Phase 2b Study of ASLAN004 in Adults With Moderate-to-Severe Atopic Dermatitis

• ClinicalTrials.gov Identifier: NCT05158023
• Recruitment Status: Completed
• First Posted: December 15, 2021
• Last Update Posted: April 26, 2024
• Sponsor: ASLAN Pharmaceuticals
• Information provided by (Responsible Party): ASLAN Pharmaceuticals

Tracking Information

• First Submitted Date: December 2, 2021
• First Posted Date: December 15, 2021
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: March 16, 2022
• Actual Primary Completion Date: June 13, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 20, 2022)

Percent change from Baseline in Eczema Area and Severity Index (EASI) at Week 16 [ Time Frame: Baseline, Week 16 ]

The EASI score is used to measure the severity and extent of AD and measured erythema, infiltration, excoriation and lichenification on 4 anatomic regions of the body: head, trunk, upper and lower extremities. The total EASI score ranges from 0 (minimum) to 72 (maximum) points, with the higher scores reflecting the worse severity of AD

• Original Primary Outcome Measures (submitted: December 2, 2021): Percent change from Baseline in Eczema Area and Severity Index (EASI) [ Time Frame: Week 16 ]

Current Secondary Outcome Measures (submitted: January 20, 2022)

• Proportion of patients achieving validated Investigator's Global Assessment (vIGA) response of 0 (clear) or 1 (almost clear) at Week 16 [ Time Frame: Week 16 ]
  IGA is an assessment scale used to determine severity of 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 is an IGA score of 0 (clear) or 1 (almost clear).
• Proportion of patients with EASI 50, 75 and 90 at Week 16 [ Time Frame: Week 16 ]
  EASI scores range from 0 to 72 (severe)The EASI responder is defined as a participant who achieves a ≥50% improvement (EASI 50), ≥75% improvement (EASI 75), or ≥90% improvement (EASI 90) from baseline in the EASI score.
• Proportion of patients with EASI <7 at Week 16 [ Time Frame: Week 16 ]
  EASI scores range from 0 to 72 (severe)
• Percent Change in EASI score from Baseline over time [ Time Frame: Baseline, Week 16 ]
  EASI scores range from 0 to 72 (severe)
• Absolute and percent change in Pruritus Numerical Rating Scale (P-NRS) over time [ Time Frame: Baseline, Week 16 ]
  The P-NRS is an 11-point scale used by patients to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating the worst itch imaginable. Pruritus assessments will be recorded daily by the patient using an electronic diary
• Proportion of patients achieving a 4-point reduction in P-NRS [ Time Frame: Baseline, Week 16 ]
  The P-NRS is an 11-point scale used by patients to assess their worst itch severity over the past 24 hours, with 0 indicating no itch and 10 indicating the worst itch imaginable. Pruritus assessments will be recorded daily by the patient using an electronic diary.
• Change in Body Surface Area (BSA) affected with AD [ Time Frame: Baseline, Week 16 ]
  BSA ranges from 0% to 100 % with higher values representing greater extent of AD.
• Change in SCORing Atopic Dermatitis (SCORAD) from Baseline to Week 16 [ Time Frame: Baseline, Week 16 ]
  The SCORAD is a validated measure of the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with higher values indicating a more extensive and/or severe condition.
• Change in Dermatology Life Quality Index (DLQI) from Baseline to Week 16 [ Time Frame: Baseline, Week 16 ]
  The DLQI is a 10-item, validated questionnaire used in clinical practice and clinical trials to assess the patient's perception of the impact of AD disease symptoms and treatment on their quality of life (QoL). The 10 questions assess QoL over the past week, with an overall scoring of 0 (absent disease) to 30 (severe disease). A high score is indicative of a poor QoL.
• Change in Patient-Oriented Eczema Measure (POEM) from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]
  The POEM is a 7-item questionnaire that assesses disease symptoms (dryness, itching, flaking, cracking, sleep loss, bleeding and weeping) with a scoring system of 0 (absent disease) to 28 (severe disease) (high score indicative of poor quality of life [QOL])
• Change in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Index Score United States and United Kingdom Algorithm from Baseline to Week 16 [ Time Frame: Baseline, Week 16 ]
  The EQ-5D-5L is a 2-part measurement. The second part is assessed using a VAS that ranges from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine
• Change in Hospital Anxiety Depression Scale (HADS) from Baseline to Week 16 [ Time Frame: Baseline to Week 16 ]
  HADS is a 14-item scale. Seven of the items relate to anxiety and seven items relate to depression. Each item on the questionnaire is scored from 0 (minimum score) - 3 (maximum score) and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. The total HADS score or subscores may be regarded as a global measure of psychological distress; higher scores indicate greater levels of anxiety or depression.
• Absolute and percent change in sleep disturbance SD-NRS over time [ Time Frame: Baseline to Week 16 ]
  The SD-NRS is an 11-point scale used by patients to assess their sleep disturbance severity over the past 24 hours, with 0 indicating no or minimal sleep disturbance and 10 indicating the worst imaginable sleep disturbance. SD-NRS assessments will be recorded daily by the patient using an electronic diary.
• Proportion of patients achieving a 4-point reduction in SD-NRS from Baseline to at Week 16 [ Time Frame: Baseline to Week 16 ]
• Number of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) from study drug administration (Day 1) to Week 28 [ Time Frame: : Baseline to Week 28 ]
  TEAEs are defined as AEs that develop or worsen or become serious during on-treatment period (time from the first dose of study drug until Week 28. A TESAE is defined as any untoward medical occurrence that results in any of the following outcomes: death, life-threatening, requires initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or is considered as medically important event. Any TEAE includes participants with both serious and non-serious AEs.

Original Secondary Outcome Measures (submitted: December 2, 2021)

• Proportion of patients achieving validated Investigator's Global Assessment (vIGA) response of 0 or 1 [5 point scale] [ Time Frame: Week 16 ]
• Proportion of patients with EASI 50, 75 and 90 [ Time Frame: Week 16 ]
• Proportion of patients with EASI <7 [ Time Frame: Week 16 ]
• Percent Change in EASI score from Baseline over time [ Time Frame: Week 16 ]
• Absolute and percent change in Pruritus Numerical Rating Scale (P-NRS) over time [ Time Frame: Week 16 ]
• Proportion of patients achieving a 4-point reduction in P-NRS [ Time Frame: Week 16 ]
• Change in Body Surface Area (BSA) affected with AD [ Time Frame: Week 16 ]
• Change in Patient Reported Outcomes (PROs) over time [ Time Frame: Baseline to Week 16 ]
• Absolute and percent change in sleep NRS over time [ Time Frame: Baseline to Week 16 ]
• Number of Treatment-Emergent Adverse Event and Treatment-Emergent Serious Adverse Event [ Time Frame: Baseline to Week 16 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 2b Study of ASLAN004 in Adults With Moderate-to-Severe Atopic Dermatitis
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging Trial to Evaluate the Efficacy and Safety of ASLAN004 in Adult Patients With Moderate-to-Severe Atopic Dermatitis
• Brief Summary: Phase 2b study designed to evaluate the efficacy and safety of ASLAN004 in adult patients with moderate-to-severe Atopic Dermatitis (AD) who are candidates for systemic therapy. This study will have 5 treatment arms (4 active and 1 placebo).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Atopic Dermatitis

Intervention

• Drug: Placebo Comparator
  Sterile solution for subcutaneous injection
• Biological: ASLAN004
  Sterile solution for subcutaneous injection

Study Arms

• Placebo Comparator: Placebo every two weeks q2w
  Placebo q2w - placebo loading dose equivalents at Baseline and Week 1, then placebo dose equivalents every 2 weeks (q2w) from Week 2 to Week 14.
  Intervention: Drug: Placebo Comparator
• Experimental: ASLAN004 300 mg q2w
  ASLAN004 300 mg q2w - loading doses at Baseline and Week 1, followed by regular doses of 300mg q2w from Week 2 to Week 14.
  Intervention: Biological: ASLAN004
• Experimental: ASLAN004 400 mg q2w
  ASLAN004 400 mg q2w - loading doses at Baseline, Week 1 and Week 2, followed by regular doses of 400 mg ASLAN004, alternating with placebo dose equivalents, q2W from Week 4 to Week 14.
  Intervention: Biological: ASLAN004
• Experimental: ASLAN004 400 mg every four weeks q4w
  ASLAN004 400 mg q4w - loading doses at Baseline, Week 1 and Week 2, followed by regular doses of 400 mg or alternating placebo (q2W) to Week 14.
  Intervention: Biological: ASLAN004
• Experimental: ASLAN004 600 mg q4w
  ASLAN004 600 mg q4w - loading doses at Baseline, Week 1 and Week 2, followed by regular doses of 600 mg ASLAN004, alternating with placebo dose equivalents, q2W from Week 4 to Week 14.
  Intervention: Biological: ASLAN004

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 20, 2023): 302
• Original Estimated Enrollment (submitted: December 2, 2021): 295
• Actual Study Completion Date: September 5, 2023
• Actual Primary Completion Date: June 13, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female patients with a clinical diagnosis of AD for at least 1 year;
2. vIGA score of ≥3 at Screening and Baseline;
3. ≥10% BSA of AD involvement at Screening and Baseline;
4. EASI score ≥16 at Screening and Baseline;
5. History of inadequate response to treatment with topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI);
6. Twice daily application of a consistent amount of topical emollient for at least 7 days prior to randomization.

Exclusion Criteria:

1. Immunosuppressive/immunomodulating drugs, systemic therapies or phototherapy within 4 weeks prior to randomization;
2. Treatment with leukotriene inhibitors within 4 weeks prior to randomization;
3. Treatment with topical therapies (including TCS, TCI, topical phosphodiesterase inhibitors, topical JAK inhibitors) or prescription moisturizers, within 1 week prior to randomization;

4. Previous treatment at any time prior to randomization with monoclonal antibody / biologic therapeutic agents as follows;

   1. Prior exposure to dupilumab (Dupixent®) which was discontinued due to lack of efficacy, loss of response, or adverse event;
   2. Investigational or approved agents targeting interleukins IL-4 or IL-13 ligands or receptors of IL-4 or IL-13, including but not limited to lebrikizumab, tralokinumab or ASLAN004;
   3. Other investigational or approved biologic drug within 16 weeks or within 5 half-lives (if known), whichever is longer, prior to the Baseline visit;
   4. Cell-depleting biologics, including, but not limited to, rituximab within 6 months prior to the Baseline visit;
5. Inadequate organ function, abnormal lab result, uncontrolled blood pressure or other health condition considered clinically significant by the investigator at the Screening visit;
6. History of HIV, Hepatitis B, Hepatitis C or active/latent Tuberculosis infection;
7. History of immunosuppression including history of invasive opportunistic infections;
8. Treatment with live attenuated vaccine within 8 weeks prior to randomization;
9. Parasitic infection within 4 weeks prior to baseline travel within 3 months prior to randomization to areas of high parasitic exposure;
10. Have skin comorbidities that in the opinion of the Investigator may interfere with study assessments;
11. Pregnant or breastfeeding women;
12. Patients unwilling to use adequate birth control.
13. Active COVID infection at baseline.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Dominican Republic, India, New Zealand, Poland, Singapore, United States

Administrative Information

• NCT Number: NCT05158023
• Other Study ID Numbers: ASLAN004-003
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ASLAN Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: ASLAN Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Chief Medical Officer; ASLAN Pharmaceuticals

• PRS Account: ASLAN Pharmaceuticals
• Verification Date: April 2024