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A Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics and Exploratory Clinical Activity of NM26-2198 in Healthy Subjects and in Patients With Moderate-to-severe Atopic Dermatitis (AD)

Primary Purpose

Atopic Dermatitis

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
NM26-2198
Placebo
Sponsored by
Numab Therapeutics AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atopic Dermatitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: SAD: Non-Asian ethnicity with grandparents and parents of non-Asian descent or Japanese descent having all four Japanese grandparents born in Japan. SAD: Male or female aged 18 to 55 years; MAD: Male or female ≥18 years of age. Weight of 45 kg to 100 kg and BMI of 18.0 to 30.0 kg/m2. SAD: 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. MAD: Diagnosis of chronic AD. MAD: EASI score ≥16. MAD: vIGA-AD™ score of ≥3. MAD: Atopic lesions cover ≥10% of body surface area (BSA). MAD: PP-NRS score ≥4. MAD: Daily use of non-prescription emollient. Note: Other protocol-defined Inclusion criteria apply. Exclusion Criteria: SAD: 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. Clinically important ECG abnormalities or history/evidence thereof. SAD: Use of prescription or non-prescription medications (except occasional use of paracetamol). MAD: Diagnosis of protocol-specified skin diseases other than AD, or history of other significant skin condition that could interfere with study assessments. MAD: History or ongoing allergy/hypersensitivity or history, or history of hypersensitivity to biological drugs. MAD: Recent receipt of immunoglobulin or blood products. MAD: Recent treatment with protocol-specified investigational treatments, or any prior treatment with dupilumab, tralokinumab, lebrikizumab, nemolizumab, or other protocol-specified drugs. MAD: AD with recent ocular involvement requiring chronic ocular corticosteroid treatment. MAD: Chronic pruritis due to conditions other than AD. MAD: Acute AD superinfection, recent superficial skin infection, or other chronic/acute infection requiring protocol-defined treatments. MAD: Recent use of sedating antihistimines, systemic corticosteroids, cytotoxic treatments, other immunosuppressive/immunomodulating agents, and other protocol-specified prohibited medications. MAD: Recent topical corticosteroid or prescription moisturizer use. Note: Other protocol-defined Exclusion criteria apply.

Sites / Locations

  • California Clinical Trials Medical Group (CCTMG) managed by ParexelRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo

NM26-2198 10 mg

NM26-2198 50 mg

NM26-2198 150 mg

NM26-2198 300 mg

NM26-2198 400 mg

NM26-2198 600 mg

NM26-2198

Arm Description

Placebo (for NM26-2198) for subcutaneous (SC) injection on Day 1 (SAD and MAD), Day 8 (MAD only), Day 15 (MAD only), and Day 22 (MAD only).

NM26-2198 10 mg for SC injection on Day 1 (SAD)

NM26-2198 50 mg for SC injection on Day 1 (SAD)

NM26-2198 150 mg for SC injection on Day 1 (SAD)

NM26-2198 300 mg for SC injection on Day 1 (SAD)

NM26-2198 400 mg for SC injection on Day 1 (SAD)

NM26-2198 600 mg for SC injection on Day 1 (SAD)

NM26-2198 for SC injection on Days 1, 8, 15, and 22 (MAD). Doses to be determined based on observed safety and tolerability from SAD.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [SAD]
Mean maximum concentration of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [MAD]
Mean maximum concentration of NM26-2198 after multiple dose administrations in patients with AD.
Pharmacokinetics of NM26-2198: Trough Concentration (Ctrough) [MAD]
Mean trough concentrations of NM26-2198 with multiple dose administrations in patients with AD.
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.
Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [MAD]
Mean time of maximum concentration of NM26-2198 after multiple dose administrations in patients with AD.
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.
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 patients with AD.
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.
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 patients with AD.
Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [SAD]
Mean estimated total exposure to NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [MAD]
Mean estimated total exposure to NM26-2198 after multiple dose administrations in patients with AD.
Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [SAD]
Mean time-averaged concentration of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [MAD]
Mean time-averaged concentration of NM26-2198 after multiple dose administrations in patients with AD.
Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [SAD]
Mean terminal elimination rate of NM26-2198 after single dose administrations in healthy subjects.
Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [MAD]
Mean terminal elimination rate of NM26-2198 after multiple dose administrations in patients with AD.
Pharmacokinetics of NM26-2198: Half-Life (t1/2) [SAD]
Mean half-life of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Half-Life (t1/2) [MAD]
Mean terminal elimination rate of NM26-2198 after multiple dose administrations in patients with AD.
Pharmacokinetics of NM26-2198: Clearance (CL/F) [SAD]
Mean clearance of NM26-2198 after single dose administration in healthy subjects.
Pharmacokinetics of NM26-2198: Clearance (CL/F) [MAD]
Mean clearance of NM26-2198 after multiple dose administrations in patients with AD.
Pharmacokinetics of NM26-2198: Volume of Distribution (Vz/F) [MAD]
Mean volume of distribution of NM26-2198 after single dose administrations in healthy subjects.
Pharmacokinetics of NM26-2198: Volume of Distribution (Vz/F) [MAD]
Mean volume of distribution of NM26-2198 after multiple dose administrations in patients with AD.
Pharmacokinetics of NM26-2198: Accumulation Ratio for Cmax (Racc,cmax) [MAD]
Mean accumulation ratio for Cmax of NM26-2198 after multiple dose administrations in patients with AD.
Pharmacokinetics of NM26-2198: Accumulation Ratio for AUCtau (Racc,AUCtau) [MAD]
Mean accumulation ratio for AUCtau of NM26-2198 after multiple dose administrations in patients with AD.
Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [SAD]
Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [MAD]
Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [SAD]
Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [MAD]
Mean ADA titers [SAD]
Mean ADA titers [MAD]

