Clinical trial NCT06072157: Study to Assess the Safety, Tolerability, Pharmacokinetics and Immunogenicity of AK006 in Healthy Subjects and Subjects With Chronic Spontaneous Urticaria
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Chronic Spontaneous Urticaria
Lead sponsor: Allakos Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-10
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Incidence and severity of adverse events (AEs)
timeFrame: Screening to Day 113 (Part A and D), Screening to Day 141 (Part B), and Screening to Day 197 (Part C)
measure: Incidence of AEs of special interest
timeFrame: Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)
measure: AEs leading to discontinuation
timeFrame: Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)
measure: Incidence of clinically significant abnormal laboratory values, electrocardiograms (ECGs), and vital signs
timeFrame: 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:
measure: AK006 serum concentration at end of IV infusion
timeFrame: Day 1 (Part A) and Day 29 (Part B)
measure: AK006 area under the concentration-time curve (AUC) from time 0 to the time of last quantifiable concentration (AUC[0-last])
timeFrame: Day 1 to Day 113 (Part A and D) and Day 29 to Day 141 (Part B)
measure: AK006 AUC from time 0 extrapolated to infinity (AUC[0-inf])
timeFrame: Day 1 to Day 113 (Part A and D)
measure: Total systemic clearance of AK006 after intravenous or subcutaneous dose (CL)
timeFrame: Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B)
measure: Systemic steady-state volume of distribution (Vss) of AK006
timeFrame: Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B)
measure: AK006 Terminal elimination phase half-life (t1/2)
timeFrame: Day 1 to Day 113 (Part A and D) and Day 1 to Day 141 (Part B)
measure: Predose AK006 serum concentration (Ctrough, before the next dose) (Part B)
timeFrame: Day 29 (pre-dose)
measure: AK006 AUC(0-last) after the second dose (Part B)
timeFrame: Day 29 to Day 141
measure: AK006 AUC over the dosing time interval (time 0 to 28 days) (AUC[tau]) (Part B)
timeFrame: Day 1 to Day 28 with each dosing interval
measure: AK006 serum concentrations
timeFrame: Up to Day 141 (Part A, B, D); Up to Day 197 (Part C)
measure: AK006 absolute bioavailability subcutaneous injection
timeFrame: Day 1 to Day 113 (Part A and D)
measure: AK006 PK dose proportionality (Part A, B, D)
timeFrame: Up to Day 141
measure: AK006 PK dose stationarity (Part B)
timeFrame: Up to Day 141
measure: AK006 Anti-drug Antibodies (ADAs)
timeFrame: Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B) and Day 1 to Day 197 (Part C)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Site 601-001 Healthy Volunteer Clinical Research Unit (Part A, B and D)
state: Alabama
city: Birmingham
country: United States
facility: Site 601-004 (Part C)
state: Alabama
city: Scottsdale
country: United States
facility: Site 601-008 (Part C)
state: Arizona
city: Bakersfield
country: United States
facility: Site 601-014 (Part C)
state: California
city: Encino
country: United States
facility: Site 601-007 (Part C)
state: California
city: Upland
country: United States
facility: Site 601-015 (Part C)
state: California
city: Colorado Springs
country: United States
facility: Site 601-016 (Part C)
state: Colorado
city: Overland Park
country: United States
facility: Site 601-006 (Part C)
state: Kansas
city: Lexington
country: United States
facility: Site 601-019 (Part C)
state: Kentucky
city: Baltimore
country: United States
facility: Site 601-003 (Part C)
state: Maryland
city: Boston
country: United States
facility: Site 601-012 (Part C)
state: Massachusetts
city: Troy
country: United States
facility: Site 601-023 (Part C)
state: Michigan
city: Saint Louis
country: United States
facility: Site 601-011 (Part C)
state: Missouri
city: Brooklyn
country: United States
facility: Site 601-020 (Part C)
state: New York
city: Fargo
country: United States
facility: Site 601-017 (Part C)
state: North Dakota
city: Cincinnati
country: United States
facility: Site 601-002 (Part C)
state: Ohio
city: Portland
country: United States
facility: Site 601-018 (Part C)
state: Oregon
city: El Paso
country: United States
facility: Site 601-010 (Part C)
state: Texas
city: Greenfield
country: United States
facility: Site 601-013 (Part C)
state: Wisconsin
city: Calgary
country: Canada
facility: Site 601-106 (Part C)
state: Alberta
city: London
country: Canada
facility: Site 601-103 (Part C)
state: Ontario
city: Niagara Falls
country: Canada
facility: Site 601-107 (Part C)
state: Ontario
city: Toronto
country: Canada
facility: Site 601-108 (Part C)
state: Ontario
city: Québec
country: Canada
facility: Site 601-102 (Part C)
state: Quebec
city: Québec
country: Canada
facility: Site 601-105 (Part C)
state: Quebec
Study officials:
References:
citation: 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.