Dose Escalation Trial Of Safety, Pharmacokinetic/Pharmacodynamic And Preliminary Clinical Activity of Briquilimab In Adult Patients With Chronic Spontaneous Urticaria (CSU)

Chronic Spontaneous Urticaria Clinical Trial

— BEACON  

Official title:

A Phase 1B/2A, Dose Escalation Trial of Safety, Pharmacokinetic/Pharmacodynamic And Preliminary Clinical Activity of Briquilimab In Adult Patients With Chronic Spontaneous Urticaria (CSU) Who Remain Symptomatic Despite Treatment With, Or Who Cannot Tolerate Omalizumab

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06162728
• Other study ID #: JSP-CP-011
• Secondary ID: 2023-505446-25
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 29, 2023
• Est. completion date: August 30, 2025

Study information

• Verified date: May 2024
• Source: Jasper Therapeutics, Inc.
• Contact: Edwin Tucker, MD
• Phone: 6505491400
• Email: etucker[@]jaspertherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial will be performed as a three-part dose escalating clinical trial where Parts 1 is open label and Parts 2 and 3 are randomized, double-blinded, and placebo-controlled.

The trial is intended to determine the safety and tolerability and assess the preliminary efficacy of briquilimab in adult participants with chronic spontaneous urticaria (CSU), who remain symptomatic despite treatment with H1 antihistamines and omalizumab. Additionally, pharmacokinetic (PK) properties of briquilimab, and other pharmacodynamic (PD) parameters (such as effects on mast cells (MC), serum tryptase levels, and on allergic skin reactivity) will be investigated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: August 30, 2025
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent after the nature of the trial has been fully explained and before performing any trial related assessments

2. Males and females, =18 years old

3. Diagnosis of symptomatic CSU despite treatment as defined by:

1. Diagnosis of CSU for = 6 months

2. 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)

3. 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)

4. 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)

4. 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

5. Blood counts at Screening with:

1. Hemoglobin: = 11 g/dl

2. Platelets: = 100,000/mm3

3. Leucocytes: = 3,000/mm3

4. Neutrophils: = 2,000/mm3

6. Willing and able to complete a daily diary for the duration of the trial and adhere to the trial visit schedule

Exclusion Criteria:

1. Women who are pregnant or nursing or intend to become pregnant during the course of the trial

2. 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

3. 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)

4. 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.)

5. History of anaphylaxis

6. Any H2 antihistamine, leukotriene receptor antagonist or tricyclic antidepressant use within 3 days prior to Screening

7. 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

8. 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

9. Electrocardiogram (ECG) findings at Screening that are considered clinically significant

10. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 x Upper limit of normal (ULN) at Screening

11. Serum total bilirubin >1.5 x ULN, unless attributable to Gilbert's syndrome

12. Estimated creatinine clearance (eCrCl) by Cockcroft-Gault equation using total body weight < 60 mL/min

13. Known HIV+, active hepatitis B or hepatitis C infection, or acute/long-COVID

14. Major abdominal or thoracic surgery within 8 weeks prior to Screening or planned surgery during trial participation

15. 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, Section 8.2) 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.

16. Female participants of childbearing potential not willing to use highly effective contraceptive methods (Section 8.2) during the trial and for at least 150 days after last IP dosing. Women of nonchildbearing 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).

17. Participation in another research trial involving the use of an IP within the last 30 days (or 5 halflives of IP, whichever is longer) prior to Screening

18. 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

19. 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

20. Participants not willing to abstain from blood donations while being on the trial (until EOT Visit)

21. 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

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• Briquilimab
Subcutaneous Administration

Other:
• Placebo
Placebo Comparator

Locations

Country	Name	City	State
Germany	Site 201	Berlin
Germany	Site 203	Bonn
Germany	Site 211	Buxtehude
Germany	Site 209	Dresden
Germany	Site 206	Lübeck
Germany	Site 210	München
Germany	Site 204	Münster
United States	Site 125	Baton Rouge	Louisiana
United States	Site 118	Birmingham	Alabama
United States	Site 109	Boise	Idaho
United States	Site 104	Chevy Chase	Maryland
United States	Site 103	Cincinnati	Ohio
United States	Site 112	Dallas	Texas
United States	Site 117	Fremont	California
United States	Site 110	Indianapolis	Indiana
United States	Site 123	Lafayette	Louisiana
United States	Little Rock Allergy & Asthma Clinical Research Center	Little Rock	Arkansas
United States	Site 113	Miami	Florida
United States	Site 111	Murray	Utah
United States	Site 102	North Charleston	South Carolina
United States	Site 122	Overland Park	Kansas
United States	Site 114	Philadelphia	Pennsylvania
United States	Site 107	Saint Louis	Missouri
United States	Site 105	San Diego	California
United States	Site 124	Springfield	Illinois
United States	Site 121	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Jasper Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the safety and tolerability of briquilimab	Incidence and severity of treatment emergent AEs/SAEs	From signing the informed consent form (ICF) through end of trial (EOT) visit (up to 48 weeks)
Secondary	Evaluate the preliminary efficacy of briquilimab-- UAS7 Score	UAS7 is the sum of the daily Hives Severity Score (HSS) and the daily Itch Severity Score (ISS) for seven consecutive days. The possible range of the weekly UAS7 score is 0 - 42.	Change from baseline to Week 12 and all assessment time points through Week 48
Secondary	Evaluate the preliminary efficacy of briquilimab - Urticaria Control Test (UCT)	The UCT score is derived by adding up the scores from each of the four questions. A total score from 0 (no control) to 16 points (complete control) is derived, with a score of = 12 indicating well-controlled disease.	Change from baseline to Week 12 and all assessment time points through Week 48
Secondary	Maximum serum concentration (Cmax)	Maximum serum concentration (Cmax) following a single dose of briquilimab.	Up to 12 weeks
Secondary	Time of maximum serum concentration (Tmax)	Time of maximum serum concentration (Tmax) following a single dose of briquilimab	Up to 12 weeks
Secondary	Minimum plasma concentration (Cmin)	Minimum serum concentration (Cmin) following a single dose of briquilimab	Up to 12 weeks
Secondary	Area under the time-concentration curve from time zero to the last quantifiable concentration (AUClast)	Area under the time-concentration curve from time zero to the last quantifiable concentration (AUClast) following a single dose of briquilimab	Up to 12 weeks