A Phase 1b/2a, Dose Escalation Trial of Safety, Pharmacokinetic/Pharmacodynamic and Preliminary Clinical Activity of Briquilimab in Adult Patients with Chronic Inducible Urticaria (CIndU) Who Remain Symptomatic Despite Treatment with H1-Antihistamines

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Jasper Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Mar 2024 → 1 Aug 2025

Decision date (initial)

2023-12-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Jasper Therapeutics Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Pharmacodynamic

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.

Secondary objectives 2

1. Evaluate the preliminary efficacy of briquilimab
2. Evaluate the pharmacokinetic (PK) profile of briquilimab

Conditions and MedDRA coding

Chronic Inducible Urticaria

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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 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.
4. 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
5. 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
6. Blood counts at Screening with: Hemoglobin: ≥ 11 g/dl; Platelets: ≥ 100,000/mm3; Leucocytes: ≥ 3,000/mm3; Neutrophils: ≥ 2,000/mm3
7. Willing and able to participate and adhere to the trial visit schedule

Exclusion criteria 22

1. Women who are pregnant or nursing or intend to become pregnant during the course of the trial.
2. Participants who weigh less than 40 kg or more than 125 kg at Screening.
3. 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)
4. 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).
5. 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.).
6. History of severe anaphylaxis as defined by Sampson et al. within 5 years of Screening
7. Any H2 antihistamine, leukotriene receptor antagonist or tricyclic antidepressant use within 3 days prior to Screening
8. 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.
9. 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.
10. Electrocardiogram (ECG) findings at Screening that are considered clinically significant.
11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 x Upper limit of normal (ULN) at Screening
12. Serum total bilirubin >1.5 x ULN, unless attributable to Gilbert’s syndrome.
13. Estimated creatinine clearance (eCrCl) by Cockcroft-Gault equation using total body weight < 60 mL/min.
14. Known HIV, hepatitis B, hepatitis C infection, or acute/long-COVID.
15. Major abdominal or thoracic surgery within 8 weeks prior to Screening or planned surgery during trial participation
16. 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.
17. 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).
18. 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.
19. 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.
20. 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
21. Participants not willing to abstain from blood donations while being on the trial (Screening to EOT).
22. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Incidence and severity of treatment emergent AEs/SAEs
2. Laboratory assessments, ECG, vital signs
3. Supervision of expected AEs: Taste change assessments Hair color change assessment

Secondary endpoints 7

1. Provocation testing: ColdU: Critical temperature threshold (CCT) SD: Critical friction threshold (CFT)
2. Urticaria Control Test (UCT)
3. Complete response rate: Proportion of participants who are urticaria free based on UCT = 16
4. Well-controlled rate: Proportion of participants who are well controlled based on UCT ≥ 12
5. Time to complete response or well-controlled disease
6. Time to relapse
7. Serum PK concentration of briquilimab over time - Modelled serum PK parameters of briquilimab including but not limited to Cmax, Cmin and AUC as appropriate

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Jasper Therapeutics Inc.

Sponsor organisation

Jasper Therapeutics Inc.

Address

2200 Bridge Parkway Suite 102

City

Redwood City

Postcode

94065-1186

Country

United States

Scientific contact point

Organisation

Jasper Therapeutics Inc.

Contact name

Jasper Therapeutics Inc.

Public contact point

Organisation

Jasper Therapeutics Inc.

Contact name

Jasper Therapeutics Inc.

Third parties 13

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications