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

NCT06072157 | Completed Phase 1 FDA Drug

• 1 other identifier: AK006-001
• Study Type: interventional
• Target: 136
• Locations: 2 countries
• Sites: 25

Brief Summary

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.

Conditions

Healthy Participants; Chronic Spontaneous Urticaria

Outcome Measures

Primary Outcomes (4)

• Incidence and severity of adverse events (AEs)

  AEs, serious AEs, and treatment emergent AEs (AE that starts after start of investigational product)

  Screening to Day 113 (Part A and D), Screening to Day 141 (Part B), and Screening to Day 197 (Part C)

• Incidence of AEs of special interest

  Infusion-related reactions, injection-related reactions, injection site reactions, anaphylaxis, and opportunistic infections

  Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)

• AEs leading to discontinuation

  AEs

  Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)

• Incidence of clinically significant abnormal laboratory values, electrocardiograms (ECGs), and vital signs

  Incidence of clinically significant abnormal laboratory values, electrocardiograms (ECGs), and vital signs

  Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)

Secondary Outcomes (14)

• AK006 serum concentration at end of IV infusion

  Day 1 (Part A) and Day 29 (Part B)

• AK006 area under the concentration-time curve (AUC) from time 0 to the time of last quantifiable concentration (AUC[0-last])

  Day 1 to Day 113 (Part A and D) and Day 29 to Day 141 (Part B)

• AK006 AUC from time 0 extrapolated to infinity (AUC[0-inf])

  Day 1 to Day 113 (Part A and D)

• Total systemic clearance of AK006 after intravenous or subcutaneous dose (CL)

  Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B)

• Systemic steady-state volume of distribution (Vss) of AK006

  Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B)

Study Arms (4)

Part A - Single Ascending Dose (SAD) Intravenous Cohorts

EXPERIMENTAL

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.

Drug: AK006-IV; Drug: Placebo-IV

Part B - Multiple Ascending Dose (MAD) Intravenous Cohorts

EXPERIMENTAL

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.

Drug: AK006-IV; Drug: Placebo-IV

Part C - Multiple Dose Intravenous Cohort

EXPERIMENTAL

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

Drug: AK006-IV; Drug: Placebo-IV

Part D - Single Ascending Dose (SAD) Subcutaneous Cohorts

EXPERIMENTAL

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.

Drug: AK006-SC; Drug: Placebo-SC

Interventions

AK006-IV DRUG

Intravenous infusion

Part A - Single Ascending Dose (SAD) Intravenous Cohorts; Part B - Multiple Ascending Dose (MAD) Intravenous Cohorts; Part C - Multiple Dose Intravenous Cohort

Placebo-IV DRUG

Intravenous infusion

Part A - Single Ascending Dose (SAD) Intravenous Cohorts; Part B - Multiple Ascending Dose (MAD) Intravenous Cohorts; Part C - Multiple Dose Intravenous Cohort

AK006-SC DRUG

Subcutaneous

Part D - Single Ascending Dose (SAD) Subcutaneous Cohorts

Placebo-SC DRUG

Subcutaneous

Part D - Single Ascending Dose (SAD) Subcutaneous Cohorts

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Allakos Inc.: lead

Study Sites (25)

Site 601-001 Healthy Volunteer Clinical Research Unit (Part A, B and D)

Anniston, Alabama, 36207, United States

Location

Site 601-004 (Part C)

Birmingham, Alabama, 35209, United States

Location

Site 601-008 (Part C)

Scottsdale, Arizona, 85251, United States

Location

Site 601-014 (Part C)

Bakersfield, California, 93301, United States

Location

Site 601-007 (Part C)

Encino, California, 91436, United States

Location

Site 601-015 (Part C)

Upland, California, 91786, United States

Location

Site 601-016 (Part C)

Colorado Springs, Colorado, 80907, United States

Location

Site 601-006 (Part C)

Overland Park, Kansas, 66211, United States

Location

Site 601-019 (Part C)

Lexington, Kentucky, 40509, United States

Location

Site 601-003 (Part C)

Baltimore, Maryland, 21224, United States

Location

Site 601-012 (Part C)

Boston, Massachusetts, 02111, United States

Location

Site 601-023 (Part C)

Troy, Michigan, 48084, United States

Location

Site 601-011 (Part C)

St Louis, Missouri, 63141, United States

Location

Site 601-020 (Part C)

Brooklyn, New York, 11203, United States

Location

Site 601-017 (Part C)

Fargo, North Dakota, 58103, United States

Location

Site 601-002 (Part C)

Cincinnati, Ohio, 45236, United States

Location

Site 601-018 (Part C)

Portland, Oregon, 97201, United States

Location

Site 601-010 (Part C)

El Paso, Texas, 79912, United States

Location

Site 601-013 (Part C)

Greenfield, Wisconsin, 53228, United States

Location

Site 601-106 (Part C)

Calgary, Alberta, T2M 1A6, Canada

Location

Site 601-103 (Part C)

London, Ontario, N6H 5L5, Canada

Location

Site 601-107 (Part C)

Niagara Falls, Ontario, L2H 1H5, Canada

Location

Site 601-108 (Part C)

Toronto, Ontario, M5G 1E2, Canada

Location

Site 601-102 (Part C)

Québec, Quebec, G1V 4W2, Canada

Location

Site 601-105 (Part C)

Québec, Quebec, G1W 4R4, Canada

Location

Related Publications (1)

• O'Sullivan JA, Youngblood BA, Schleimer RP, Bochner BS. Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases. Semin Immunol. 2023 Sep;69:101799. doi: 10.1016/j.smim.2023.101799. Epub 2023 Jul 4.

  PMID: 37413923 BACKGROUND

MeSH Terms

Conditions

Chronic Urticaria

Condition Hierarchy (Ancestors)

Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind (placebo) essentially identical in appearance to the investigational drug (AK006)
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single (Part A) and multiple (Part B) ascending IV dose study in healthy participants with a multiple dose expansion (Part C) in participants with chronic spontaneous urticaria. Single ascending (Part D) subcutaneous (SC) dose study in healthy participants

Study Record Dates

• First Submitted: September 9, 2023
• First Posted: October 10, 2023
• Study Start: August 28, 2023
• Primary Completion: May 12, 2025
• Study Completion: May 12, 2025
• Last Updated: June 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (19); CA (6)