Atopic Dermatitis
Conditions
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.
Interventions
BIOLOGICALNM26-2198
IL-4R/IL-31 bispecific antibody for subcutaneous administration
OTHERPlacebo
Placebo for NM26-2198
Sponsors
Yellow Jersey Therapeutics AG
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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) [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: 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: 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: 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: 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: 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) [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: 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) [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: 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 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: 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: 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: 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: 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: 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. |
| 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: 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. |
| 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. |
| 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-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 | — |
Countries
Canada, Germany, Poland, United States
Contacts
STUDY_DIRECTORYellow Jersey Therapeutics AG Clinical trial
Yellow Jersey Therapeutics AG
Outcome results
None listed