Clinical trial NCT05528861: A Study to Assess Subcutaneous Lirentelimab (AK002) in Chronic Spontaneous Urticaria
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Spontaneous Urticaria
Keywords: Chronic Spontaneous Urticaria
Chronic Urticaria
Urticaria
Chronic Idiopathic Urticaria
Chronic Autoimmune Urticaria
Idiopathic Chronic Urticaria
Autoimmune Urticaria
Lead sponsor: Allakos Inc.
Sponsor class: INDUSTRY
First posted: 2022-09-06
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Absolute Change in Weekly Urticaria Assessment Score (UAS7) From Baseline at Week 12
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Absolute Change in Hives Severity Score (HSS7) From Baseline at Week 12
timeFrame: Baseline to Week 12
measure: Absolute Change in Itch Severity Score (ISS7) From Baseline at Week 12
timeFrame: Baseline to Week 12
measure: Proportion of Subjects Achieving Weekly Urticaria Assessment Score (UAS7)=0 at Week 12
timeFrame: At Week 12
Other outcomes:
measure: Safety and Tolerability of up to 6 Doses of Open-label AK002 in Subjects With Chronic Spontaneous Urticaria in the Open-label Extension Period
timeFrame: Through study completion, up to 34 weeks (open-label extension period)
Locations:
city: Birmingham
country: United States
facility: Allakos Investigational Site 227-024
state: Alabama
city: Cullman
country: United States
facility: Allakos Investigational Site 227-068
state: Alabama
city: Phoenix
country: United States
facility: Allakos Investigational Site 227-014
state: Arizona
city: Scottsdale
country: United States
facility: Allakos Investigational Site 227-023
state: Arizona
city: Bakersfield
country: United States
facility: Allakos Investigational Site 227-058
state: California
city: Los Angeles
country: United States
facility: Allakos Investigational Site 227-026
state: California
city: Los Angeles
country: United States
facility: Allakos Investigational Site 227-009
state: California
city: Mission Viejo
country: United States
facility: Allakos Investigational Site 227-011
state: California
city: Santa Monica
country: United States
facility: Allakos Investigational Site 227-021
state: California
city: Upland
country: United States
facility: Allakos Investigational Site 227-031
state: California
city: Colorado Springs
country: United States
facility: Allakos Investigational Site 227-006
state: Colorado
city: Jacksonville
country: United States
facility: Allakos Investigational Site 227-036
state: Florida
city: Miami
country: United States
facility: Allakos Investigational Site 227-062
state: Florida
city: Sarasota
country: United States
facility: Allakos Investigational Site 227-041
state: Florida
city: Tampa
country: United States
facility: Allakos Investigational Site 227-067
state: Florida
city: Tampa
country: United States
facility: Allakos Investigational Site 227-005
state: Florida
city: Columbus
country: United States
facility: Allakos Investigational Site 227-018
state: Georgia
city: Boise
country: United States
facility: Allakos Investigational Site 227-045
state: Idaho
city: Normal
country: United States
facility: Allakos Investigational Site 227-045
state: Illinois
city: River Forest
country: United States
facility: Allakos Investigational Site 227-057
state: Illinois
city: Plainfield
country: United States
facility: Allakos Investigational Site 227-074
state: Indiana
city: Overland Park
country: United States
facility: Allakos Investigational Site 227-047
state: Kansas
city: Lexington
country: United States
facility: Allakos Investigational Site 227-051
state: Kentucky
city: Baltimore
country: United States
facility: Allakos Investigational Site 227-019
state: Maryland
city: Towson
country: United States
facility: Allakos Investigational Site 227-012
state: Maryland
city: White Marsh
country: United States
facility: Allakos Investigational Site 227-063
state: Maryland
city: Boston
country: United States
facility: Allakos Investigational Site 227-016
state: Massachusetts
city: Ann Arbor
country: United States
facility: Allakos Investigational Site 227-034
state: Michigan
city: Detroit
country: United States
facility: Allakos Investigational Site 227-032
state: Michigan
city: Farmington Hills
country: United States
facility: Allakos Investigational Site 227-070
state: Michigan
city: Dilworth
country: United States
facility: Allakos Investigational Site 227-073
state: Minnesota
city: Rochester
country: United States
facility: Allakos Investigational Site 227-052
state: Minnesota
city: Saint Louis
country: United States
facility: Allakos Investigational Site 227-008
state: Missouri
city: Missoula
country: United States
facility: Allakos Investigational Site 227-059
state: Montana
city: Brooklyn
country: United States
facility: Allakos Investigational Site 227-022
state: New York
city: Great Neck
country: United States
facility: Allakos Investigational Site 227-007
state: New York
city: Asheville
country: United States
facility: Allakos Investigational Site 227-002
state: North Carolina
city: Cincinnati
country: United States
facility: Allakos Investigational Site 227-013
state: Ohio
city: Cincinnati
country: United States
facility: Allakos Investigational Site 227-029
state: Ohio
city: Columbus
country: United States
facility: Allakos Investigational Site 227-043
state: Ohio
city: Toledo
country: United States
facility: Allakos Investigational Site 227-064
state: Ohio
city: Oklahoma City
country: United States
facility: Allakos Investigational Site 227-060
state: Oklahoma
city: Portland
country: United States
facility: Allakos Investigational Site 227-027
state: Oregon
city: Hershey
country: United States
facility: Allakos Investigational Site 227-028
state: Pennsylvania
city: Philadelphia
country: United States
facility: Allakos Investigational Site 227-040
state: Pennsylvania
city: North Charleston
country: United States
facility: Allakos Investigational Site 227-066
state: South Carolina
city: Austin
country: United States
facility: Allakos Investigational Site 227-055
state: Texas
city: El Paso
country: United States
facility: Allakos Investigational Site 227-049
state: Texas
city: Murray
country: United States
facility: Allakos Investigational Site 227-039
state: Utah
city: Murray
country: United States
facility: Allakos Investigational Site 227-071
state: Utah
city: Greenfield
country: United States
facility: Allakos Investigational Site 227-033
state: Wisconsin
city: Augsburg
country: Germany
facility: Allakos Investigational Site 227-204
city: Berlin
country: Germany
facility: Allakos Investigational Site 227-201
city: Buxtehude
country: Germany
facility: Allakos Investigational Site 227-214
city: Darmstadt
country: Germany
facility: Allakos Investigational Site 227-205
city: Erlangen
country: Germany
facility: Allakos Investigational Site 227-209
city: Frankfurt
country: Germany
facility: Allakos Investigational Site 227-208
city: Langenau
country: Germany
facility: Allakos Investigational Site 227-207
city: Leipzig
country: Germany
facility: Allakos Investigational Site 227-203
city: Mainz
country: Germany
facility: Allakos Investigational Site 227-210
city: Mainz
country: Germany
facility: Allakos Investigational Site 227-202
city: Munich
country: Germany
facility: Allakos Investigational Site 227-211
city: Osnabrück
country: Germany
facility: Allakos Investigational Site 227-206
city: Lublin
country: Poland
facility: Allakos Investigational Site 227-303
city: Zabrze
country: Poland
facility: Allakos Investigational Site 227-301
city: Łódź
country: Poland
facility: Allakos Investigational Site 227-302
city: Łódź
country: Poland
facility: Allakos Investigational Site 227-304
Study officials:
affiliation: Allakos Inc.
name: Chin Lee, MD, MPH
role: STUDY_DIRECTOR
References: