EP262 for Chronic Hives

(CALM-CSU Trial)

No longer recruiting at 51 trial locations

Overseen By Danielle Petersel

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Escient Pharmaceuticals, Inc

Must be taking: H1 antihistamines

Disqualifiers: Chronic inducible urticaria, atopic dermatitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EP262 for individuals with chronic hives, a condition causing ongoing, itchy welts on the skin. The goal is to determine the effectiveness of EP262 in reducing hive symptoms compared to a placebo (a pill with no active medicine). Participants will receive one of three doses of EP262 or a placebo. The trial seeks individuals whose chronic hives have not improved with standard antihistamine treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of H1 antihistamine, so you will not have to stop taking this medication.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that EP262 has promising safety results from earlier studies. In past trials, most participants tolerated the treatment well, with some experiencing side effects, though these were not serious. EP262 has undergone human testing before, indicating it is reasonably safe. So far, trial data suggest that EP262 is a safe option for managing chronic hives. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for chronic hives, which typically include antihistamines and corticosteroids, EP262 works by targeting a different mechanism in the immune response. Researchers are excited because EP262 is designed to specifically modulate immune pathways that traditional treatments don't address. This approach has the potential to offer relief for those who don't respond well to existing medications, possibly leading to more effective and longer-lasting control of hives.

What evidence suggests that EP262 might be an effective treatment for chronic hives?

Earlier research found EP262 to be safe and well-tolerated at different doses. It blocks a part of the immune system that activates certain cells, potentially reducing symptoms of chronic hives. Studies with similar treatments have shown significant symptom improvement, suggesting EP262 could be effective. Although complete data on EP262 is still being gathered, these early results are promising for people with chronic spontaneous urticaria (chronic hives). ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for people with chronic spontaneous urticaria (CSU), also known as hives, who still have symptoms despite taking up to four times the normal dose of H1 antihistamines. Participants must have a documented history of CSU and a UAS7 score of 16 or higher.

Inclusion Criteria

I am taking a stable dose of an H1 antihistamine, up to four times the normal amount.

I have chronic hives with a UAS7 score of 16 or more, despite taking antihistamines.

Exclusion Criteria

I have a skin condition that causes long-term itching.

You have hives with a known cause other than chronic spontaneous urticaria.

You have hives that are caused by a specific trigger.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive EP262 or placebo for chronic spontaneous urticaria

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EP262
• Placebo

Trial Overview The study is testing EP262, an oral medication, against a placebo to see if it can help with CSU. It's conducted across multiple centers where participants are randomly assigned to receive either EP262 or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: EP262 50 mg Experimental Treatment 1 Intervention

Group II: EP262 25 mg Experimental Treatment 1 Intervention

Group III: EP262 150 mg Experimental Treatment 1 Intervention

Group IV: Placebo Placebo Group 1 Intervention

EP262 is already approved in United States for the following indications:

Approved in United States as EP262 for:

• None approved yet; under investigation for chronic spontaneous urticaria, chronic inducible urticaria, and atopic dermatitis

Who Is Running the Clinical Trial?

Escient Pharmaceuticals, Inc

Lead Sponsor

Trials

6

Recruited

340+

Published Research Related to This Trial

In a study of 31 patients with chronic urticaria, loratadine (10 mg daily for 28 days) significantly reduced symptoms like erythema, wheals, and prurigo in 71% of patients, compared to no improvement in the placebo group.

The treatment also led to a marked reduction in skin reactions to histamine, indicating loratadine's efficacy in managing chronic urticaria symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of treatment with loratadine in patients with chronic urticaria]. Siergiejko, Z., Chyrek-Borowska, S.[2015]

In a real-life clinical analysis of 51 chronic urticaria patients, omalizumab demonstrated high efficacy, achieving complete remission in 83% of patients with chronic spontaneous urticaria (CSU) and 70% with chronic inducible urticaria (CindU).

Omalizumab was found to be safe, with rapid symptom relief occurring within the first week for 57% of CSU patients, and the treatment's effectiveness was not influenced by baseline IgE levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: a retrospective clinical analysis. Metz, M., Ohanyan, T., Church, MK., et al.[2022]

A double-blind placebo-controlled trial involving 20 patients showed that enzyme-potentiated desensitization (EPD) significantly reduced allergy symptoms related to Parietaria and grass pollen compared to placebo, indicating its clinical efficacy in treating pollinosis.

EPD treatment led to beneficial immunological changes, such as an increase in T-CD8+ cells and a decrease in specific IgE levels, suggesting that EPD may enhance the body's tolerance to allergens with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of enzyme-potentiated desensitization in the treatment of pollinosis: a double-blind placebo-controlled trial. Astarita, C., Scala, G., Sproviero, S., et al.[2013]

In a study involving 20 patients with chronic idiopathic urticaria, both doses of BW 825C (4 mg and 8 mg) were found to be highly effective in controlling symptoms compared to placebo.

The treatment was well-tolerated, with few adverse reactions reported, and no significant increase in drowsiness or other side effects compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An assessment of the novel antihistamine BW 825C in the treatment of chronic idiopathic urticaria. A placebo-controlled study. Gibson, JR., Harvey, SG., Barth, JH., et al.[2019]

In a study of 360 patients with perennial allergic rhinitis, a 0.125% cetirizine nasal spray significantly improved symptoms compared to placebo, with a clinically meaningful difference in the percentage of days with no or mild symptoms (30.8% vs. 16.7%, P = 0.011).

The safety profile was similar across all treatment groups, with no significant differences in adverse events, indicating that the 0.125% concentration is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-ranging, placebo-controlled study of cetirizine nasal spray in adults with perennial allergic rhinitis. Clement, P., Roovers, MH., Francillon, C., et al.[2019]

Enzyme-potentiated desensitization (EPD) is a promising new method for treating otolaryngic allergies, showing effectiveness in a preliminary study involving 36 patients since February 1997.

EPD addresses various allergic conditions, including allergic rhinitis and asthma, and offers advantages over traditional allergy treatments, suggesting it could be a valuable alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme-potentiated desensitization in otolaryngic allergy. Pulec, JL.[2006]

A single dose of EPD immunotherapy administered 6-8 weeks before the pollen season significantly reduced the need for oral antihistamines in patients with seasonal rhinitis, indicating its efficacy in managing allergy symptoms.

While EPD did not show a significant improvement in rhinoconjunctivitis scores compared to placebo, the overall safety profile was good, suggesting it may be effective for short-term prevention of seasonal allergy symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventive symptomatic immunotherapy versus placebo in seasonal rhinitis due to grasses in children and to Parietaria in adult patients. Troise, C., Bignardi, D., Modena, P., et al.[2006]

A systematic review of 23 clinical trials involving 2480 participants from 22 countries found a significant increase in the number of new pharmacological treatments, particularly biologics, for H1-antihistamine-refractory chronic spontaneous urticaria (CSU).

The review highlighted disparities in trial representation, with underrepresentation of minority groups and populations from lower-income countries, and noted that less than half of the trials reported patient perspectives, indicating a need for improved trial design and standardized outcome reporting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence Gaps in Clinical Trials of Pharmacologic Treatment for H1-Antihistamine-Refractory Chronic Spontaneous Urticaria: A Systematic Review and Future Perspectives. Nochaiwong, S., Chuamanochan, M., Ruengorn, C., et al.[2022]

Citations

1. escientpharma.com escientpharma.com/escient-pharmaceuticals-announces-positive-results-from-phase-1-study-of-ep262-a-first-in-class-oral-mrgprx2-antagonist-for-mast-cell-mediated-disorders/

Press Releases EP262 was safe and well-tolerated at all doses tested, at exposures several fold above doses required for efficacy in preclinical disease ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06077773

Study Details | NCT06077773 | Phase 2, Multicenter, ... Documented history of chronic spontaneous urticaria (CSU) with a UAS7 greater than or equal to 16 despite stable treatment with H1 antihistamine consistent with ...

3. annallergy.org annallergy.org/article/S1081-1206(24)00343-0/fulltext

The future of targeted therapy in chronic spontaneous ... A meta-analysis found that the rate of response in patients with CSU who responded to updosing was 63.2%. Therefore, approximately 40% of ...

4. withpower.com withpower.com/trial/phase-2-urticaria-9-2023-f6cbb

EP262 for Chronic Hives (CALM-CSU Trial) The study on the antihistamine BW 825C showed it was highly effective in controlling symptoms of chronic urticaria (hives) compared to a placebo.

5. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)00852-3/fulltext

Chronic urticaria: unmet needs, emerging drugs, and new ... Results of this study revealed dose-dependent improvements in UAS7 at week 8 for participants administered 150 mg fenebrutinib daily (least ...

6. escientpharma.com escientpharma.com/escient-pharmaceuticals-initiates-clinical-proof-of-concept-study-of-ep262-a-first-in-class-oral-mrgprx2-antagonist-in-chronic-spontaneous-urticaria/

Press Releases Efficacy and safety of EP262 to be assessed in a randomized, placebo-controlled study in ~90 patients; Second of three clinical ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11946961/

Update on the Treatment of Chronic Spontaneous Urticaria Pooled safety data from study A and B were consistent between dupilumab and placebo with treatment-emergent adverse events (TEAE) of 57.3 ...