study to assess the safety, tolerability, pharmacokinetics and immunogenicity of ak006 in healthy subjects and subjects with chronic spontaneous urticaria

Conditions: Healthy Participants; Chronic Spontaneous Urticaria

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