Safety, Tolerability and PK of ATTO-1310 in Healthy Volunteers and Patients With Atopic Dermatitis and Patients With Chronic Pruritus

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.

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