A Phase 3 Study of Barzolvolimab in Patients with Chronic Spontaneous Urticaria (EMBARQ – CSU1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celldex 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]

Trial duration

4 Apr 2025 → ongoing

Decision date (initial)

2024-11-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celldex Therapeutics, Inc.

External identifiers

EU CT number

2024-513210-36-00

WHO UTN

U1111-1309-7747

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Efficacy, Pharmacokinetic, Others

To evaluate the clinical effect of barzolvolimab, compared to placebo, in reducing urticaria
activity as assessed by weekly urticaria activity score (UAS7) at Week 12

Secondary objectives 6

1. • To evaluate the clinical effect of barzolvolimab, compared to placebo, in reducing urticaria activity as assessed by weekly itch severity score (ISS7) and weekly hive severity score (HSS7) and additional UAS7-based efficacy measures at Week 12
2. • To evaluate the clinical effect of barzolvolimab in reducing angioedema as assessed by weekly angioedema activity score (AAS7) at Week 12 for participants with AAS7 > 0 at baseline
3. • To evaluate the clinical effect of barzolvolimab, compared to placebo, in reducing urticaria activity in participants refractory to omalizumab treatment at Week 12
4. • To evaluate the clinical effect of barzolvolimab in reducing urticaria activity at Weeks 4 and 24 (vs placebo) and at Weeks 52 and 68, and assessing clinically meaningful benefits in urticaria activity over time
5. • To evaluate the clinical effect of barzolvolimab in reducing urticaria activity in participants refractory to omalizumab treatment at Weeks 4 and 24 (vs placebo) and at Week 52
6. • To evaluate the clinical effect of barzolvolimab on the health-related quality of life at Weeks 12, 24, and 52

Conditions and MedDRA coding

Chronic Spontaneous Urticaria

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Read, understood, and provided written informed consent, and Health Insurance Portability and Accountability Act (HIPAA) authorization if applicable, after the nature of the study has been fully explained. Participants must be able to provide informed consent themselves.
2. 2. Male or female, ≥ 18 years of age at the time of signing the informed consent.
3. 3. CSU ≥ 6 months prior to Screening. Note: the investigator should establish the presence of CSU for the noted duration based on all available supporting documentation, including written medical records and communication with the participants’ previous healthcare providers, if applicable.
4. CSU refractory to a stable dose and regimen containing a second-generation H1AH as defined by all of the following: • Recurrent pruritic wheals with or without angioedema for ≥ 6 weeks at any time prior to Screening (Visit 1) despite treatment with a H1AH (hives consistent with CSU should be documented and confirmed by the investigator prior to randomization) • Participants must have been on a stable dose and regimen containing a secondgeneration H1 antihistamine (H1AH) at approved or increased (up to 4x approved) dose as background therapy for the treatment of CSU for ≥ 4 weeks prior to randomization and which is expected to remain stable throughout the study. • UAS7 (range: 0 to 42) ≥ 16 and ISS7 (range: 0 to 21) ≥ 8 during the 7-day period (Day -7 to Day -1) immediately prior to randomization.
5. 5. Willing and able to comply with all study requirements and procedures, including the completion of a daily symptom diary during screening and throughout the study.

Exclusion criteria 4

1. 1. Diseases with possible symptoms of urticaria or angioedema such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), autoimmune syndromes with urticarial lesions (e.g., Schnitzler Syndrome) and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency).
2. 2. Chronic urticaria whose predominant manifestation is due to CIndU including symptomatic dermographism [urticaria factitia], cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact urticaria Note: CIndU is not excluded per se
3. 3. Any other active pruritic skin diseases that would confound CSU assessments (e.g., atopic dermatitis, psoriasis, bullous pemphigoid, dermatitis herpetiformis, prurigo nodularis, chronic pruritus of unknown origin) based on the investigator's clinical judgment.
4. 4. Prior receipt of barzolvolimab or other anti-KIT therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change from baseline in UAS7 at Week 12

Secondary endpoints 6

1. 1. Mean change from baseline in ISS7 and HSS7 at Week 12
2. 2. Proportion of participants with UAS7 = 0 at Week 12
3. 3. Proportion of participants with UAS7 ≤ 6 at Week 12
4. 4. Proportion of participants with AAS7 = 0 at Week 12 in participants who have AAS7 > 0 at baseline
5. 5. Mean change from baseline in UAS7 in participants refractory to omalizumab treatment at Week 12
6. 6. Proportion of participants with UAS7 = 0 in participants refractory to omalizumab treatment at Week 12

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celldex Therapeutics Inc.

Sponsor organisation

Celldex Therapeutics Inc.

Address

53 Frontage Road Suite 220

City

Hampton

Postcode

08827-4034

Country

United States

Scientific contact point

Organisation

Celldex Therapeutics Inc.

Contact name

Science Department

Public contact point

Organisation

Celldex Therapeutics Inc.

Contact name

Clinical Development

Third parties 14

Locations

10 EU/EEA countries · 89 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 224 files

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

Application history

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