An Outpatient, Randomized, Double-Blinded, Placebo-Controlled, Cross-Over Study of the Efficacy of ARS-2 in Patients with Chronic Spontaneous Urticaria

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ars Pharmaceuticals IRL Limited

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

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

Decision date (initial)

2025-08-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ARS Pharmaceuticals IRL Ltd.

External identifiers

EU CT number

2025-521930-27-00

ClinicalTrials.gov

NCT06927999

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine the effect of ARS-2 (0.5 mg or 1 mg) versus placebo on itch and hive

Secondary objectives 4

1. To assess time to effect and duration of effect versus placebo on itch and hive
2. To assess time to effect and duration of effect versus steroid (Period 0) on itch and hive
3. To assess the effect on angioedema
4. To assess the safety and tolerability of ARS-2-Adverse events (AEs)

Conditions and MedDRA coding

Chronic Spontaneous Urticaria (CSU)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Is a male or female between the ages of 18 and 65 years, inclusive.
2. Has been clinically diagnosed with CSU and experiences an acute flare of moderate to severe urticaria symptoms (itch and hive severity UAS score ≥ 2) approximately 1-2 times a month or every other month consistently during the past year while on a chronic treatment. Enrolled subjects will record UAS daily for urticaria and VAS daily for angioedema during the screening period, which will serve as baseline.
3. Has been on a daily chronic treatment for ≥ 6 weeks.
4. Is willing to use a smartphone study application to record study assessments and AEs.
5. Has no medical history of clinically significant hypertension and cardiovascular disease in the last 10 years. Controlled hypertension without beta blocker confirmed by the Investigator is acceptable.
6. At screening, has stable vital signs in the following ranges (after 5 minutes of rest): • Systolic blood pressure (SBP) ≥90 and ≤140 milliliters of mercury (mmHg) • Diastolic blood pressure (DBP) ≥50 and ≤90 mmHg • Heart rate (HR) ≥45 and ≤100 beats per minute (bpm) Note: Each blood pressure (BP) should be taken after at least 5 minutes rest in a chair with back supported, legs uncrossed, and upper arm bared (slight recline for comfort ispermitted). If vital signs are out of range, the Investigator may obtain two additional readings, so that up to 3 consecutive assessments are made within 1 hour.
7. If female, is not pregnant or breastfeeding based on a negative urine pregnancy test at baseline and each clinical site visit.
8. Is able to communicate clearly with the Investigator and staff; able to read, complete questionnaires, and perform study procedures on the smartphone study application.
9. Is willing and able to provide written informed consent prior to participating in the study

Exclusion criteria 7

1. 1. Has a history of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results.
2. 2. Has any clinically significant medical condition or physical exam (PE) finding as deemed inappropriate by the Investigator
3. 3. Has abnormal cardiovascular exam at screening including any prior history of myocardial infarction or clinically significant abnormal electrocardiogram (ECG) (e.g., second- or third-degree heart block, uncontrolled arrhythmia, QTcF [Fridericia’s correction] interval >450 msec for male subjects and >470 msec for female subjects).
4. 4. Has had significant traumatic injury or major surgery within 30 days prior to study screening
5. 5. Known hypersensitivity to any compound in the test product, or any other closely related compound (e.g., dihydropyridine-derived molecules).
6. 6. Has participated in a clinical trial within 30 days prior to the first dose of study drug. Participation in an observational (non-interventional) study is not excluded as long as there are no scheduling conflicts with this study
7. 7. Has an immediate family member of the Investigator, or an employee of the study center, with direct involvement in the proposed study, or other studies under the direction of the Investigator or study center or is in a dependent relationship with a study center employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling), or may consent under duress.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Change in itch score (Uniform Assessment System [UAS] as compared to placebo at each timepoint on exacerbation days • Change in hive score (UAS) as compared to placebo at each timepoint on exacerbation days

Secondary endpoints 4

1. • Time to a 1-point decrease in itch and hive scores (UAS) • Time to a 2-point decrease in itch and hive scores (UAS) • Time to resolution • Time to recurrence within 24 hours
2. • Time to a 1-point decrease in itch and hive scores (UAS) • Time to a 2-point decrease in itch and hive scores (UAS) • Time to resolution • Time to recurrence within 24 hours
3. • Time to return to resolution by patient-rated visual analog scale (VAS) • Time to recurrence of symptoms within 24 hours • Change in pain (VAS) • Change in size of angioedema based on photographs
4. • Adverse events (AEs)

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ars Pharmaceuticals IRL Limited

Sponsor organisation

Ars Pharmaceuticals IRL Limited

Address

The Black Church, Saint Marys Place North Saint Marys Place North

City

Dublin 7

Postcode

D07 P4AX

Country

Ireland

Scientific contact point

Organisation

Ars Pharmaceuticals IRL Limited

Contact name

Osnat

Public contact point

Organisation

Ars Pharmaceuticals IRL Limited

Contact name

Osnat

Locations

1 EU/EEA country · 1 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 31 files

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

Application history

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