Evaluation of NM26-2198 in Healthy Subjects and in Patients With Moderate-to-severe Atopic Dermatitis (AD)

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 Volunteers and in Adult Patients With Atopic Dermatitis

This is a randomized, double-blind, placebo-controlled, single- and multiple ascending dose study of subcutaneous (SC) administration of NM26-2198 in healthy 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.

Study Overview

• Status: Terminated
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Other: Placebo; Biological: NM26-2198

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1W4R4
    • Centre de Recherche Saint-Louis
  • Ontario
    • London, Ontario, Canada, N6H5L5
      • DermEffects
• Germany
  • Hesse
    • Mainz, Hesse, Germany, 55131
      • Universitätsmedizin Mainz
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitätsklinikum Carl Gustav Carus
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • UK-SH - Lübeck
• Poland
  • Gdansk, Poland, 80-462
    • COPERNICUS Podmiot Leczniczy Sp. z o.o., Szpital Sw. Wojciecha
  • Rzeszów, Poland, 35-055
    • Uniwersytecki Szpital Kliniczny im. F.Chopina w Rzeszowie
  • Warsaw, Poland, 02-953
    • Klinika Ambroziak Dermatologia
  • Warsaw, Poland, 02-507
    • Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • First OC Dermatology Research
    • Glendale, California, United States, 91206
      • California Clinical Trials Medical Group (CCTMG) managed by Parexel
    • San Diego, California, United States, 92123
      • TCR Medical Corporation
  • Florida
    • Tamarac, Florida, United States, 33321
      • D&H Tamarac Research Center
  • New York
    • New York, New York, United States, 10075
      • Sadick Research Group
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Co.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. SAD: Non-Asian ethnicity with grandparents and parents of non-Asian descent or Japanese descent having all four Japanese grandparents born in Japan.
2. SAD and MAD in Healthy Volunteers: Male or female aged 18 to 55 years; MAD: Male or female ≥18 years of age.
3. ALL COHORTS: Weight of 45 kg to 100 kg and BMI of 18.0 to 30.0 kg/m2.
4. SAD and MAD in Healthy Volunteers: 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.
5. MAD: Diagnosis of chronic AD.
6. MAD: EASI score ≥16.
7. MAD: vIGA-AD™ score of ≥3.
8. MAD: Atopic lesions cover ≥10% of body surface area (BSA).
9. MAD: PP-NRS score ≥4.
10. MAD: Daily use of non-prescription emollient.

Note: Other protocol-defined Inclusion criteria apply.

Exclusion Criteria:

1. SAD and MAD in Healthy Volunteers: 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.
2. ALL COHORTS: Clinically important ECG abnormalities or history/evidence thereof.
3. SAD and MAD in Healthy Volunteers: Use of prescription or non-prescription medications (except occasional use of paracetamol).
4. MAD: Diagnosis of protocol-specified skin diseases other than AD, or history of other significant skin condition that could interfere with study assessments.
5. MAD: History or ongoing allergy/hypersensitivity or history, or history of hypersensitivity to biological drugs.
6. MAD: Recent receipt of immunoglobulin or blood products.
7. MAD: Recent treatment with protocol-specified investigational treatments, or any prior treatment with dupilumab, tralokinumab, lebrikizumab, nemolizumab, or other protocol-specified drugs.
8. MAD: AD with recent ocular involvement requiring chronic ocular corticosteroid treatment.
9. MAD: Chronic pruritis due to conditions other than AD.
10. MAD: Acute AD superinfection, recent superficial skin infection, or other chronic/acute infection requiring protocol-defined treatments.
11. MAD: Recent use of sedating antihistimines, systemic corticosteroids, cytotoxic treatments, other immunosuppressive/immunomodulating agents, and other protocol-specified prohibited medications.
12. MAD: Recent topical corticosteroid or prescription moisturizer use.

