A Multi-center, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of Subcutaneously Delivered ASLAN004 in Adults With Moderate-Severe Atopic Dermatitis
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|ClinicalTrials.gov Identifier: NCT04090229|
Recruitment Status : Active, not recruiting
First Posted : September 16, 2019
Last Update Posted : July 29, 2021
|Condition or disease||Intervention/treatment||Phase|
|Atopic Dermatitis||Drug: ASLAN004 Drug: ASLAN004 Placebo||Phase 1|
The study is designed as a MAD escalation in up to 3 cohorts of patients, followed by a cohort expansion to further confirm the safety and tolerability of the selected dose, prior to further investigation in Phase 2 studies. The cohort expansion will also support the assessment of the trial's secondary efficacy objectives. Approximately 50 patients are planned to be enrolled across the entire study.
Approximately 24 patients are planned to be enrolled in the initial MAD escalation, with a maximum of 3 ascending dose levels (low, medium and high) of ASLAN004 (Cohorts 1-3). In all dose cohorts, 8 patients will be randomized in a 3:1 ratio to receive ASLAN004 (at specified cohort dose, n=6) or matching placebo (n=2). Additional cohorts may be optional depending on the data from the preceding cohort.
An expansion cohort (Cohort 4) of approximately 27 patients is planned and will be randomized in a 2:1 ratio to receive ASLAN004 (n=18) or matching placebo (n=9). The rationale for this is to provide greater assurance about the safety and tolerability of the selected dose level, and to provide preliminary estimates of the PD and clinical effects at this dose, prior to further dose and schedule finding work in Phase 2 studies.
A total of 8 subcutaneous injections of ASLAN004 or matching placebo will be administered according to a weekly schedule of injection from Day 1 (baseline visit) to Day 50 (Week 7) of the study. Patients will be closely monitored and observed for a period of 30 minutes after each injection of study drug (all visits). The clinical assessments and blood sampling for safety laboratory tests, PK analysis, ADA assays, and biomarkers will be performed at each visit as noted in the Schedule of Assessments. The treatment period will end at the last day of Week 8 (ie., Day 56) after which patients will be followed every week for 12 weeks for safety, PK parameters, ADA, and PD marker assessments. In the event that patients develop adverse events (AEs)/serious AEs (SAEs) which are determined as definitely related, probably related, or possibly related to ADA, and/or patients have a positive ADA result, additional unscheduled sampling of ADA may be performed during the study or after Day 141, as deemed clinically necessary. The exact timepoints for ADA sampling after Day 141 will be discussed between the Investigator and Sponsor for each case.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||52 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Double Blind, Placebo-controlled, Randomized|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Multi-center, Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of Subcutaneously Delivered ASLAN004 in Adults With Moderate-Severe Atopic Dermatitis|
|Actual Study Start Date :||September 9, 2019|
|Estimated Primary Completion Date :||August 30, 2021|
|Estimated Study Completion Date :||November 30, 2021|
Subcutaneous injections of ASLAN004 100 mg/mL will be administered into the thigh or abdomen, except for the 2 inches (5 cm) around the navel.
|Placebo Comparator: ASLAN004 Placebo||
Drug: ASLAN004 Placebo
Subcutaneous injections of ASLAN004 Placebo will be administered into the thigh or abdomen, except for the 2 inches (5 cm) around the navel.
- To assess the safety and tolerability of multiple ascending doses of ASLAN004: Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Baseline to 12 weeks safety follow up ]Incidence of treatment-emergent adverse events (TEAEs) reported from the administration of study drug on Day 1 until the completion of the study.
- Percentage change from baseline in Eczema Area and Severity Index (EASI) score weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]
- Proportion of patients with 50%, 75%, and 90% improvement in the EASI score (EASI50, EASI75, and EASI90) weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]
- Percentage change from baseline in the Pruritus Numerical Rating Scale (NRS) score weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]
- Proportion of patients with at least a 4-point improvement in the Pruritus NRS score weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]
- Proportion of patients who achieve an Investigator Global Assessment (IGA) score of 0 or 1 weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]
- Percentage change from baseline in the Patient-Oriented Eczema Measure (POEM) weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]
- Percentage change from baseline in percent body surface area (%BSA) affected weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]
- PK parameters throughout the dosing period, and serum concentrations by scheduled timepoints. [ Time Frame: Baseline to 12 weeks safety follow up ]Measurement of area under the curve (AUC) at Week 8 (AUC0-last), maximum observed concentration (Cmax) at Week 1, time to Cmax (tmax) at Week 1, Ctrough throughout the dosing period, and serum concentrations by scheduled timepoints.
- Change from baseline in PD markers of allergic inflammation (TARC and total IgE) weekly up to Week 8. [ Time Frame: Baseline up to Week 8 ]Measurement of absolute values of TARC and total IgE in serum concentration and percentage of change
- Measurement of ASLAN004 Anti-Drug Antibody over time. [ Time Frame: Baseline to 12 weeks safety follow up ]Measurement of ADA levels in serum
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04090229
|United States, California|
|Center for Dermatology Clinical Research, INC|
|Fremont, California, United States, 94538|
|First OC Dermatology|
|Los Angeles, California, United States, 92708|
|United States, Florida|
|Direct Helpers Research Center|
|Miami, Florida, United States, 33012|
|United States, Pennsylvania|
|Paddington Testing Co, INC|
|Philadelphia, Pennsylvania, United States, 19103|
|United States, Texas|
|Dermatology Treatment and Research Cancer|
|Dallas, Texas, United States, 75230|
|Australia, New South Wales|
|Premier Specialists Pty Ltd|
|Kogarah, New South Wales, Australia, 2217|
|Veracity Clinical Research Pty Ltd|
|Woolloongabba, Queensland, Australia, 4102|
|Skin Health Institute, Inc.|
|Carlton, Victoria, Australia, 3053|
|Australia, Western Australia|
|Fremantle, Western Australia, Australia, 6160|
|National Skin Centre|
|Singapore, Singapore, 308205|
|Changi General Hospital|
|Singapore, Singapore, 529889|