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

Phase 1TerminatedNCT05859724

Yellow Jersey Therapeutics AG126 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

126

Conditions

Atopic Dermatitis

Interventions

NM26-2198BIOLOGICAL

IL-4R/IL-31 bispecific antibody for subcutaneous administration

PlaceboOTHER

Placebo for NM26-2198

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (15)

First OC Dermatology Research

Fountain Valley, California, United States

California Clinical Trials Medical Group (CCTMG) managed by Parexel

Glendale, California, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: First dose through end of study (Day 85)

Secondary Outcomes

Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [SAD]

Mean maximum concentration of NM26-2198 after single dose administration in healthy subjects.

Time frame: 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 healthy volunteers and in patients with AD.

Time frame: 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.

Time frame: Pre-dose on Day 1 through Day 85

Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [SAD]

Data from ClinicalTrials.gov

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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, Hesse, Germany

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, Germany

...and 5 more locations

Mean time of maximum concentration of NM26-2198 after single dose administration in healthy subjects.

Time frame: 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 healthy volunteers and in patients with AD.

Time frame: 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.

Time frame: 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 healthy volunteers and in patients with AD.

Time frame: 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.

Time frame: 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.

Time frame: Pre-dose on Day 1 through Day 29

Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [SAD]

Mean estimated total exposure to NM26-2198 after single dose administration in healthy subjects.

Time frame: 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 healthy volunteers and in patients with AD.

Time frame: 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.

Time frame: 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 healthy volunteers and in patients with AD.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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 healthy volunteers and in patients with AD.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Day 1 through Day 22

Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [SAD]

Time frame: Pre-dose on Day 1 through Day 57

Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [MAD]

Time frame: Pre-dose on Day 1 through Day 85

Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [SAD]

Time frame: Pre-dose on Day 1 through Day 57

Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [MAD]

Time frame: Pre-dose on Day 1 through Day 85

Mean ADA titers [SAD]

Time frame: Pre-dose on Day 1 through Day 57

Mean ADA titers [MAD]

Time frame: Pre-dose on Day 1 through Day 85