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

Phase 1

• Conditions: Chronic spontaneous urticaria; MedDRA version: 20.0Level: PTClassification code 10072757Term: Chronic spontaneous urticariaSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

• Registration Number: EUCTR2022-001847-26-DE
• Lead Sponsor: Allakos Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-11-18
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

Subjects with CSU are eligible to enroll in the study if they meet all of the following 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-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 consecutive days prior to screening Day -7 Phone Visit and during the 7 consecutive days prior to randomization (Day 1).
5) Subjects that are omalizumab-naïve or omalizumab-exposed. Omalizumab-exposed subjects are those that have demonstrated secondary loss of response, intolerance, or lack of access to biologics due to economic reasons.
6) Subjects must be on a stable dose of H1-AH, between 1× and 4× of the licensed dose and at the licensed dosing 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.
8) Female subjects must be either postmenopausal (defined as no menses for 12 months without an alternative medical cause) with FSH level >30 mIU/mL at screening or surgically sterile (tubal ligation, hysterectomy, or bilateral oophorectomy) for at least 3 months or, if of childbearing potential, have a negative serum pregnancy test and agree to use a highly effective method of contraception as defined in this protocol or abstain from sexual activity, if compliant with preferred and usual lifestyle of the subject from screening until the end of the study or for 120 days following the last dose of study drug, whichever is longer.
In the case of a postmenopausal female subject with FSH level =30 mIU/mL at screening, the subject will be required to have a negative serum pregnancy test during the screening period and will also be required to have a negative urine dipstick pregnancy test prior to dosing and at each study visit.
9) Male subjects with female partners of childbearing potential must agree to use a highly effective method of contraception as defined in this protocol or abstain from sexual activity from screening until the end of the study or for 120 days following the last dose of study drug, whichever is longer. All fertile men with female partners of childbearing potential should be instructed to contact the Investigator immediately if they suspect their partner might be pregnant (e.g., missed or late menstrual period) at any time during study participation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1) History of hypersensitivity to the study drugs or their excipients or to drugs of similar chemical classes.
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, defined as no response to treatment despite complete adherence to a prescribed regimen (e.g., a stable dose of omalizumab at =300 mg per month) for at least 3 months, based on interview at screening.
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:
- Immunosuppressive or immunomodulatory drugs, including but not limited to systemic calcineurin inhibitors, mTOR inhibitors, anti-metabolites, alkylating agents (e.g., cyclophosphamide), and eosinophil-depleting drugs (e.g., pramipexole).
- Routine (daily or every other day during 5 or more consecutive days) doses of systemic hydroxychloroquine
- Plasmapheresis
5) Use of oral Janus kinase (JAK) inhibitors within 8 weeks of the baseline visit (requires discussion with Medical Monitor prior to subject enrolling in study).
6) Use of any of the following treatments within 3 weeks prior to the baseline visit:
- H2-AH
- Routine (daily or every other day during 5 or more consecutive days) doses of systemic corticosteroids
- Regular (daily or every other day) doxepin (oral)
- 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 or intravenous immunoglobulin:
- 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.
- Other biologics, including investigational biologics (e.g., dupilumab, omalizumab, benralizumab, etc.) and TNF inhibitors (e.g., infliximab, adalimumab) within 5 half-lives if known or 8 weeks prior to baseline visit, whichever is longer.
- Intravenous immunoglobulin (IVIG) within 5 half-lives
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) Diseases other than chronic urticaria with urticarial or angioedema symptoms, including chronic itching, that in the Investigator’s opinion might influence study evaluations and results.
12) Subjects with known or suspected urticarial vasculitis.
13) Subjects with known or suspected hereditary angioedema.
14) 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.
15) 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.
16) Evidence of active HIV infection at screening based on serology or evidence of active hepatitis B or C at screening based on serology.
17)Presence of an abnormal screening laboratory value considered to be clinically significant by the Investigator.
18) Known or suspected history of alcohol, drug, or other substance abuse or dependence that

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified