A Study to Assess Subcutaneous Lirentelimab (AK002) in Chronic Spontaneous Urticaria

Chronic Spontaneous Urticaria Clinical Trial

— MAVERICK  

Official title:

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lirentelimab in Adult Subjects With H-1 Antihistamine Refractory Chronic Spontaneous Urticaria

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05528861
• Other study ID #: AK002-027
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 26, 2022
• Est. completion date: May 2024

Study information

• Verified date: February 2024
• Source: Allakos Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous lirentelimab (AK002) in adult subjects with H-1 antihistamine refractory chronic spontaneous urticaria. Subjects who complete the randomized, double-blind, placebo-controlled treatment period may have the option to enroll in an open-label extension period and receive up to 6 doses of subcutaneous lirentelimab.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 127
• Est. completion date: May 2024
• Est. primary completion date: December 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Subject is able to understand the information on the study, has the capacity to consent, and has provided written informed consent.

2. Male and female subjects =18 years of age at the time of screening.

3. CSU diagnosis for =6 months.

4. Diagnosis of moderate-severe CSU refractory to H1-antihistamine (H1-AH) at a minimum of the licensed dose at the licensed frequency at the time of randomization as defined by the following: presence of hives and itch for =6 consecutive weeks prior to Screening Visit 1; UAS7 score (range 0-42) =16 and HSS7 score (range 0-21) =8 during the 7 days prior to randomization.

5. Subjects that are omalizumab-naïve or omalizumab-exposed.

6. Subjects must be on stable dose of H1-AH, between 1x and 4x of the licensed dose and at the licensed frequency, for treatment of CSU for at least 1 week prior to screening and willing to remain on a stable dose throughout the study.

7. Able and compliant with completing a daily symptom eDiary for the duration of the study and adherent to the study visit schedules.

Key Exclusion Criteria:

1. History of hypersensitivity to the study drugs or their excipients or to drugs of similar chemical classes (i.e., murine, chimeric or human antibodies).

2. Current use of biologics for any indication.

3. Demonstrated lack of primary response to treatment with a biologic therapy (e.g., omalizumab) for the treatment of CSU.

4. Use of any of the following treatments within 4 weeks prior to the baseline visit or any condition that in the opinion of the Investigator is likely to require such treatment(s) during the first 4 weeks of study treatment: (i) immunosuppressive or immunomodulatory drugs, including but not limited to systemic calcineurin inhibitors (e.g., cyclosporin, tacrolimus), mTOR inhibitors (e.g., sirolimus, everolimus), anti-metabolites (e.g., azathioprine, methotrexate, 6-mercaptopurine, leflunomide, mycophenolate mofetil), alkylating agents (e.g., cyclophosphamide), TNF inhibitors (e.g., infliximab, adalimumab), and eosinophil-depleting drugs (e.g., benralizumab, pramipexole); (ii) routine (daily or every other day during 5 or more consecutive days) doses of systemic hydroxychloroquine; (iii) intravenous immunoglobulin (IVIG); (iv) plasmapheresis.

5. Use of oral Janus kinase (JAK) inhibitors within 8 weeks of the baseline visit.

6. Use of any of the following treatments within 3 weeks prior to the baseline visit: (i) H2 antihistamines (H2-AH); (ii) routine (daily or every other day during 5 or more consecutive days) doses of systemic corticosteroids; (iii) regular (daily or every other day) doxepin (oral); (iv) leukotriene receptor antagonists (LTRA) (e.g., montelukast, zafirlukast).

7. H1-AH use at greater than approved doses or greater than local CSU guideline recommended doses after Screening Visit 1.

8. Previous treatment with biologics: (i) any cell-depleting agents including but not limited to rituximab within 6 months prior to the baseline visit or until lymphocyte count returns to normal, whichever is longer; (ii) other biologics, including investigational biologics (e.g., dupilumab, omalizumab, benralizumab, etc) within 5 half-lives if known or 8 weeks prior to the baseline visit, whichever is longer.

9. Planned or anticipated use of any prohibited medication.

10. Subjects having causes other than CSU for their urticaria including symptomatic dermographism, cholinergic urticaria, or any inducible urticaria.

11. Subjects with known or suspected urticarial vasculitis.

12. Subjects with known or suspected hereditary angioedema.

13. Any other skin disease associated with chronic itch, including atopic dermatitis, that in the Investigator's opinion might influence study outcome and subject's interpretation of symptoms caused by CSU.

14. A helminth parasitic infection diagnosed within 6 months prior to the date that informed consent is obtained and has not been treated with or has failed to respond to standard-of-care therapy.

15. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to study drug administration (or 90 days or 5 half-lives, whichever is longer, for biologic products).

16. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of study drug administration. This exclusion criterion does not apply to all types and formulations of vaccines (including live attenuated vaccines) currently authorized/approved by FDA or other regulatory authority for the prevention of COVID-19, which may be administered before, during, or after the study. The vaccine should not be administered within 3 days before and within 3 days after the administration of lirentelimab so that any side effects caused by either of the 2 medications can more easily be determined.

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Urticaria

Intervention

Drug:
• Lirentelimab (AK002)
Lirentelimab (AK002) is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Germany	Allakos Investigational Site 227-204	Augsburg
Germany	Allakos Investigational Site 227-201	Berlin
Germany	Allakos Investigational Site 227-214	Buxtehude
Germany	Allakos Investigational Site 227-205	Darmstadt
Germany	Allakos Investigational Site 227-209	Erlangen
Germany	Allakos Investigational Site 227-208	Frankfurt
Germany	Allakos Investigational Site 227-207	Langenau
Germany	Allakos Investigational Site 227-203	Leipzig
Germany	Allakos Investigational Site 227-202	Mainz
Germany	Allakos Investigational Site 227-210	Mainz
Germany	Allakos Investigational Site 227-211	Munich
Germany	Allakos Investigational Site 227-206	Osnabrück
Poland	Allakos Investigational Site 227-302	Lódz
Poland	Allakos Investigational Site 227-304	Lódz
Poland	Allakos Investigational Site 227-303	Lublin
Poland	Allakos Investigational Site 227-301	Zabrze
United States	Allakos Investigational Site 227-034	Ann Arbor	Michigan
United States	Allakos Investigational Site 227-002	Asheville	North Carolina
United States	Allakos Investigational Site 227-055	Austin	Texas
United States	Allakos Investigational Site 227-058	Bakersfield	California
United States	Allakos Investigational Site 227-019	Baltimore	Maryland
United States	Allakos Investigational Site 227-024	Birmingham	Alabama
United States	Allakos Investigational Site 227-045	Boise	Idaho
United States	Allakos Investigational Site 227-016	Boston	Massachusetts
United States	Allakos Investigational Site 227-022	Brooklyn	New York
United States	Allakos Investigational Site 227-013	Cincinnati	Ohio
United States	Allakos Investigational Site 227-029	Cincinnati	Ohio
United States	Allakos Investigational Site 227-006	Colorado Springs	Colorado
United States	Allakos Investigational Site 227-018	Columbus	Georgia
United States	Allakos Investigational Site 227-043	Columbus	Ohio
United States	Allakos Investigational Site 227-068	Cullman	Alabama
United States	Allakos Investigational Site 227-032	Detroit	Michigan
United States	Allakos Investigational Site 227-073	Dilworth	Minnesota
United States	Allakos Investigational Site 227-049	El Paso	Texas
United States	Allakos Investigational Site 227-070	Farmington Hills	Michigan
United States	Allakos Investigational Site 227-007	Great Neck	New York
United States	Allakos Investigational Site 227-033	Greenfield	Wisconsin
United States	Allakos Investigational Site 227-028	Hershey	Pennsylvania
United States	Allakos Investigational Site 227-036	Jacksonville	Florida
United States	Allakos Investigational Site 227-051	Lexington	Kentucky
United States	Allakos Investigational Site 227-009	Los Angeles	California
United States	Allakos Investigational Site 227-026	Los Angeles	California
United States	Allakos Investigational Site 227-062	Miami	Florida
United States	Allakos Investigational Site 227-011	Mission Viejo	California
United States	Allakos Investigational Site 227-059	Missoula	Montana
United States	Allakos Investigational Site 227-039	Murray	Utah
United States	Allakos Investigational Site 227-071	Murray	Utah
United States	Allakos Investigational Site 227-045	Normal	Illinois
United States	Allakos Investigational Site 227-066	North Charleston	South Carolina
United States	Allakos Investigational Site 227-060	Oklahoma City	Oklahoma
United States	Allakos Investigational Site 227-047	Overland Park	Kansas
United States	Allakos Investigational Site 227-040	Philadelphia	Pennsylvania
United States	Allakos Investigational Site 227-014	Phoenix	Arizona
United States	Allakos Investigational Site 227-074	Plainfield	Indiana
United States	Allakos Investigational Site 227-027	Portland	Oregon
United States	Allakos Investigational Site 227-057	River Forest	Illinois
United States	Allakos Investigational Site 227-052	Rochester	Minnesota
United States	Allakos Investigational Site 227-008	Saint Louis	Missouri
United States	Allakos Investigational Site 227-021	Santa Monica	California
United States	Allakos Investigational Site 227-041	Sarasota	Florida
United States	Allakos Investigational Site 227-023	Scottsdale	Arizona
United States	Allakos Investigational Site 227-005	Tampa	Florida
United States	Allakos Investigational Site 227-067	Tampa	Florida
United States	Allakos Investigational Site 227-064	Toledo	Ohio
United States	Allakos Investigational Site 227-012	Towson	Maryland
United States	Allakos Investigational Site 227-031	Upland	California
United States	Allakos Investigational Site 227-063	White Marsh	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Allakos Inc.

Countries where clinical trial is conducted

United States,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute change in UAS7 at Week 12	Weekly Urticaria Activity Score (UAS7; range 0-42; higher scores reflect greater disease activity)	Baseline to Week 12
Secondary	Absolute change in HSS7 at Week 12	Weekly Hives Severity Score (HSS7; range 0-21; higher scores reflect greater wheals)	Baseline to Week 12
Secondary	Absolute change in ISS7 at Week 12	Weekly Itch Severity Score (ISS7; range 0-21; higher scores reflect greater itching)	Baseline to Week 12
Secondary	Proportion of subjects achieving UAS7=0	Urticaria Activity Score (UAS7; range 0-42; higher scores reflect greater disease activity)	Baseline to Week 12