Study to Evaluate the Efficacy and Safety of ATI-045 in Atopic Dermatitis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aclaris Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Decision date (initial)

2025-09-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Aclaris Therapeutics, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Dose response, Safety, Pharmacodynamic

To evaluate the efficacy of ATI-045 compared to placebo, as measured by the change in Eczema Area and severity index (EASI) score in patients with moderate-to-severe AD

Secondary objectives 2

1. 1. To evaluate the treatment effect of ATI-045 compared to placebo, on additional clinical outcome measures
2. 2. To evaluate the safety and tolerability, including characterization of the immunogenicity profile ATI-045 in patients with moderate-to-severe AD

Conditions and MedDRA coding

Atopic dermatitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Male or female adults aged ≥ 18 and ≤ 70 years, inclusive at the time of consent.
2. 2. Chronic AD that has been present for ≥ 6 months before the screening visit and with no significant AD flares during the past 4 weeks before screening.
3. 3. EASI score ≥ 16 at the screening and the baseline visit (W0D1).
4. 4. vIGA score ≥ 3 (scale of 0 to 4) at the screening and the baseline visit.
5. 5. Minimum weekly average of the daily PP-NRS score ≥ 4 in the 7 days before the baseline visit.
6. 6. ≥10% body surface area (BSA) of AD involvement at the screening and baseline visit.
7. 7. Photographs at screening are representative of the disease diagnosis and extent
8. 8. History of inadequate response to treatment for AD with topical medications; or determination that topical treatments are otherwise medically inadvisable. Note: History of inadequate response to or lack of tolerability (as assessed by the investigator based on information obtained from medical chart, patient’s physician, or directly from the patient), of a stable regimen (≥ 4 weeks or for the duration recommended by the product prescribing information) of one or more topical treatments (e.g., moderate to high potency TCSs and/or TCIs) before the Screening visit, or for whom topical treatments are otherwise inadvisable.
9. 9. The patient has applied a stable dose of non-medicated topical moisturizer (ideally once or twice daily) for ≥ 7 days prior to the baseline visit and agrees to continue using the same moisturizer daily at the same frequency throughout the study.
10. 10. Willing and able to comply with all clinic visits and study-related procedures and questionnaires.
11. 11. Provide signed informed consent.
12. 12. A male patient who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use a condom and a highly effective contraception from screening, throughout the duration of the study treatment and for 180 days after the last dose of study drug.
13. 13. A female patient of childbearing potential who is sexually active with a non-sterilized male partner agrees to routinely use highly effective contraception from screening, throughout the duration of the study treatment and for 120 days after the last dose of study drug.

Exclusion criteria 24

1. 1. Treatment with any of the following: a. Intravenous immunoglobulin within 12 weeks prior to the baseline visit (W0D1) b. Systemic antibiotics within 2 weeks prior to the baseline visit (W0D1) c. Topical antibiotics within 1 week prior the baseline visit (W0D1) d. Topical medicated treatment that could affect atopic dermatitis should be prohibited for at least 2 weeks prior to baseline visit. Example: topical corticosteroids, crisaborole, calcineurin inhibitors, ruxolitinib, roflumilast, tars, antimicrobials, medical devices, and bleach baths. e. Topical products containing urea within 1 week prior to baseline visit (W0D1) f. Doxepin, hydroxyzine, or diphenhydramine within 1 week prior to the baseline visit (W0D1) g. Patient has used systemic treatments (other than biologics) that could affect AD less than 4 weeks or 5 half-lives (whichever is longer) prior to the baseline visit (W0D1), including, but not limited to, retinoids, calcineurin inhibitors, methotrexate, cyclosporine, hydroxycarbamide (hydroxyurea), azathioprine, oral/injectable corticosteroids, baricitinib, upadacitinib, and abrocitinib. h. Biologics for AD treatments (such as dupilumab, tralokinumab, lebrikizumab, investigational biologics) within 5 half- lives or 12 weeks, whichever is longer prior to the baseline visit (W0D1) i. An investigational drug (non-biologic) within 4 weeks or within 5 half-lives (if known), whichever is longer prior to the baseline visit (W0D1) j. Phototherapy and photochemotherapy for AD within 4 weeks prior to the baseline visit (W0D1) k. A live (attenuated) vaccine within 12 weeks prior to the baseline visit (W0D1)
2. 10. Abnormal (clinically significant) electrocardiogram (ECG) at the screening visit. Entry of any patient with an abnormal (not clinically significant) ECG must be approved and documented by signature of the Investigator. In the case of a corrected QT interval (Fridericia) (QTcF) > 450 ms or > 470 ms (patients with bundle branch block) or PR interval outside the range of 115 to 220 ms, assessment may be repeated once for eligibility determination.
3. 11. Positive test result for hepatitis B surface antigen (HbsAg), Hepatitis B core Antibody (HBcAb), antihepatitis C virus (HCV), or for human immunodeficiency virus (HIV), or a known history of HIV infection at the screening visit. Patients with a history of hepatitis B vaccination without a history of hepatitis B are allowed to enroll in the study.
4. 12. Known presence of active tuberculosis or a history of tuberculosis disease. History of tuberculosis exposure/infection (e.g. positive purified protein derivative test or an alternative test like Interferon Gamma Release Assay) is not an exclusion, though history of positive test will require prior documented completed prophylactic treatment. In case of known latent tuberculosis (or prior indeterminate result), or positive/indeterminate result at screening when done, participants will be allowed to participate only after a consultation with a TB specialist or infectious diseases specialist, and their written approval. Note: In North America, this is only based on history – there is no testing or imaging required as part of this exclusion criterion, outside North America QuantiFERON GOLD TB test will also be done at screening.
5. 13. Diagnosed with a helminthic parasitic infection within 6 months prior to the screening visit or at high risk of these infections as per the judgement of the Investigator.
6. 14. Major surgical or major dental procedure within 8 weeks prior to the screening visit or a planned major surgery during the study.
7. 15. Patient is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the study. Female patients must agree to not have egg retrieval from W0D1 until at least 120 days after the last dose of study product.
8. 16. Male patient intends to donate sperm during this study or within 180 days since the last dose of study drug.
9. 17. History of malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease free for at least 5 years prior to the baseline visit.
10. 18. The patient has donated or lost ≥ 450 mL of blood (including plasmapheresis) or had a transfusion of any blood product within 90 days prior to the baseline visit.
11. 19. Poorly controlled hypertension, not suitable for participation in this study in the judgement of the Investigators at screening assessment.
12. 2. History of anaphylaxis following biologic therapy.
13. 20. Patient has excessive sun exposure, is planning a trip in a sunny climate, or has used tanning booths within 4 weeks prior to W0D1, or is not willing to minimize natural and artificial sunlight exposure during the study. Use of sunscreen products and protective apparel are recommended when exposure cannot be avoided
14. 21. The patient plans to use any other prohibited medication or undergo any prohibited procedure during the study.
15. 22. Current or any recent (within last 12 months prior to screening) substance (including alcohol) abuse disorder. Note: Marijuana use is allowed, if not considered substance abuse by the investigator. If a patient uses marijuana, it is recommended that patient refrain from all marijuana use for 24 hours prior to any study site visit.
16. 23.The patient is compulsorily detained for a medical or psychiatric illness.
17. 24.The patient or their immediate family are personnel at the study site.
18. 3. Patient has a known or suspected allergy to any component of the investigational product
19. 5. Other dermatologic conditions that might confound a diagnosis of AD or a treatment assessment as per the Investigator.
20. 6. Uncontrolled chronic disease that might require burst of oral corticosteroids, e.g., comorbid severe uncontrolled asthma or a history of ≥ 2 asthma exacerbations within the last 12 months requiring systemic [oral and/or parenteral] corticosteroid treatment or hospitalization for > 24 hours).
21. 7. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks prior to the baseline visit, or superficial skin infections within 1 week prior to the baseline visit. NOTE: patients may be rescreened after infection resolves.
22. 8. Any clinically significant illness that may affect the safety, increase the risk for seizure or lower the seizure threshold, or potentially confound the study results, as per the Investigator, such as cardiovascular, neurologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, immunologic, endocrine, or psychiatric disease or disorder, or other abnormality. It is the responsibility of the Investigator to assess the clinical significance of a patient’s condition; however, consultation with the Medical Monitor may be warranted.
23. 9. Clinically significant laboratory abnormalities including but not limited to: a.Hemoglobin < 10.0 g/dL b.White blood cell count < 2.5 ×10^9 /L (< 2500/mm3) c.Absolute neutrophil count of < 1.0 × 10^9 /L (< 1000/mm3) d.Absolute lymphocyte count of < 0.5 × 10^9 /L (< 500/mm3) e.Platelet count <100,000/μL f.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values ˃ 2 times the upper limit of normal (ULN) g.Alkaline phosphatase (ALP) > 3 × ULN h.Total bilirubin level > 2 × ULN unless participant has been diagnosed with Gilbert syndrome, and this is clearly documented
24. 4. History of allergy to corticosteroids, diphenhydramine, hydroxyzine, cetirizine, or fexofenadine.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Percent change from baseline in EASI score at Week 24

Secondary endpoints 10

1. 1. Proportion of patients with validated Investigator Global Assessment (vIGA) treatment success (IGA-TS) (defined as score 0/1 and a reduction ≥2 points from baseline), at Week 24
2. 2. Proportion of patients with EASI reduction of 75% (EASI75) relative to baseline score at Week 24
3. 3. Change and percent change from baseline in weekly average of the daily Peak Pruritus Numerical Rating Scale (PP-NRS) score at Week 24
4. 4. Proportion of patients with a 4-point improvement or greater from baseline in weekly average of the daily Peak Pruritus Numerical Rating Scale (PP-NRS) at Week 24
5. 5. Proportion of patients with EASI reduction of 50% (EASI50) relative to baseline score at Week 24
6. 6. Proportion of patients with EASI reduction of 90% (EASI90) relative to baseline score at Week 24
7. 7. Change from baseline in body surface area (BSA) at Week 24
8. 8. Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) after first study drug dose on W0D1 until patient’s last visit.
9. 9. Abnormality of clinical laboratory evaluations, 12-lead ECGs, vital signs
10. 10. Anti-ATI-045 antidrug antibody (ADA)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aclaris Therapeutics Inc.

Sponsor organisation

Aclaris Therapeutics Inc.

Address

701 Lee Road Suite 103

City

Chesterbrook

Postcode

19087-5612

Country

United States

Scientific contact point

Organisation

Aclaris Therapeutics Inc.

Contact name

Aclaris Lead Clinical Development Physician

Public contact point

Organisation

Aclaris Therapeutics Inc.

Contact name

Aclaris Clinical Trial Information Desk

Third parties 6

Locations

3 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications