A Study to Investigate Efficacy, Safety and Tolerability of Barzolvolimab Versus Placebo in Adults With Cold Induced Urticaria and Symptomatic Dermographism Inadequately Controlled by H1-antihistamines (EMBARQ - ColdU and SD)

This study is looking for adults, aged 18 or older, who have been diagnosed with either cold urticaria or symptomatic dermographism for at least three months. To be considered, your hives (for cold urticaria) or itchy welts (for symptomatic dermographism) should still be bothering you, even if you're regularly taking an antihistamine.

Specifically, for cold urticaria, your skin should react strongly to cold, and for symptomatic dermographism, light scratching should cause a noticeable reaction and itch. It's also important that your blood tests are normal, and you're willing to track your symptoms daily and attend all study appointments. You might have tried other 'biologic' treatments before, or you might not have – both are generally acceptable.

However, some people won't be able to join. This includes pregnant or breastfeeding women, or those who have another clear reason for their chronic hives besides cold or scratching. Also, if you have other active itchy skin conditions, certain serious medical conditions, HIV, hepatitis B or C, or have recently had a live vaccine, you won't be able to participate. You must also agree to use effective contraception if you could become pregnant or father a child.

If you decide to take part in this study, you'll first have a screening period that could last up to four weeks. During this time, the study team will carry out health checks and tests to make sure the study is right for you. They will confirm your diagnosis of cold urticaria or symptomatic dermographism with specific tests, like a 'TempTest' for cold reactions or a 'FricTest' for scratching reactions, and check your overall health.

After screening, the study is divided into different periods. For the first 24 weeks, you'll be randomly chosen to receive either the study drug, barzolvolimab (as an injection), or a placebo (a dummy injection with no active drug). You won't know which one you're getting, nor will your study doctor. If you receive barzolvolimab during this period, you'll get a higher dose at the beginning, followed by smaller doses every four weeks. After these 24 weeks, for the next 28 weeks, all participants will receive barzolvolimab every eight weeks. Finally, there's a 16-week follow-up period where you won't receive any study medication but will be observed to see how you're doing.

Throughout the entire study, which lasts about a year and a half, you'll need to attend regular clinic visits and keep a daily record of your symptoms using an electronic diary. The study team will monitor your health closely, perform examinations, and take blood samples to check your progress and look for any side effects.