Study to Assess the Safety, Tolerability, Pharmacokinetics and Immunogenicity of AK006 in Healthy Subjects and Subjects With Chronic Spontaneous Urticaria

Allakos

Status and phase: Active, not recruiting; Phase 1

Conditions: Healthy Participants; Chronic Spontaneous Urticaria

Treatments: Drug: AK006-SC; Drug: AK006-IV; Drug: Placebo-IV; Drug: Placebo-SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT06072157

AK006-001

Details and patient eligibility

About

This is a Phase 1, randomized, double-blind, placebo-controlled, sequential, single- and multiple-ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of intravenous (IV) infusions and a single subcutaneous (SC) injection of AK006. The study will be conducted in 4 parts: a single-ascending dose part (Part A) in healthy participants, a multiple-ascending dose part (Part B) in healthy participants with an expanded cohort (Part C) in participants with chronic spontaneous urticaria (CSU), and a single ascending dose SC injection cohort (Part D) in healthy participants.

Enrollment: 136 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

To be included in the study, the participant must:

• Weigh between 60 and 120 kg (inclusive) and have a body mass index (BMI) between 20 and 32 kg/m2, inclusive
• Agree (female of childbearing potential or male with female partner of childbearing potential) to use a highly effective method (<1% failure rate) of birth control, if sexually active from screening and for 16 weeks after the last dose of investigational product (IP).

Additionally, to be included in Part A, B and D, the participant must:

• Be in good general health with no significant medical history and has no clinically significant abnormalities on physical examination

Additionally, to be included in Part C, the participant must:

• Have a diagnosis of chronic spontaneous urticaria (CSU) for at least 6 months prior to screening

• Has a diagnosis of moderate to severe CSU that is refractory to stable doses of a single 2nd or later generation H1-AH between 1× and 4× the licensed dose and frequency at the time of randomization as defined by the following:

  • Presence of hives and itch for ≥6 consecutive weeks at any time prior to the Screening, despite the use of non-sedating H1-AHs. Note: Subject must be on a non-sedating H1-AH for treatment of CSU symptoms at the time of the Screening visit.
  • UAS7 score ≥16 with a HSS7 score ≥8 for the 2 consecutive weeks prior to randomization (Day 1) while on the stable dose of an H1-AH.

• Be on a stable dose of a single 2nd or later generation H1-antihistamines for the treatment of CSU, between 1× and 4× the licensed dose and frequency, by Day -14 of the Screening Period and must be willing to remain on the same stable dose throughout the study.

• Able and willing to complete a daily electronic diary to collect CSU symptoms for the duration of the study.

Key Exclusion Criteria:

A participant who meets any of the following exclusion criteria will not be eligible for inclusion in the study:

• Female participants who are pregnant, lactating, or planning to become pregnant during the study.
• Abnormal laboratory values, or findings in physical examination, ECG (QTc >450 ms for males and >470 ms for females), or vital signs considered to be clinically significant by the investigator.

Additionally, a participant will be excluded from Part A, B and D, if:

• Received treatment with any prescribed (excluding hormonal contraceptives or hormone replacement therapy [post-menopausal females]) or nonprescribed systemic or topical medication (including herbal product, and vitamins) within 21 days prior to the first dose of IP (excluding acetaminophen).

Additionally, a participant will be excluded from Part C, if:

• Has known or suspected urticarial vasculitis
• Subject has causes other than CSU for their urticaria including symptomatic dermographism, cholinergic urticaria, or any inducible urticaria
• Subject has other conditions or diseases that in the investigator's opinion might influence study evaluations and results
• Has any disease or condition (medical or surgical) which, in the opinion of the investigator, or medical monitor, would place the subject at increased risk

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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136 participants in 4 patient groups

Part A - Single Ascending Dose (SAD) Intravenous Cohorts

Experimental group

Description:

Part A: Healthy adult participants will receive a single intravenous infusion of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 5 cohorts evaluated.

Treatment:

Drug: Placebo-IV

Drug: AK006-IV

Part B - Multiple Ascending Dose (MAD) Intravenous Cohorts

Experimental group

Description:

Part B: Healthy adult participants will receive multiple intravenous infusions of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 3 cohorts evaluated.

Treatment:

Drug: Placebo-IV

Drug: AK006-IV

Part C - Multiple Dose Intravenous Cohort

Experimental group

Description:

Part C: Adults with Chronic Spontaneous Urticaria will receive multiple intravenous infusions of AK006 or matching placebo.

Treatment:

Drug: Placebo-IV

Drug: AK006-IV

Part D - Single Ascending Dose (SAD) Subcutaneous Cohorts

Experimental group

Description:

Part D: Healthy adult participants will receive a single subcutaneous injection of AK006 or matching placebo. The dose of AK006 will be increased per cohort. There will be up to 2 cohorts evaluated.

Treatment:

Drug: Placebo-SC

Drug: AK006-SC