Chronic Spontaneous Urticaria, Healthy Participants
Conditions
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.
Interventions
DRUGAK006-IV
Intravenous infusion
DRUGPlacebo-IV
Intravenous infusion
DRUGAK006-SC
Subcutaneous
DRUGPlacebo-SC
Subcutaneous
Sponsors
Allakos Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind (placebo) essentially identical in appearance to the investigational drug (AK006)
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 |
| AK006 serum concentrations | Up to Day 141 (Part A, B, D); Up to Day 197 (Part C) | AK006 ng/mL |
| 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) |
Countries
Canada, United States
Outcome results
None listed