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

Healthy Participants Clinical Trial

Official title:

A Phase 1, Double-Blind, Randomized, Placebo-Controlled, Sequential, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of AK006 in Healthy Subjects and in Subjects With H1 Antihistamine Refractory Chronic Spontaneous Urticaria

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06072157
• Other study ID #: AK006-001
• Status: Recruiting
• Phase: Phase 1
• Start date: August 28, 2023
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Allakos Inc.
• Contact: AK006 Study Team
• Phone: 650-542-0421
• Email: AK006ClinicalStudies[@]allakos.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 148
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Spontaneous Urticaria
• Chronic Urticaria
• Healthy Participants
• Urticaria

Intervention

Drug:
• AK006-IV
Intravenous infusion
• Placebo-IV
Intravenous infusion
• AK006-SC
Subcutaneous
• Placebo-SC
Subcutaneous

Locations

Country	Name	City	State
Canada	Site 601-103 (Part C)	London	Ontario
Canada	Site 601-107 (Part C)	Niagara Falls	Ontario
Canada	Site 601-102 (Part C)	Québec	Quebec
Canada	Site 601-105 (Part C)	Québec	Quebec
Canada	Site 601-108 (Part C)	Toronto	Ontario
United States	Site 601-001 Healthy Volunteer Clinical Research Unit (Part A, B and D)	Anniston	Alabama
United States	Site 601-014 (Part C)	Bakersfield	California
United States	Site 601-004 (Part C)	Birmingham	Alabama
United States	Site 601-012 (Part C)	Boston	Massachusetts
United States	Site 601-020 (Part C)	Brooklyn	New York
United States	Site 601-002 (Part C)	Cincinnati	Ohio
United States	Site 601-016 (Part C)	Colorado Springs	Colorado
United States	Site 601-010 (Part C)	El Paso	Texas
United States	Site 601-007 (Part C)	Encino	California
United States	Site 601-017 (Part C)	Fargo	North Dakota
United States	Site 601-013 (Part C)	Greenfield	Wisconsin
United States	Site 601-019 (Part C)	Lexington	Kentucky
United States	Site 601-006 (Part C)	Overland Park	Kansas
United States	Site 601-018 (Part C)	Portland	Oregon
United States	Site 601-011 (Part C)	Saint Louis	Missouri
United States	Site 601-008 (Part C)	Scottsdale	Arizona
United States	Site 601-023 (Part C)	Troy	Michigan
United States	Site 601-015 (Part C)	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Allakos Inc.

Countries where clinical trial is conducted

United States,  Canada, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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	AK006 serum concentration at end of IV infusion	AK006 Serum concentration (ng/mL) at end of infusion	Day 1 (Part A) and Day 29 (Part B)
Secondary	AK006 area under the concentration-time curve (AUC) from time 0 to the time of last quantifiable concentration (AUC[0-last])	AK006 AUC(0-last) (ng x h/mL)	Day 1 to Day 113 (Part A and D) and Day 29 to Day 141 (Part B)
Secondary	AK006 AUC from time 0 extrapolated to infinity (AUC[0-inf])	AK006 AUC(0-inf) (ng x h/mL)	Day 1 to Day 113 (Part A and D)
Secondary	Total systemic clearance of AK006 after intravenous or subcutaneous dose (CL)	AK006 CL (L/h/kg)	Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B)
Secondary	Systemic steady-state volume of distribution (Vss) of AK006	AK006 Vss (mg/L)	Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B)
Secondary	AK006 Terminal elimination phase half-life (t1/2)	AK006 t1/2 (hours)	Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B)
Secondary	Predose AK006 serum concentration (Ctrough, before the next dose) (Part B)	AK006 Ctrough (ng/mL)	Day 29 (pre-dose)
Secondary	AK006 AUC(0-last) after the second dose (Part B)	AK006 AUC(0-last) (ng x h/mL)	Day 29 to Day 141
Secondary	AK006 AUC over the dosing time interval (time 0 to 28 days) (AUC[tau]) (Part B)	AK006 AUC(tau) (ng x h/mL)	Day 1 to Day 28 with each dosing interval
Secondary	AK006 serum concentrations	AK006 ng/mL	Day 1 to Day 141
Secondary	AK006 absolute bioavailability subcutaneous injection	Ratio of mean AUC(0-last) after subcutaneous injection to mean AUC(0-last) after intravenous administration adjusted for dose	Day 1 to Day 113 (Part A and D)
Secondary	AK006 PK dose proportionality (Part A, B, D)	Comparing dose-normalized Cmax and AUC (Part A, B, and D)	Up to Day 141
Secondary	AK006 PK dose stationarity (Part B)	Comparing AUCtau from last dose to AUCtau from first dose	Up to Day 141
Secondary	AK006 Anti-drug Antibodies (ADAs)	Number of participants with positive or negative AK006-ADAs	Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B) and Day 1 to Day 197 (Part C)