Evaluation of Briquilimab Safety and Pharmacokinetics in Adults with Chronic Spontaneous Urticaria Unresponsive to H1 Antihistamines or Omalizumab
- Trial ID
- 2023-505446-25-00
- Protocol
- JSP-CP-011
- Sponsor
- Jasper Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and tolerability of briquilimab in adult patients with **Chronic Spontaneous Urticaria** (CSU) who remain symptomatic despite treatment with H1 antihistamines and/or omalizumab, or who cannot tolerate omalizumab. Assessing safety and tolerability is crucial for determining the potential of briquilimab as a therapeutic option for this patient population, ensuring that the treatment does not pose undue risk and is well-tolerated by patients.
Secondary objectives include:
- Evaluating the preliminary efficacy of briquilimab, which will provide initial insights into its potential therapeutic benefits in reducing symptoms of CSU.
- Assessing the pharmacokinetic (PK) and pharmacodynamic (PD) profile of briquilimab, which is essential for understanding the drug's absorption, distribution, metabolism, and excretion, as well as its biological effects and mechanism of action.
Participants
The clinical trial involves a total of **42 participants** diagnosed with **Chronic Spontaneous Urticaria** (CSU). The study population includes both **male and female** subjects aged **18 years and above**. Participants were selected based on their diagnosis of symptomatic CSU despite treatment, with specific criteria including a history of CSU for at least six months and the presence of itch and hives for eight consecutive weeks prior to screening. The trial does not include a vulnerable population. Participants are required to have stable blood counts and must be willing to maintain a consistent dose of H1-antihistamines throughout the trial. Additionally, they must be capable of completing a daily diary and adhering to the trial visit schedule. The selection process ensures that participants have a consistent health status, allowing for a focused evaluation of the safety and tolerability of briquilimab.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, and **controlled** study to evaluate the safety, pharmacokinetics, and preliminary clinical activity of **briquilimab** in adult patients with **chronic spontaneous urticaria** (CSU) who remain symptomatic despite treatment with H1 antihistamines and/or omalizumab, or who cannot tolerate omalizumab. The trial is structured in a **Phase 1b/2a** dose escalation format. The estimated duration of the trial is from January 8, 2024, to May 31, 2026.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as a diagnosis of CSU for at least six months and the presence of itch and hives for eight consecutive weeks despite treatment. Following the screening, participants will be randomized to receive either briquilimab or a placebo via **subcutaneous injection**. The trial includes multiple follow-up visits to monitor the incidence and severity of treatment-emergent adverse events (AEs) and serious adverse events (SAEs), as well as laboratory assessments, electrocardiograms (ECGs), and vital signs. The primary endpoint focuses on the safety profile, while secondary endpoints include the Urticaria Activity Score over seven days (UAS7), Hive Severity Score (HSS7), and Itch Severity Score (ISS7).
The expected length of participant involvement is approximately 12 weeks, during which they are required to maintain a stable dose of H1-antihistamines and complete a daily diary. Conditions that may lead to early termination from the study include non-compliance with the trial protocol, withdrawal of consent, or the occurrence of significant adverse events. The end-of-study visit will assess the overall response to the treatment and collect final data on the primary and secondary endpoints.
Treatment
The clinical trial involves the administration of **Briquilimab**, an experimental medication, to evaluate its safety and tolerability in adult patients with Chronic Spontaneous Urticaria (CSU). Briquilimab is provided in the form of an **injection** and is administered via **subcutaneous injection**. The dosing schedule and frequency of administration are determined based on the study protocol, which aims to assess the pharmacokinetic and pharmacodynamic properties of the drug. Briquilimab is a protein-based therapeutic developed by Jasper Therapeutics Inc., and its administration is closely monitored to ensure participant compliance and safety.
In addition to Briquilimab, a **placebo** is utilized in the study to serve as a comparator treatment. The placebo consists of a solution containing 10 mM sodium acetate, 9.0% (w/v) sucrose, and 0.02% (w/v) polysorbate 20, with a pH of 5.2. The placebo is designed to mimic the appearance and administration route of Briquilimab, ensuring blinding in the trial. The placebo does not contain any active pharmaceutical ingredients and is used to evaluate the efficacy of Briquilimab against a non-active control.
**Epinephrine**, also known as adrenaline tartrate, is included in the trial as an auxiliary medication. It is provided in the form of an auto-injector, specifically the EpiPen, which is a prefilled disposable device. Epinephrine is administered via **intramuscular injection** and is used as a cardiac stimulant and catecholamine. Its inclusion in the trial is to manage any potential acute allergic reactions that may occur during the administration of Briquilimab or the placebo. The use of epinephrine is a standard precautionary measure in clinical trials involving new therapeutic agents.
Efficacy
The efficacy of Briquilimab in the treatment of **Chronic Spontaneous Urticaria (CSU)** will be assessed using several secondary endpoints. These include the Urticaria Activity Score over 7 days (UAS7), Hive Severity Score over 7 days (HSS7), and Itch Severity Score over 7 days (ISS7). Additionally, the Urticaria Control Test (UCT) will be utilized to evaluate the control of urticaria symptoms. The complete response rate will be determined by the proportion of participants who are urticaria-free, indicated by a UAS7 score of 0. The well-controlled rate will be assessed by the proportion of participants with a UAS7 score of ≤6 or a UCT score of ≥12. Time to complete response or well-controlled disease, as well as time to relapse, will also be measured. Furthermore, serum pharmacokinetic (PK) concentrations of Briquilimab over time will be analyzed, including parameters such as Cmax, Cmin, and AUC as appropriate.
Inclusion and Exclusion Criteria
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 and above
- i. For Cohorts 1, 2, 3, 4a, 4b, 5, 5b, 6 and 7:Diagnosis of symptomatic CSU despite treatment as defined by: a) Diagnosis of CSU for ≥ 6 months; b) The presence of itch and hives for ≥ 8 consecutive weeks at any time prior to Screening despite current use of H1-antihistamines (as reported by the participant); c) The presence of itch and hives for ≥ 8 consecutive weeks at any time prior to Screening despite treatment with omalizumab or intolerance to omalizumab (as reported by the participant); d) UAS7 of ≥ 16 and ISS7 of ≥ 8 on Days –10 through Day –3 of Screening (not more than 2 missing entries during that period, re-screening may be considered with Medical Monitor approval)ii. For Cohorts 8 and 9: Diagnosis of symptomatic CSU despite treatment as defined by: a. Diagnosis of CSU for ≥ 6 months (as per local and international guidance)b. The presence of itch and hives for ≥ 8 consecutive weeks at any time prior to Screening despite current use of H1-antihistamines (as reported by the participant) c. Participants may be omalizumab naïve or have been previously exposed to omalizumab independent of treatment duration or response, and require an 8-week washout period prior to the first dose of IP. The 8-week washout is not required for participants who are refractory to omalizumab. Note: Omalizumab-refractory participants are defined as those treated with standard doses of omalizumab (i.e., 300 mg omalizumab every 4 weeks) for at least 3 consecutive months and who had no improvement in CSU, and remained symptomatic resulting in omalizumab discontinuation, as confirmed by investigator assessment. d. UAS7 of ≥ 16 and ISS7 of ≥ 8 on 7 consecutive days between Day -10 through Day -1 of Screening (not more than 2 missing entries during that period, re-screening may be considered with Medical Monitor approval)
- Use of H1-antihistamines on stable dose up to four-fold of the approved dose since Screening and not expected to change during first 12 weeks of the trial
- Blood counts at Screening with: a) Hemoglobin: ≥ 11 g/dl; b) Platelets: ≥ 100,000/mm3; c) Leucocytes: ≥ 3,000/mm3; d) Neutrophils: ≥ 2,000/mm3
- Willing and able to complete a daily diary for the duration of the trial and adhere to the trial visit schedule
Exclusion Criteria
- Women who are pregnant or nursing or intend to become pregnant during the course of the trial
- Dominant comorbid chronic urticaria with a clearly defined predominant or sole trigger (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact urticaria
- 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 anaphylaxis
- Any H2 antihistamine, leukotriene receptor antagonist or tricyclic antidepressant use within 3 days prior to Screening
- Experimental monoclonal antibody therapy (e.g., dupilumab, ligelizumab, etc.) within 6 months or Janus kinase (JAK) inhibitors within 5 half-lives prior to first IP dosing
- 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 first IP dosing
- 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+, active hepatitis B or 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 last IP dosing. 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 an 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 the 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 (until EOT Visit)
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 08 Jan 2024 | 31 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Briquilimab | Test | INJECTION | SUBCUTANEOUS INJECTION | — | — | PRD10460835 |
Placebo (10 mM sodium acetate, 9.0% (w/v) sucrose, 0.02% (w/v) polysorbate 20, pH 5.2) | Placebo | N/A | — | — | — | N/A |
EPINEPHRINE | Other | PHF00231MIG | INTRAMUSCULAR INJECTION | — | — | SCP16873011 |