Full Information

First Posted
May 5, 2023
Last Updated
May 15, 2023
Sponsor
Numab Therapeutics AG
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1. Study Identification

Unique Protocol Identification Number
NCT05859724
Brief Title
A Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics and Exploratory Clinical Activity 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 Japanese and Non-Asian Volunteers and in Adult Patients With Atopic Dermatitis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 10, 2023 (Anticipated)
Primary Completion Date
February 10, 2025 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Numab Therapeutics AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 Japanese and non-Asian 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
102 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo (for NM26-2198) for subcutaneous (SC) injection on Day 1 (SAD and MAD), Day 8 (MAD only), Day 15 (MAD only), and Day 22 (MAD only).
Arm Title
NM26-2198 10 mg
Arm Type
Experimental
Arm Description
NM26-2198 10 mg for SC injection on Day 1 (SAD)
Arm Title
NM26-2198 50 mg
Arm Type
Experimental
Arm Description
NM26-2198 50 mg for SC injection on Day 1 (SAD)
Arm Title
NM26-2198 150 mg
Arm Type
Experimental
Arm Description
NM26-2198 150 mg for SC injection on Day 1 (SAD)
Arm Title
NM26-2198 300 mg
Arm Type
Experimental
Arm Description
NM26-2198 300 mg for SC injection on Day 1 (SAD)
Arm Title
NM26-2198 400 mg
Arm Type
Experimental
Arm Description
NM26-2198 400 mg for SC injection on Day 1 (SAD)
Arm Title
NM26-2198 600 mg
Arm Type
Experimental
Arm Description
NM26-2198 600 mg for SC injection on Day 1 (SAD)
Arm Title
NM26-2198
Arm Type
Experimental
Arm Description
NM26-2198 for SC injection on Days 1, 8, 15, and 22 (MAD). Doses to be determined based on observed safety and tolerability from SAD.
Intervention Type
Biological
Intervention Name(s)
NM26-2198
Intervention Description
IL-4R/IL-31 bispecific antibody for subcutaneous administration
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo for NM26-2198
Primary Outcome Measure Information:
Title
Percentage of participants with Treatment Emergent Adverse Events (TEAEs) [SAD]
Description
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)
Title
Percentage of participants with Treatment Emergent Adverse Events (TEAEs) [MAD]
Description
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 Outcome Measure Information:
Title
Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [SAD]
Description
Mean maximum concentration of NM26-2198 after single dose administration in healthy subjects.
Time Frame
Pre-dose on Day 1 through Day 57
Title
Pharmacokinetics of NM26-2198: Peak Concentration (Cmax) [MAD]
Description
Mean maximum concentration of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Trough Concentration (Ctrough) [MAD]
Description
Mean trough concentrations of NM26-2198 with multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [SAD]
Description
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
Title
Pharmacokinetics of NM26-2198: Time of Peak Concentration (Tmax) [MAD]
Description
Mean time of maximum concentration of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Last Area Under the Curve (AUClast) [SAD]
Description
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
Title
Pharmacokinetics of NM26-2198: Last Area Under the Curve (AUClast) [MAD]
Description
Mean area under the curve from the time of dosing to the last measurable concentration of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Area Under the Curve During the Dosing Interval (AUCtau) [SAD]
Description
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 57
Title
Pharmacokinetics of NM26-2198: Area Under the Curve During the Dosing Interval (AUCtau) [MAD]
Description
Mean area under concentration-time curve over dosing interval of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [SAD]
Description
Mean estimated total exposure to NM26-2198 after single dose administration in healthy subjects.
Time Frame
Pre-dose on Day 1 through Day 57
Title
Pharmacokinetics of NM26-2198: Estimated Total Exposure (AUCinf) [MAD]
Description
Mean estimated total exposure to NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [SAD]
Description
Mean time-averaged concentration of NM26-2198 after single dose administration in healthy subjects.
Time Frame
Pre-dose on Day 1 through Day 57
Title
Pharmacokinetics of NM26-2198: Time-Averaged Concentration (AUC%extrap) [MAD]
Description
Mean time-averaged concentration of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [SAD]
Description
Mean terminal elimination rate of NM26-2198 after single dose administrations in healthy subjects.
Time Frame
Pre-dose on Day 1 through Day 57
Title
Pharmacokinetics of NM26-2198: Terminal Elimination Rate (λz) [MAD]
Description
Mean terminal elimination rate of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Half-Life (t1/2) [SAD]
Description
Mean half-life of NM26-2198 after single dose administration in healthy subjects.
Time Frame
Pre-dose on Day 1 through Day 57
Title
Pharmacokinetics of NM26-2198: Half-Life (t1/2) [MAD]
Description
Mean terminal elimination rate of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Clearance (CL/F) [SAD]
Description
Mean clearance of NM26-2198 after single dose administration in healthy subjects.
Time Frame
Pre-dose on Day 1 through Day 57
Title
Pharmacokinetics of NM26-2198: Clearance (CL/F) [MAD]
Description
Mean clearance of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Volume of Distribution (Vz/F) [MAD]
Description
Mean volume of distribution of NM26-2198 after single dose administrations in healthy subjects.
Time Frame
Pre-dose on Day 1 through Day 57
Title
Pharmacokinetics of NM26-2198: Volume of Distribution (Vz/F) [MAD]
Description
Mean volume of distribution of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Accumulation Ratio for Cmax (Racc,cmax) [MAD]
Description
Mean accumulation ratio for Cmax of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Pharmacokinetics of NM26-2198: Accumulation Ratio for AUCtau (Racc,AUCtau) [MAD]
Description
Mean accumulation ratio for AUCtau of NM26-2198 after multiple dose administrations in patients with AD.
Time Frame
Pre-dose on Day 1 through Day 85
Title
Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [SAD]
Time Frame
Pre-dose on Day 1 through Day 57
Title
Percentage of subjects developing treatment-emergent anti-drug antibodies (ADAs) [MAD]
Time Frame
Pre-dose on Day 1 through Day 85
Title
Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [SAD]
Time Frame
Pre-dose on Day 1 through Day 57
Title
Percentage of subjects developing treatment-enhanced anti-drug antibodies (ADAs) [MAD]
Time Frame
Pre-dose on Day 1 through Day 85
Title
Mean ADA titers [SAD]
Time Frame
Pre-dose on Day 1 through Day 57
Title
Mean ADA titers [MAD]
Time Frame
Pre-dose on Day 1 through Day 85

