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

Phase 1

Recruiting

• Conditions: Healthy Participants; Chronic Spontaneous Urticaria
• Interventions: Drug: AK006-IV; Drug: AK006-SC; Drug: Placebo-IV; Drug: Placebo-SC

• Registration Number: NCT06072157
• Lead Sponsor: Allakos Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-08-28
• Study First Submitted: 2023-09-09
• Study First Submitted QC: 2023-10-02
• Study First Posted: 2023-10-10
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-26
• Last Update Posted: 2024-09-27
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 148

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A - Single Ascending Dose (SAD) Intravenous Cohorts	Placebo-IV	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.
Part B - Multiple Ascending Dose (MAD) Intravenous Cohorts	AK006-IV	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.
Part A - Single Ascending Dose (SAD) Intravenous Cohorts	AK006-IV	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.
Part B - Multiple Ascending Dose (MAD) Intravenous Cohorts	Placebo-IV	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.
Part C - Multiple Dose Intravenous Cohort	AK006-IV	Part C: Adults with Chronic Spontaneous Urticaria will receive multiple intravenous infusions of AK006 or matching placebo.
Part C - Multiple Dose Intravenous Cohort	Placebo-IV	Part C: Adults with Chronic Spontaneous Urticaria will receive multiple intravenous infusions of AK006 or matching placebo.
Part D - Single Ascending Dose (SAD) Subcutaneous Cohorts	AK006-SC	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.
Part D - Single Ascending Dose (SAD) Subcutaneous Cohorts	Placebo-SC	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.

Primary Outcome Measures

Name	Time	Method
AEs leading to discontinuation	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
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)	Incidence of clinically significant abnormal laboratory values, electrocardiograms (ECGs), and vital signs
Incidence and severity of adverse events (AEs)	Screening to Day 113 (Part A and D), Screening to Day 141 (Part B), and Screening to Day 197 (Part C)	AEs, serious AEs, and treatment emergent AEs (AE that starts after start of investigational product)
Incidence of AEs of special interest	Day 1 to Day 113 (Part A and D), Day 1 to Day 141 (Part B), and Day 1 to Day 197 (Part C)	Infusion-related reactions, injection-related reactions, injection site reactions, anaphylaxis, and opportunistic infections

Secondary Outcome Measures

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

Trial Locations

Locations (25)

Site 601-001 Healthy Volunteer Clinical Research Unit (Part A, B and D); 🇺🇸 Anniston, Alabama, United States

Site 601-004 (Part C); 🇺🇸 Birmingham, Alabama, United States

Site 601-008 (Part C); 🇺🇸 Scottsdale, Arizona, United States

Site 601-014 (Part C); 🇺🇸 Bakersfield, California, United States

Site 601-007 (Part C); 🇺🇸 Encino, California, United States

Site 601-015 (Part C); 🇺🇸 Upland, California, United States

Site 601-016 (Part C); 🇺🇸 Colorado Springs, Colorado, United States

Site 601-006 (Part C); 🇺🇸 Overland Park, Kansas, United States

Site 601-019 (Part C); 🇺🇸 Lexington, Kentucky, United States

Site 601-003 (Part C); 🇺🇸 Baltimore, Maryland, United States

Site 601-012 (Part C); 🇺🇸 Boston, Massachusetts, United States

Site 601-023 (Part C); 🇺🇸 Troy, Michigan, United States

Site 601-011 (Part C); 🇺🇸 Saint Louis, Missouri, United States

Site 601-020 (Part C); 🇺🇸 Brooklyn, New York, United States

Site 601-017 (Part C); 🇺🇸 Fargo, North Dakota, United States

Site 601-002 (Part C); 🇺🇸 Cincinnati, Ohio, United States

Site 601-018 (Part C); 🇺🇸 Portland, Oregon, United States

Site 601-010 (Part C); 🇺🇸 El Paso, Texas, United States

Site 601-013 (Part C); 🇺🇸 Greenfield, Wisconsin, United States

Site 601-106 (Part C); 🇨🇦 Calgary, Alberta, Canada

Site 601-103 (Part C); 🇨🇦 London, Ontario, Canada

Site 601-107 (Part C); 🇨🇦 Niagara Falls, Ontario, Canada

Site 601-108 (Part C); 🇨🇦 Toronto, Ontario, Canada

Site 601-102 (Part C); 🇨🇦 Québec, Quebec, Canada

Site 601-105 (Part C); 🇨🇦 Québec, Quebec, Canada