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

Phase 1

Terminated

• Conditions: Atopic Dermatitis
• Interventions: Biological: NM26-2198; Other: Placebo

• Registration Number: NCT05859724
• Lead Sponsor: Yellow Jersey Therapeutics AG

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-05
• Study First Submitted QC: 2023-05-05
• Study Start: 2023-05-10
• Study First Posted: 2023-05-16
• Primary Completion: 2024-10-01
• Study Completion: 2024-10-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-28
• Last Update Posted: 2025-04-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 126

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
NM26-2198	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)
Placebo	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)

Primary Outcome Measures

Name	Time	Method
Percentage of participants with Treatment Emergent Adverse Events (TEAEs) [MAD]	First dose through end of study (Day 85)	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.
Percentage of participants with Treatment Emergent Adverse Events (TEAEs) [SAD]	First dose through end of study (Day 57)	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.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [SAD]	Pre-dose on Day 1 through Day 57	Mean maximum concentration of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [MAD]	Pre-dose on Day 1 through Day 85	Mean maximum concentration of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [SAD]	Pre-dose on Day 1 through Day 57	Mean estimated total exposure to NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Trough Concentration (Ctrough) [MAD]	Pre-dose on Day 1 through Day 85	Mean trough concentrations of NM26-2198 with multiple dose administrations in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [MAD]	Pre-dose on Day 1 through Day 85	Mean time of maximum concentration of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Area Under the Curve During the Dosing Interval (AUCtau) [MAD]	Pre-dose on Day 1 through Day 29	Mean area under concentration-time curve over dosing interval of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [MAD]	Pre-dose on Day 1 through Day 85	Mean estimated total exposure to NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [MAD]	Pre-dose on Day 1 through Day 85	Mean time-averaged concentration of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Time of last quantifiable concentration (tlast) [SAD]	Pre-dose on Day 1 through Day 57	Mean estimated time to last quantificable concentration of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Time of last quantifiable concentration (tlast) [MAD]	Pre-dose on Day 1 through Day 85	Mean estimated time to last quantificable concentration of NM26-2198 after multiple dose administration in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Terminal elimination half-life (t1/2) [SAD]	Pre-dose on Day 1 through Day 57	Mean terminal elimination half-life of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [SAD]	Pre-dose on Day 1 through Day 57	Mean time of maximum concentration of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Last Area Under the Curve (AUClast) [MAD]	Pre-dose on Day 1 through Day 85	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.
Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [SAD]	Pre-dose on Day 1 through Day 57	Mean terminal elimination rate of NM26-2198 after single dose administrations in healthy subjects.
Pharmacokinetics of NM26-2198: Total body clearance (CL/F) [SAD]	Day 1	Mean total body clearance of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Last Area Under the Curve (AUClast) [SAD]	Pre-dose on Day 1 through Day 57	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.
Pharmacokinetics of NM26-2198: Area Under the Curve During the Dosing Interval (AUCtau) [SAD]	Pre-dose on Day 1 through Day 7	Mean area under concentration-time curve over dosing interval of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Total body clearance (CL/F) [MAD]	Day 1 and Day 22	Mean total body clearance of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [SAD]	Pre-dose on Day 1 through Day 57
Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [SAD]	Pre-dose on Day 1 through Day 57
Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [SAD]	Pre-dose on Day 1 through Day 57	Mean time-averaged concentration of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Apparent volume of distribution (Vz/F) [MAD]	Day 1 and Day 22	Mean apparent volume of distribution of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [MAD]	Pre-dose on Day 1 through Day 85
Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [MAD]	Pre-dose on Day 1 through Day 85	Mean terminal elimination rate of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Apparent volume of distribution (Vz/F) [SAD]	Day 1	Mean apparent volume of distribution of NM26-2198 after single dose administrations in healthy subjects.
Pharmacokinetics of NM26-2198: Accumulation ratio of last dose AUCtau (Racc,AUCtau) [MAD]	Day 1 through Day 22	Mean accumulation ratio of last dose AUCtau of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
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
Pharmacokinetics of NM26-2198: Terminal elimination half-life (t1/2) [MAD]	Pre-dose on Day 1 through Day 85	Mean terminal elimination half-life of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Pharmacokinetics of NM26-2198: Accumulation ratio of last dose Cmax (Racc,cmax) [MAD]	Day 1 through Day 22	Mean accumulation ratio of last dose Cmax of NM26-2198 after multiple dose administrations in healthy volunteers and in patients with AD.
Mean ADA titers [MAD]	Pre-dose on Day 1 through Day 85

Trial Locations

Locations (15)

First OC Dermatology Research; 🇺🇸 Fountain Valley, California, United States

California Clinical Trials Medical Group (CCTMG) managed by Parexel; 🇺🇸 Glendale, California, United States

TCR Medical Corporation; 🇺🇸 San Diego, California, United States

D&H Tamarac Research Center; 🇺🇸 Tamarac, Florida, United States

Sadick Research Group; 🇺🇸 New York, New York, United States

Paddington Testing Co.; 🇺🇸 Philadelphia, Pennsylvania, United States

DermEffects; 🇨🇦 London, Ontario, Canada

Centre de Recherche Saint-Louis; 🇨🇦 Québec, Canada

Universitätsmedizin Mainz; 🇩🇪 Mainz, Hessen, Germany

Universitätsklinikum Carl Gustav Carus; 🇩🇪 Dresden, Sachsen, Germany

UK-SH - Lübeck; 🇩🇪 Lübeck, Schleswig-Holstein, Germany

COPERNICUS Podmiot Leczniczy Sp. z o.o., Szpital Sw. Wojciecha; 🇵🇱 Gdansk, Poland

Uniwersytecki Szpital Kliniczny im. F.Chopina w Rzeszowie; 🇵🇱 Rzeszów, Poland

Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych; 🇵🇱 Warszawa, Poland

Klinika Ambroziak Dermatologia; 🇵🇱 Warszawa, Poland