A Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics and Exploratory Clinical Activity of NM26-2198 in Healthy Subjects and in Patients With Moderate-to-severe Atopic Dermatitis (AD)

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, single- and multiple ascending dose study of subcutaneous (SC) administration of NM26-2198 in healthy Japanese and non-Asian volunteers and adult patients with moderate to-severe AD to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single (SAD) and multiple doses (MAD) of NM26-2198.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics and Exploratory Clinical Activity of NM26-2198 in Healthy Japanese and Non-Asian Volunteers and in Adult Patients With Atopic Dermatitis

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Biological: NM26-2198
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SAD: Non-Asian ethnicity with grandparents and parents of non-Asian descent or Japanese descent having all four Japanese grandparents born in Japan. SAD: Male or female aged 18 to 55 years; MAD: Male or female ≥18 years of age. Weight of 45 kg to 100 kg and BMI of 18.0 to 30.0 kg/m2. SAD: Non-childbearing, non-breastfeeding females or males willing to use double barrier contraception or abstention from sex and sperm donation during the study; MAD: Males willing to use double barrier contraception or abstention from sex and sperm donation during the study; non-childbearing females or females of childbearing potential using protocol-defined method contraception, and who is not pregnant, lactating, or breastfeeding. MAD: Diagnosis of chronic AD. MAD: EASI score ≥16. MAD: vIGA-AD™ score of ≥3. MAD: Atopic lesions cover ≥10% of body surface area (BSA). MAD: PP-NRS score ≥4. MAD: Daily use of non-prescription emollient. Note: Other protocol-defined Inclusion criteria apply. Exclusion Criteria: SAD: Any clinically-relevant medical history or lab abnormality, including positive test for SARS-CoV-2, Hepatitis B or C, or HIV; MAD: Clinically-significant, abnormal laboratory findings, or positive test for SARS-CoV-2, Hepatitis B or C, or HIV. Clinically important ECG abnormalities or history/evidence thereof. SAD: Use of prescription or non-prescription medications (except occasional use of paracetamol). MAD: Diagnosis of protocol-specified skin diseases other than AD, or history of other significant skin condition that could interfere with study assessments. MAD: History or ongoing allergy/hypersensitivity or history, or history of hypersensitivity to biological drugs. MAD: Recent receipt of immunoglobulin or blood products. MAD: Recent treatment with protocol-specified investigational treatments, or any prior treatment with dupilumab, tralokinumab, lebrikizumab, nemolizumab, or other protocol-specified drugs. MAD: AD with recent ocular involvement requiring chronic ocular corticosteroid treatment. MAD: Chronic pruritis due to conditions other than AD. MAD: Acute AD superinfection, recent superficial skin infection, or other chronic/acute infection requiring protocol-defined treatments. MAD: Recent use of sedating antihistimines, systemic corticosteroids, cytotoxic treatments, other immunosuppressive/immunomodulating agents, and other protocol-specified prohibited medications. MAD: Recent topical corticosteroid or prescription moisturizer use. Note: Other protocol-defined Exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo (for NM26-2198) for subcutaneous (SC) injection on Day 1 (SAD and MAD), Day 8 (MAD only), Day 15 (MAD only), and Day 22 (MAD only). | Other: Placebo<br>* Placebo for NM26-2198<br>|
| Experimental: NM26-2198 10 mg<br>NM26-2198 10 mg for SC injection on Day 1 (SAD) | Biological: NM26-2198<br>* IL-4R/IL-31 bispecific antibody for subcutaneous administration<br>|
| Experimental: NM26-2198 50 mg<br>NM26-2198 50 mg for SC injection on Day 1 (SAD) | Biological: NM26-2198<br>* IL-4R/IL-31 bispecific antibody for subcutaneous administration<br>|
| Experimental: NM26-2198 150 mg<br>NM26-2198 150 mg for SC injection on Day 1 (SAD) | Biological: NM26-2198<br>* IL-4R/IL-31 bispecific antibody for subcutaneous administration<br>|
| Experimental: NM26-2198 300 mg<br>NM26-2198 300 mg for SC injection on Day 1 (SAD) | Biological: NM26-2198<br>* IL-4R/IL-31 bispecific antibody for subcutaneous administration<br>|
| Experimental: NM26-2198 400 mg<br>NM26-2198 400 mg for SC injection on Day 1 (SAD) | Biological: NM26-2198<br>* IL-4R/IL-31 bispecific antibody for subcutaneous administration<br>|
| Experimental: NM26-2198 600 mg<br>NM26-2198 600 mg for SC injection on Day 1 (SAD) | Biological: NM26-2198<br>* IL-4R/IL-31 bispecific antibody for subcutaneous administration<br>|
| Experimental: NM26-2198<br>NM26-2198 for SC injection on Days 1, 8, 15, and 22 (MAD). Doses to be determined based on observed safety and tolerability from SAD. | Biological: NM26-2198<br>* IL-4R/IL-31 bispecific antibody for subcutaneous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with Treatment Emergent Adverse Events (TEAEs) [SAD] | TEAEs defined as AEs and SAEs developing or worsening during treatment period (time from the first dose of study drug up to the end of study visit [Day 57 in SAD]), and includes findings from vital signs, electrocardiogram (ECG), clinical laboratory tests, physical examinations, and injection site evaluations. | First dose through end of study (Day 57) | 
| Percentage of participants with Treatment Emergent Adverse Events (TEAEs) [MAD] | TEAEs defined as AEs and SAEs developing or worsening during treatment period (time from the first dose of study drug up to the end of study visit [Day 85 in MAD]), and includes findings from vital signs, electrocardiogram (ECG), clinical laboratory tests, physical examinations, and injection site evaluations. | First dose through end of study (Day 85) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [SAD] | Mean maximum concentration of NM26-2198 after single dose administration in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [MAD] | Mean maximum concentration of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Trough Concentration (Ctrough) [MAD] | Mean trough concentrations of NM26-2198 with multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [SAD] | Mean time of maximum concentration of NM26-2198 after single dose administration in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [MAD] | Mean time of maximum concentration of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Last Area Under the Curve (AUClast) [SAD] | Mean area under the curve from the time of dosing to the last measurable concentration of NM26-2198 after single dose administration in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Last Area Under the Curve (AUClast) [MAD] | Mean area under the curve from the time of dosing to the last measurable concentration of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Area Under the Curve During the Dosing Interval (AUCtau) [SAD] | Mean area under concentration-time curve over dosing interval of NM26-2198 after single dose administration in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Area Under the Curve During the Dosing Interval (AUCtau) [MAD] | Mean area under concentration-time curve over dosing interval of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [SAD] | Mean estimated total exposure to NM26-2198 after single dose administration in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [MAD] | Mean estimated total exposure to NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [SAD] | Mean time-averaged concentration of NM26-2198 after single dose administration in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [MAD] | Mean time-averaged concentration of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [SAD] | Mean terminal elimination rate of NM26-2198 after single dose administrations in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [MAD] | Mean terminal elimination rate of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Half-Life (t1/2) [SAD] | Mean half-life of NM26-2198 after single dose administration in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Half-Life (t1/2) [MAD] | Mean terminal elimination rate of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Clearance (CL/F) [SAD] | Mean clearance of NM26-2198 after single dose administration in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Clearance (CL/F) [MAD] | Mean clearance of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Volume of Distribution (Vz/F) [MAD] | Mean volume of distribution of NM26-2198 after single dose administrations in healthy subjects. | Pre-dose on Day 1 through Day 57 | 
| Pharmacokinetics of NM26-2198: Volume of Distribution (Vz/F) [MAD] | Mean volume of distribution of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Accumulation Ratio for Cmax (Racc,cmax) [MAD] | Mean accumulation ratio for Cmax of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Pharmacokinetics of NM26-2198: Accumulation Ratio for AUCtau (Racc,AUCtau) [MAD] | Mean accumulation ratio for AUCtau of NM26-2198 after multiple dose administrations in patients with AD. | Pre-dose on Day 1 through Day 85 | 
| Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [SAD] |  | Pre-dose on Day 1 through Day 57 | 
| Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [MAD] |  | Pre-dose on Day 1 through Day 85 | 
| Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [SAD] |  | Pre-dose on Day 1 through Day 57 | 
| Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [MAD] |  | Pre-dose on Day 1 through Day 85 | 
| Mean ADA titers [SAD] |  | Pre-dose on Day 1 through Day 57 | 
| Mean ADA titers [MAD] |  | Pre-dose on Day 1 through Day 85 |