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

Atopic Dermatitis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05859724
• Other study ID #: NB-NM026-2198-101
• Secondary ID: 2023-503577-38
• Status: Recruiting
• Phase: Phase 1
• Start date: May 10, 2023
• Est. completion date: April 4, 2025

Study information

• Verified date: March 2024
• Source: Numab Therapeutics AG
• Contact: Peter Lichtlen, MD, PhD, BBA
• Phone: +41-44-533-22-92
• Email: clinicaltrials[@]numab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: April 4, 2025
• Est. primary completion date: February 3, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Biological:
• NM26-2198
IL-4R/IL-31 bispecific antibody for subcutaneous administration

Other:
• Placebo
Placebo for NM26-2198

Locations

Country	Name	City	State
Canada	Alberta DermaSurgery Centre	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	DermEffects	London	Ontario
Canada	Centre de Recherche Saint-Louis	Québec
Germany	Universitätsklinikum Bonn AöR	Bonn	Nordrhein-Westfalen
Germany	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen
Germany	Universitätsklinikum Frankfurt am Main - Klinik für Dermatology	Frankfurt	Hessen
Germany	UK-SH - Lübeck	Lübeck	Schleswig-Holstein
Germany	Universitätsmedizin Mainz	Mainz	Hessen
Poland	COPERNICUS Podmiot Leczniczy Sp. z o.o., Szpital Sw. Wojciecha	Gdansk
Poland	Uniwersytecki Szpital Kliniczny im. F.Chopina w Rzeszowie	Rzeszów
Poland	Klinika Ambroziak Dermatologia	Warszawa
Poland	Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych	Warszawa
United States	Annexus Dermatology & Aesthetics	DeLand	Florida
United States	First OC Dermatology Research	Fountain Valley	California
United States	Center for Dermatology Clinical Research	Fremont	California
United States	California Clinical Trials Medical Group (CCTMG) managed by Parexel	Glendale	California
United States	UCLA Department of Medicine	Los Angeles	California
United States	Sadick Research Group	New York	New York
United States	Paddington Testing Co.	Philadelphia	Pennsylvania
United States	TCR Medical Corporation	San Diego	California
United States	D&H Tamarac Research Center	Tamarac	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Numab Therapeutics AG	Kaken Pharmaceutical Co., Ltd.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Pharmacokinetics of NM26-2198: Terminal Elimination Rate (?z) [SAD]	Mean terminal elimination rate of NM26-2198 after single dose administrations in healthy subjects.	Pre-dose on Day 1 through Day 57
Secondary	Pharmacokinetics of NM26-2198: Terminal Elimination Rate (?z) [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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [SAD]		Pre-dose on Day 1 through Day 57
Secondary	Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [MAD]		Pre-dose on Day 1 through Day 85
Secondary	Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [SAD]		Pre-dose on Day 1 through Day 57
Secondary	Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [MAD]		Pre-dose on Day 1 through Day 85
Secondary	Mean ADA titers [SAD]		Pre-dose on Day 1 through Day 57
Secondary	Mean ADA titers [MAD]		Pre-dose on Day 1 through Day 85