loss * major surgery within 8 weeks prior to day 1 or has a major surgery planned during the study * history of asthma requiring regular use of a bronchodilator or a daily maintenance therapy * history of known primary immunodeficiency, is considered immunocompromised, untreated latent tuberculosis infection, has been treated for active tuberculosis in the past year, or has been treated for a parasitic infection in the past 6 months * history of attempted suicide * history of hypersensitivity (including anaphylaxis) to a biologic medication, vaccine, an immunoglobulin product (plasma-derived or recombinant, eg, monoclonal antibody), or to any of the ip excipients (sucrose, polysorbate 80, or histidine) * active hbv or hcv or is positive for hiv. * smoking more than 20 cigarettes (or cigars, cigarillos, or e-cigarettes equivalent) per day * ecg with a qtcf \> 450 msec for males or \> 470 msec for females at screening * history of drug or alcohol abuse * use of prohibited medications as defined in the protocol

Keywords: atopic dermatitis ad atopic eczema eczema chronic pruritis itch pruritus