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

Allakos Inc.66 sites in 1 country127 target enrollmentOctober 26, 2022

ConditionsChronic Spontaneous Urticaria

InterventionsLirentelimab (AK002)Placebo

DrugsLirentelimab (AK002)

Overview

Phase: Phase 2
Intervention: Lirentelimab (AK002)
Conditions: Chronic Spontaneous Urticaria
Sponsor: Allakos Inc.
Enrollment: 127
Locations: 66
Primary Endpoint: Absolute Change in Weekly Urticaria Assessment Score (UAS7) From Baseline at Week 12
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 26, 2022

End Date

April 18, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Allakos Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subject is able to understand the information on the study, has the capacity to consent, and has provided written informed consent.
•Male and female subjects ≥18 years of age at the time of screening.
•CSU diagnosis for ≥6 months.
•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.
•Subjects that are omalizumab-naïve or omalizumab-exposed.
•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.
•Able and compliant with completing a daily symptom eDiary for the duration of the study and adherent to the study visit schedules.

Exclusion Criteria

•History of hypersensitivity to the study drugs or their excipients or to drugs of similar chemical classes (i.e., murine, chimeric or human antibodies).
•Current use of biologics for any indication.
•Demonstrated lack of primary response to treatment with a biologic therapy (e.g., omalizumab) for the treatment of CSU.
•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.
•Use of oral Janus kinase (JAK) inhibitors within 8 weeks of the baseline visit.
•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).
•H1-AH use at greater than approved doses or greater than local CSU guideline recommended doses after Screening Visit
•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.
•Planned or anticipated use of any prohibited medication.
•Subjects having causes other than CSU for their urticaria including symptomatic dermographism, cholinergic urticaria, or any inducible urticaria.

Arms & Interventions

Lirentelimab (AK002)

Subjects in this arm will receive lirentelimab (AK002) administered subcutaneously.

Intervention: Lirentelimab (AK002)

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Absolute Change in Weekly Urticaria Assessment Score (UAS7) From Baseline at Week 12

Time Frame: Baseline to Week 12

The UAS7 is the sum for 7 days of the daily Hives Severity Score (HSS) and the daily Itch Severity Score (ISS). The daily HSS is recorded on a scale of 0 (none) to 3 (\>50 hives) and the daily ISS is recorded on a scale of 0 (none) to 3 (severe). Therefore, the possible range of the weekly UAS7 score is 0-42, with 42 being the most severe.

Secondary Outcomes

Absolute Change in Hives Severity Score (HSS7) From Baseline at Week 12(Baseline to Week 12)
Absolute Change in Itch Severity Score (ISS7) From Baseline at Week 12(Baseline to Week 12)
Proportion of Subjects Achieving Weekly Urticaria Assessment Score (UAS7)=0 at Week 12(At Week 12)