Clinical trial NCT06162728: Dose Escalation Trial of Safety, Pharmacokinetic/Pharmacodynamic and Preliminary Clinical Activity of Briquilimab in Adult Patients with Chronic Spontaneous Urticaria (CSU)
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 H1 Antihistamines And/or Omalizumab, or Who Cannot Tolerate Omalizumab
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Spontaneous Urticaria
Keywords: Urticaria
Skin Diseases, Vascular
Skin Diseases
Immune System Diseases
Chronic Urticaria
Pathologic Processes
Chronic Disease
Itch
Hives
Wheals
Lead sponsor: Jasper Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1: Cohorts 1 and 2, 3+3 dose escalation design

Cohorts 1 through 9 will be enrolled sequentially in a dose escalating fashion starting from the lowest dose proposed.

The Treatment Period in Part 2 (Cohorts 3, 4, 5, 8, and 9) and Part 3 (Cohort 6 and 7) will be performed in a double-blind, placebo-controlled manner.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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. i. For Cohorts 1, 2, 3, 4a, 4b, 5, 5b, 6 and 7: 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 7 consecutive days between Day -10 through Day-1 of Screening

   ii. For Cohorts 8 and 9: Diagnosis of symptomatic CSU despite treatment as defined by:
   1. Diagnosis of CSU for ≥ 6 months (as per local and international guidance)
   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. Participants may be omalizumab naïve or have been previously exposed to omalizumab independent of treatment duration or response
   4. UAS7 of ≥ 16 and ISS7 of ≥ 8 on 7 consecutive days between Day -10 through Day -1 of Screening
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

Primary outcomes:
measure: Evaluate the safety and tolerability of briquilimab
timeFrame: From signing the informed consent form (ICF) through end of trial (EOT) visit (up to 48 weeks)
Secondary outcomes:
measure: Evaluate the preliminary efficacy of briquilimab-- UAS7 Score
timeFrame: Change from baseline to Week 12 and all assessment time points through Week 48
measure: Evaluate the preliminary efficacy of briquilimab - Urticaria Control Test (UCT)
timeFrame: Change from baseline to Week 12 and all assessment time points through Week 48
measure: Maximum serum concentration (Cmax)
timeFrame: Up to 12 weeks
measure: Time of maximum serum concentration (Tmax)
timeFrame: Up to 12 weeks
measure: Minimum plasma concentration (Cmin)
timeFrame: Up to 12 weeks
measure: Area under the time-concentration curve from time zero to the last quantifiable concentration (AUClast)
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Site 118
state: Alabama
city: Little Rock
country: United States
facility: Little Rock Allergy & Asthma Clinical Research Center
state: Arkansas
city: Fremont
country: United States
facility: Site 117
state: California
city: San Diego
country: United States
facility: Site 105
state: California
city: Miami
country: United States
facility: Site 113
state: Florida
city: Tampa
country: United States
facility: Site 116
state: Florida
city: Boise
country: United States
facility: Site 109
state: Idaho
city: Springfield
country: United States
facility: Site 124
state: Illinois
city: Indianapolis
country: United States
facility: Site 110
state: Indiana
city: Overland Park
country: United States
facility: Site 122
state: Kansas
city: Baton Rouge
country: United States
facility: Site 125
state: Louisiana
city: Lafayette
country: United States
facility: Site 123
state: Louisiana
city: Baltimore
country: United States
facility: Site 101
state: Maryland
city: Chevy Chase
country: United States
facility: Site 104
state: Maryland
city: White Marsh
country: United States
facility: Site 121
state: Maryland
city: Saint Louis
country: United States
facility: Site 107
state: Missouri
city: Cincinnati
country: United States
facility: Site 103
state: Ohio
city: Philadelphia
country: United States
facility: Site 114
state: Pennsylvania
city: N Charleston
country: United States
facility: Site 102
state: South Carolina
city: Dallas
country: United States
facility: Site 112
state: Texas
city: Murray
country: United States
facility: Site 111
state: Utah
city: Seattle
country: United States
facility: Site 115
state: Washington
city: Berlin
country: Germany
facility: Site 201
city: Bonn
country: Germany
facility: Site 203
city: Buxtehude
country: Germany
facility: Site 211
city: Dresden
country: Germany
facility: Site 209
city: Frankfurt
country: Germany
facility: Site 208
city: Hannover
country: Germany
facility: Site 207
city: Lübeck
country: Germany
facility: Site 206
city: Marburg
country: Germany
facility: Site 202
city: München
country: Germany
facility: Site 210
city: Münster
country: Germany
facility: Site 204
Study officials:
affiliation: Jasper Therapeutics
name: Medical Director
role: STUDY_DIRECTOR
References: