Evaluation of Briquilimab and Adrenaline Tartrate in Chronic Inducible Urticaria Unresponsive to H1-Antihistamines in Adults

Trial ID: 2023-507534-24-00
Protocol: JSP-CP-010
Sponsor: Jasper Therapeutics Inc.

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Diseases & Conditions

Urticaria chronic

Objectives

The primary objective of this study is to evaluate the **safety** and tolerability of a single dose of briquilimab in patients with Cold Urticaria (ColdU) or Symptomatic Dermographism (SD) who remain symptomatic despite the use of H1 antihistamines. This is clinically relevant as it aims to determine the potential of briquilimab as a therapeutic option for patients with these forms of **Chronic Inducible Urticaria**, who have limited treatment options and continue to experience symptoms despite standard therapy.

Secondary objectives include:

Evaluating the preliminary efficacy of briquilimab.
Assessing the pharmacokinetic (PK) profile of briquilimab.

Participants

The clinical trial involves **participants** diagnosed with **Chronic Inducible Urticaria**, specifically those with Cold Urticaria (ColdU) or Symptomatic Dermographism (SD), who continue to experience symptoms despite the use of H1 antihistamines. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a stable health status, as indicated by specific blood count criteria, and must have been using H1-antihistamines at a stable dose up to four times the approved dose for at least four weeks prior to the screening visit. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include a positive cold stimulation test for ColdU participants and a positive FricTests® for SD participants during screening. Participants are expected to adhere to the trial visit schedule and maintain their current lifestyle, including diet and physical activity, throughout the study period.

Plans and Procedures

The clinical trial is designed as a **randomized**, double-blind, controlled study to evaluate the safety and tolerability of a single dose of **briquilimab** in patients with **Chronic Inducible Urticaria** (CIndU) who remain symptomatic despite treatment with H1-antihistamines. The trial will commence with a dose escalation phase to determine the optimal dosing regimen. The study is expected to start recruitment on January 8, 2024, and conclude by December 22, 2025. Participants will be involved in the study for a duration that includes multiple visits, starting with an inclusion (screening) visit, followed by several follow-up visits, and concluding with an end-of-study visit.

The inclusion visit will involve obtaining written informed consent and confirming eligibility based on criteria such as age (≥18 years), diagnosis of Cold Urticaria (ColdU) or Symptomatic Dermographism (SD), and stable use of H1-antihistamines. Follow-up visits will be scheduled to monitor the incidence and severity of treatment-emergent adverse events (AEs/SAEs), conduct laboratory assessments, and evaluate vital signs. Secondary endpoints will include provocation testing, urticaria control tests, and pharmacokinetic assessments of briquilimab. The end-of-study visit will assess the overall response to treatment and any long-term effects.

Participants are expected to adhere to the trial visit schedule, and their involvement may be terminated early if they experience severe adverse reactions, fail to comply with the study protocol, or withdraw consent. The trial aims to provide valuable insights into the management of CIndU and the potential role of briquilimab in improving patient outcomes.

Treatment

The clinical trial involves the administration of **Briquilimab**, an investigational medication, to evaluate its safety and tolerability in adult patients with Chronic Inducible Urticaria who remain symptomatic despite treatment with H1-antihistamines. **Briquilimab** is provided in the form of an injection and is administered via **subcutaneous injection**. The active substance in Briquilimab is a protein classified under "Protein - Other," and it is not a pediatric formulation. The trial aims to assess the effects of a single dose of Briquilimab, with the pharmaceutical form being an injection. The sponsor of this investigational product is Jasper Therapeutics Inc.

In addition to Briquilimab, the trial utilizes **Epinephrine** as an auxiliary treatment. Epinephrine, also known as **Adrenaline Tartrate Ph. Eur.**, is a cardiac stimulant and catecholamine. It is administered via **intramuscular injection** using a device known as EpiPen, which has a CE mark. The pharmaceutical form of Epinephrine is denoted as PHF00231MIG. This medication is included in the trial to manage potential acute allergic reactions, ensuring participant safety. The administration of Epinephrine is not part of the experimental treatment but serves as a standard-of-care therapy in emergency situations.

Efficacy

The efficacy of Briquilimab in the clinical trial will be assessed using several primary and secondary endpoints. Primary endpoints include the incidence and severity of treatment-emergent adverse events (AEs) and serious adverse events (SAEs), as well as laboratory assessments, electrocardiograms (ECG), and vital signs. Additionally, specific assessments for expected adverse events such as taste change and hair color change will be conducted.

Secondary endpoints focus on the clinical activity of Briquilimab in patients with **Chronic Inducible Urticaria**. These include provocation testing to determine the critical temperature threshold (CCT) for Cold Urticaria (ColdU) and the critical friction threshold (CFT) for Symptomatic Dermographism (SD). The Urticaria Control Test (UCT) will be utilized to evaluate the complete response rate, defined as the proportion of participants who are urticaria-free with a UCT score of 16, and the well-controlled rate, defined as a UCT score of 12 or higher. Additional measures include the time to complete response or well-controlled disease, time to relapse, and serum pharmacokinetic (PK) concentration of Briquilimab over time, with modelled PK parameters such as Cmax, Cmin, and AUC being analyzed as appropriate.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Written informed consent after the nature of the trial has been fully explained and before performing any trial related assessments
Males and females, ≥18 years old
Diagnosis of ColdU or SD despite the use of H1-antihistamines as defined by all of the following: Diagnosis of ColdU or SD for ≥ 3 months, symptoms must comprise both wheal and itch or painful sensation; Presence of itch and hives for ≥ 6 consecutive weeks at any time prior to Screening despite current use of H1-antihistamines (as reported by the participant); ColdU participants must have a positive cold stimulation test above 4ºC using TempTests® (wheal and itch or painful sensation) on site during Screening using TempTest® to be eligible; SD participants must have a positive FricTests® with ≥ 3 pins (wheal and itch) on site during Screening to be eligible.
Use of H1-antihistamines on stable dose up to four-fold of the approved dose for at least 4 weeks prior to the Screening visit and not expected to change during first 12 weeks of the trial
Participants with chronic spontaneous urticaria (CSU) are eligible if they present with symptoms consistent with ColdU or SD and ColdU or SD is the dominant type of chronic urticaria
Blood counts at Screening with: Hemoglobin: ≥ 11 g/dl; Platelets: ≥ 100,000/mm3; Leucocytes: ≥ 3,000/mm3; Neutrophils: ≥ 2,000/mm3
Willing and able to participate and adhere to the trial visit schedule

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Exclusion Criteria

Women who are pregnant or nursing or intend to become pregnant during the course of the trial.
Participants who weigh less than 40 kg or more than 125 kg at Screening.
Dominant comorbid chronic urticaria with a clearly defined predominant or sole trigger (chronic inducible urticaria) other than ColdU or SD, including, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact urticaria as well as variants of cold induced urticaria or familial cold autoimmune syndrome, except CSU (see inclusion criterion #5)
Other active diseases with possible symptoms of urticaria, wheals or angioedema, including urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency).
Any other active skin disease associated with chronic itching that might confound the trial evaluations and results in the opinion of the Investigator (e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).
History of severe anaphylaxis as defined by Sampson et al. within 5 years of Screening
Any H2 antihistamine, leukotriene receptor antagonist or tricyclic antidepressant use within 3 days prior to Screening
Therapeutic or experimental monoclonal antibody therapy (e.g., omalizumab, dupilumab, ligelizumab, etc.) within 6 months or Janus kinase (JAK) inhibitors or experimental Bruton Tyrosine Kinase (BTK) inhibitors within 5 half-lives prior to injection of IP.
Immunosuppressive therapy (e.g., systemic corticosteroids, cyclosporine, methotrexate, dapsone, cyclophosphamide, tacrolimus and mycophenolate mofetil, hydroxychloroquine, etc.) within 4 weeks (or 5 half-lives, whichever is longer) prior to injection of IP.
Electrocardiogram (ECG) findings at Screening that are considered clinically significant.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 x Upper limit of normal (ULN) at Screening
Serum total bilirubin >1.5 x ULN, unless attributable to Gilbert’s syndrome.
Estimated creatinine clearance (eCrCl) by Cockcroft-Gault equation using total body weight < 60 mL/min.
Known HIV, hepatitis B, hepatitis C infection, or acute/long-COVID.
Major abdominal or thoracic surgery within 8 weeks prior to Screening or planned surgery during trial participation
Male participants (who are not vasectomized) who are not willing to use highly effective contraceptive methods (when having sexual intercourse with a female partner of childbearing potential and who are not willing to abstain from sperm donation during the trial and for at least 150 days after last IP dosing. A male participant is considered vasectomized if he had a vasectomy at least 4 months prior to Screening and if he has received post-surgical medical assessment of the surgical success of the vasectomy.
Female participants of childbearing potential not willing to use highly effective contraceptive methods during the trial and for at least 150 days after IP dosing in case of early withdrawal). Women of non-childbearing potential, must be surgically sterile (i.e., had undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or be in menopausal state (at least 1 year without menses).
Participation in another research trial involving the use of IP within the last 30 days (or 5 half-lives of IP, whichever is longer) prior to Screening.
Any known contraindications or hypersensitivity to any component of IP, drugs of similar chemical classes (i.e., to murine, chimeric or human antibodies) or antihistamines or leukotrienes.
Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or IP administration or could interfere with the interpretation of trial results and, in the judgment of the Investigator, would make the participant inappropriate for entry into the trial
Participants not willing to abstain from blood donations while being on the trial (Screening to EOT).
Close affiliation with the Investigator (e.g., a close relative, financially dependent on the trial site) or participant who is an employee of the Sponsor’s company.