Clinical trial NCT05859724: Evaluation of NM26-2198 in Healthy Subjects and in Patients With Moderate-to-severe Atopic Dermatitis (AD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Atopic Dermatitis
Lead sponsor: Yellow Jersey Therapeutics AG
Sponsor class: INDUSTRY
First posted: 2023-05-16
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of participants with Treatment Emergent Adverse Events (TEAEs) [SAD]
timeFrame: First dose through end of study (Day 57)
measure: Percentage of participants with Treatment Emergent Adverse Events (TEAEs) [MAD]
timeFrame: First dose through end of study (Day 85)
Secondary outcomes:
measure: Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Trough Concentration (Ctrough) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Last Area Under the Curve (AUClast) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Pharmacokinetics of NM26-2198: Last Area Under the Curve (AUClast) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Area Under the Curve During the Dosing Interval (AUCtau) [SAD]
timeFrame: Pre-dose on Day 1 through Day 7
measure: Pharmacokinetics of NM26-2198: Area Under the Curve During the Dosing Interval (AUCtau) [MAD]
timeFrame: Pre-dose on Day 1 through Day 29
measure: Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Time of last quantifiable concentration (tlast) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Pharmacokinetics of NM26-2198: Time of last quantifiable concentration (tlast) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Terminal elimination half-life (t1/2) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Pharmacokinetics of NM26-2198: Terminal elimination half-life (t1/2) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Pharmacokinetics of NM26-2198: Total body clearance (CL/F) [SAD]
timeFrame: Day 1
measure: Pharmacokinetics of NM26-2198: Total body clearance (CL/F) [MAD]
timeFrame: Day 1 and Day 22
measure: Pharmacokinetics of NM26-2198: Apparent volume of distribution (Vz/F) [SAD]
timeFrame: Day 1
measure: Pharmacokinetics of NM26-2198: Apparent volume of distribution (Vz/F) [MAD]
timeFrame: Day 1 and Day 22
measure: Pharmacokinetics of NM26-2198: Accumulation ratio of last dose Cmax (Racc,cmax) [MAD]
timeFrame: Day 1 through Day 22
measure: Pharmacokinetics of NM26-2198: Accumulation ratio of last dose AUCtau (Racc,AUCtau) [MAD]
timeFrame: Day 1 through Day 22
measure: Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
measure: Mean ADA titers [SAD]
timeFrame: Pre-dose on Day 1 through Day 57
measure: Mean ADA titers [MAD]
timeFrame: Pre-dose on Day 1 through Day 85
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: First OC Dermatology Research
state: California
city: Glendale
country: United States
facility: California Clinical Trials Medical Group (CCTMG) managed by Parexel
state: California
city: San Diego
country: United States
facility: TCR Medical Corporation
state: California
city: Tamarac
country: United States
facility: D&H Tamarac Research Center
state: Florida
city: New York
country: United States
facility: Sadick Research Group
state: New York
city: Philadelphia
country: United States
facility: Paddington Testing Co.
state: Pennsylvania
city: London
country: Canada
facility: DermEffects
state: Ontario
city: Québec
country: Canada
facility: Centre de Recherche Saint-Louis
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
state: Hessen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Lübeck
country: Germany
facility: UK-SH - Lübeck
state: Schleswig-Holstein
city: Gdansk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o.o., Szpital Sw. Wojciecha
city: Rzeszów
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. F.Chopina w Rzeszowie
city: Warszawa
country: Poland
facility: Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych
city: Warszawa
country: Poland
facility: Klinika Ambroziak Dermatologia
Study officials:
affiliation: Yellow Jersey Therapeutics AG
name: Yellow Jersey Therapeutics AG Clinical trial
role: STUDY_DIRECTOR
References: