Safety, Tolerability and Pharmacokinetics of LNK01004 Ointment in Adults With Atopic Dermatitis.

A Phase Ib, Randomized, Double-Blind, Vehicle-Controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LNK01004 Ointment in Adults Patients With Mild to Moderate Atopic Dermatitis.

The purpose of the study is to evaluate the Safety, Tolerability, and Pharmacokinetics of LNK01004 ointment (0.3%, 1.0%, and 1.5%) vs vehicle twice daily (BID) in Adults Patients with Atopic Dermatitis.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: LNK01004 ointment 0.3%; Drug: LNK01004 ointment 1.0%; Drug: LNK01004 ointment 1.5%; Drug: Vehicle BID

Detailed Description

This is a multicenter, randomized, double-blind, vehicle-controlled, dose-escalation study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LNK01004 ointment twice daily (BID) in participants with Mild to Moderate atopic dermatitis as compared with vehicle cream BID.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Nanjing, China
    • Hospital for skin diseases, Institute of Dermatology, Chinese Academy of Medical Sciences.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants were diagnosed with atopic dermatitis (AD) for at least 6 months.
• Participants with an Investigator's Global Assessment (IGA) score of 2 to 3 at screening and baseline.
• Participants with body surface area (BSA) of AD involvement, excluding the scalp, face, and intertriginous areas, of 3% to 20% at screening and baseline.
• BMI of 18.0-30.0 kg/m2, with body weight ≥ 50 kg for man and ≥ 40 kg for woman.
• Be willing to comply with the study lifestyle restraints, e.g., no washing of the administered area within 6 hours of study drug administration, no sweaty exercise.

Exclusion Criteria:

• Participants with a physical condition which, in the Investigator´s opinion, might interfere with the assessment of atopic dermatitis or expose the patient to an unacceptable risk by study participation.
• Participants with current evidence of any acute skin infection with a history of recurrent or chronic severe skin infection.
• Participants with known allergies to components or excipients of the test drug.
• Participants who are pregnant, nursing, or planning a pregnancy during the study period.
• Systemic immunosuppressive or immunomodulating drugs (eg, oral or injectable corticosteroids, mycophenolate mofetil, PDE4 inhibitor) used for atopic dermatitis within 4 weeks or 5 half-lives of baseline (whichever is longer).
• Participants with the following hematologic abnormities at screening:
• Leukocytes < 3.0 × 10^9/L.
• Neutrophils < lower limit of normal.
• Hemoglobin < 10 g/dL.
• Lymphocytes < 0.8 × 10^9/L
• Platelets < 100 × 10^9/L.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 × upper limit of normal.
• TBiL ≥ 1.5 × ULN, or ULN < TBiL < 1.5 × ULN but judged by the investigator to be abnormal clinically significant;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LNK01004 ointment 0.3%; Participants will receive LNK01004 ointment 0.3% twice daily	Drug: LNK01004 ointment 0.3%; LNK01004 ointment 0.3% for topical application
Experimental: LNK01004 ointment 1.0%; Participants will receive LNK01004 ointment 1.0% twice daily	Drug: LNK01004 ointment 1.0%; LNK01004 ointment 1.0% for topical application
Experimental: LNK01004 ointment 1.5%; Participants will receive LNK01004 ointment 1.5% twice daily	Drug: LNK01004 ointment 1.5%; LNK01004 ointment 1.5% for topical application
Experimental: Vehicle; Participants will receive vehicle BID	Drug: Vehicle BID; Inactive vehicle matched to LNK01004 ointment for topical application.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Events (TEAE)	Number of participants with at least one TEAE.	Baseline up to week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving a 75% Decrease From Baseline in EASI Score (EASI-75)	The number of participants with a decrease of at least 75% from the baseline EASI total score is presented. The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease), with positive results indicating an increase from baseline in EASI total score (i.e., increased symptoms) and negative results indicating a decrease from baseline score (i.e., decreased symptoms). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI.	Baseline and Weeks 1, 2, and 4
Number of Participants Achieving ≥4-Point Improvement in WI-NRS Pruritus Score	The number of participants achieving a ≥4-point improvement from Baseline in WI-NRS score is presented. The WI-NRS is a simple, single item scale to assess the subject-reported severity of this symptom, on a scale ranging from 0 ("no itch") to 10 ("worst imaginable itch") the subject experienced in the previous 24 hours. Higher scores indicate greater symptom severity.	Baseline and Weeks 1, 2, and 4
Maximum concentration (Cmax) for LNK01004 in plasma	Cmax is defined as the maximum observed plasma concentration for LNK01004	Day1 and Day 7
Area under plasma concentration versus time curve, time zero to infinity	The area under the plasma concentration-time curve is a method of measurement of the total exposure of a drug in plasma	Day 1 and Day7
Mean Percentage Change From Baseline in Eczema Area and Severity Index (EASI) Score	The EASI is an instrument to measure the severity and extent of AD. The body is first divided into 4 areas: head (10% of skin), arms (20%), trunk (30%), and legs (40%). Then, the area affected is scored from 0 (0% involvement) to 6 (90-100% involvement), and severity is scored from 0 ('none') to 3 ('severe'). The EASI combines the area affected and severity ratings to get a final composite score ranging from 0 (no disease) to 72 (maximal disease). Note that palms and soles were treated as appropriate but were not counted towards any measurements of EASI.	Baseline and Weeks 1, 2, and 4
Percentage of Participants Achieving an Investigator's Global Assessment (IGA) Score of 0 to 1 Who Have an Improvement of ≥ 2 Points From Baseline	IGA is an assessment scale used to determine severity of atopic dermatitis (AD) and clinical response to treatment on a 5-point scale (0 = clear; 1 = almost clear; 2 = mild; 3 = moderate; 4 = severe) based on erythema and papulation/infiltration. Therapeutic response was an IGA score of 0 (clear) or 1 (almost clear). An IGA responder was defined as a participant achieving an IGA score of 0 to 1 and an IGA score improvement at least 2 from baseline.	Baseline and Weeks 1, 2, and 4

Collaborators and Investigators

• Sponsor: Lynk Pharmaceuticals Co., Ltd
• Investigators: Principal Investigator: Qianjin Lu, Hospital for skin diseases, Institute of Dermatology, Chinese Academy of Medical Sciences.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2023
• Primary Completion (Actual): June 18, 2024
• Study Completion (Actual): June 18, 2024

Study Registration Dates

• First Submitted: August 10, 2024
• First Submitted That Met QC Criteria: August 11, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2024
• Last Update Submitted That Met QC Criteria: August 11, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: LK004102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No