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: SAD: Non-Asian ethnicity with grandparents and parents of non-Asian descent or Japanese descent having all four Japanese grandparents born in Japan. SAD: Male or female aged 18 to 55 years; MAD: Male or female ≥18 years of age. Weight of 45 kg to 100 kg and BMI of 18.0 to 30.0 kg/m2. SAD: 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. MAD: Diagnosis of chronic AD. MAD: EASI score ≥16. MAD: vIGA-AD™ score of ≥3. MAD: Atopic lesions cover ≥10% of body surface area (BSA). MAD: PP-NRS score ≥4. MAD: Daily use of non-prescription emollient. Note: Other protocol-defined Inclusion criteria apply. Exclusion Criteria: SAD: 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. Clinically important ECG abnormalities or history/evidence thereof. SAD: Use of prescription or non-prescription medications (except occasional use of paracetamol). MAD: Diagnosis of protocol-specified skin diseases other than AD, or history of other significant skin condition that could interfere with study assessments. MAD: History or ongoing allergy/hypersensitivity or history, or history of hypersensitivity to biological drugs. MAD: Recent receipt of immunoglobulin or blood products. MAD: Recent treatment with protocol-specified investigational treatments, or any prior treatment with dupilumab, tralokinumab, lebrikizumab, nemolizumab, or other protocol-specified drugs. MAD: AD with recent ocular involvement requiring chronic ocular corticosteroid treatment. MAD: Chronic pruritis due to conditions other than AD. MAD: Acute AD superinfection, recent superficial skin infection, or other chronic/acute infection requiring protocol-defined treatments. MAD: Recent use of sedating antihistimines, systemic corticosteroids, cytotoxic treatments, other immunosuppressive/immunomodulating agents, and other protocol-specified prohibited medications. MAD: Recent topical corticosteroid or prescription moisturizer use. Note: Other protocol-defined Exclusion criteria apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Lichtlen, MD, PhD, BBA
Phone
+41-44-533-22-92
Email
clinicaltrials@numab.com
Facility Information:
Facility Name
California Clinical Trials Medical Group (CCTMG) managed by Parexel
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hakop Gevorkyan, MD, MBA

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics and Exploratory Clinical Activity of NM26-2198 in Healthy Subjects and in Patients With Moderate-to-severe Atopic Dermatitis (AD)

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