Note: Other protocol-defined Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (for NM26-2198) for subcutaneous (SC) injection in healthy volunteers (HVs) on Day 1 (SAD Cohorts) and on Days 1, 8, 15, and 22 (MAD Cohorts)	Other: Placebo; Placebo for NM26-2198
Experimental: NM26-2198; NM26-2198 10mg, 50mg, 150mg, 300mg, 400mg, 600mg, and 900mg for SC injection in HVs on Day 1 (SAD Part A); NM26-2198 150mg and 300mg for SC injection in patients with AD on Days 1, 8, 15, and 22 (MAD Part B); NM26-2198 150mg and 300mg for SC injection in HVs on Days 1, 8, 15, and 22 (MAD Part C)	Biological: NM26-2198; IL-4R/IL-31 bispecific antibody for subcutaneous administration

What is the study measuring?

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: 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: 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: 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: 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: 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
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
Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [MAD]	Mean maximum concentration of NM26-2198 after multiple dose administrations in healthy volunteers and 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 healthy volunteers and in patients with AD.	Pre-dose on Day 1 through Day 85
Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [MAD]	Mean time of maximum concentration of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Pre-dose on Day 1 through Day 85
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 healthy volunteers and 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 7
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 healthy volunteers and in patients with AD.	Pre-dose on Day 1 through Day 29
Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [MAD]	Mean estimated total exposure to NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Pre-dose on Day 1 through Day 85
Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [MAD]	Mean time-averaged concentration of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Pre-dose on Day 1 through Day 85
Pharmacokinetics of NM26-2198: Time of last quantifiable concentration (tlast) [SAD]	Mean estimated time to last quantificable 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 last quantifiable concentration (tlast) [MAD]	Mean estimated time to last quantificable concentration of NM26-2198 after multiple dose administration in healthy volunteers and in patients with AD.	Pre-dose on Day 1 through Day 85
Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [MAD]	Mean terminal elimination rate of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Pre-dose on Day 1 through Day 85
Pharmacokinetics of NM26-2198: Terminal elimination half-life (t1/2) [SAD]	Mean terminal elimination half-life of NM26-2198 after single dose administration in healthy subjects.	Pre-dose on Day 1 through Day 57
Pharmacokinetics of NM26-2198: Terminal elimination half-life (t1/2) [MAD]	Mean terminal elimination half-life of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Pre-dose on Day 1 through Day 85
Pharmacokinetics of NM26-2198: Total body clearance (CL/F) [SAD]	Mean total body clearance of NM26-2198 after single dose administration in healthy subjects.	Day 1
Pharmacokinetics of NM26-2198: Total body clearance (CL/F) [MAD]	Mean total body clearance of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Day 1 and Day 22
Pharmacokinetics of NM26-2198: Apparent volume of distribution (Vz/F) [SAD]	Mean apparent volume of distribution of NM26-2198 after single dose administrations in healthy subjects.	Day 1
Pharmacokinetics of NM26-2198: Apparent volume of distribution (Vz/F) [MAD]	Mean apparent volume of distribution of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Day 1 and Day 22
Pharmacokinetics of NM26-2198: Accumulation ratio of last dose Cmax (Racc,cmax) [MAD]	Mean accumulation ratio of last dose Cmax of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Day 1 through Day 22
Pharmacokinetics of NM26-2198: Accumulation ratio of last dose AUCtau (Racc,AUCtau) [MAD]	Mean accumulation ratio of last dose AUCtau of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.	Day 1 through Day 22

Collaborators and Investigators

• Sponsor: Yellow Jersey Therapeutics AG
• Collaborators: Kaken Pharmaceutical Co., Ltd.
• Investigators: Study Director: Yellow Jersey Therapeutics AG Clinical trial, Yellow Jersey Therapeutics AG

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2023
• Primary Completion (Actual): October 1, 2024
• Study Completion (Actual): October 17, 2024

Study Registration Dates

• First Submitted: May 5, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Dermatitis, Atopic
• Other Study ID Numbers: NB-NM026-2198-101; 2023-503577-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No