A Phase I, Partially-randomised, Partially Double-blinded, Safety, Tolerability and Pharmacokinetic Study of ABY-035 in Healthy Subjects and Psoriasis Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 4
- 主要终点
- Number of Participants With Abnormal Laboratory Values or other Adverse Events
研究概览
简要总结
The purpose of this first-in-human study is to investigate the safety and tolerability of ABY-035 when administered intravenously and subcutaneously, to healthy volunteers and to psoriasis patients.
详细描述
This first in human study with ABY-035 (a novel IL-17A inhibitor (interleukin 17A)) consists of four Parts. Part A consists of a single ascending intravenous dose study with 40 healthy volunteers divided into five dose cohorts. Each group consists of 8 subjects where 6 subjects will receive ABY-035 and 2 will receive placebo. The subjects will be followed for pharmacokinetic and safety assessments up to Day 95 after dosing.
Part B of the study consists of 6 healthy volunteers who will be given a single subcutaneous dose of ABY-035. The subjects will follow the same study visit schedule as Part A.
Part C of the study will include up to 12 moderate-to-severe psoriasis patients who each patient will be given a single intravenous dose of ABY-035. The patients will follow the same study visit schedule as Part A and B.
Part D of the study will include up to 18 psoriasis patients (mild, moderate or severe). Each patient will participate in 3 or 7 biweekly dosing occasions of subcutaneously administered ABY-035. Patients will be followed regularly for safety, efficacy and pharmacokinetics for 8 weeks post-final dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part A, Part B
- •Males or females between 18 and 65 years of age
- •Body mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2, inclusive. maximum body weight of 120 kg
- •In good health, as determined by medical history, physical examination, vital signs assessment, 12 lead electrocardiogram (ECG) and clinical laboratory evaluations.
- •Subjects will have given their written informed consent to participate in the study
- •In addition for Part C and D
- •Males or females between 18 and 65 years of age
- •Body mass index (BMI) between 18.0 kg/m2 and 39.9 kg/m2, inclusive. Minimum body weight of 45 kg
- •Part C: Patients must have had a diagnosis of moderate to severe plaque type psoriasis at least 6 months prior to administration of the study drug without a documented flare within 30 days prior to Screening. Patients with concurrent psoriatic arthritis may be enrolled.
- •Part D: Patients must have had a diagnosis of plaque type psoriasis (mild, moderate or severe) at least 6 months prior to administration of the study drug without a documented flare within 30 days prior to Screening. Patients with concurrent psoriatic arthritis may be enrolled.
- •Part C: Have plaque type psoriasis covering at least 10% of total body surface area (BSA) at Screening and at Baseline (Day 1) and have a PASI score of 12 or greater at Screening and at Baseline (Day 1).
- •Part D: Have at least one psoriatic lesion
- •Exclusion criteria:
- •Part A, Part B, Part C and Part D
- •Subjects who have any clinically significant medical history, as determined by the investigator
- •Subjects who smoke more than 15 cigarettes, or equivalent, per day
- •Alcohol and/or drug abuse
- •Positive for HIV, Hepatitis B, Hepatitis C, or tuberculosis
- •Subjects who have received a live vaccination within the 3 months prior to Screening
- •Subjects who are pregnant or lactating
- •Subjects who do not agree to use appropriate contraception
- •Subjects who have a history of anaphylaxis, drug allergy or clinically significant allergic condition (excluding non active hayfever)
- •Participation in another clinical trial
- •Subjects who, in the opinion of the investigator, should not participate in this study
- •In addition for Part C and D
- •Patients who currently have non plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular)
- •Patients who have current drug induced psoriasis
- •Have any history of any use of or have participated in clinical trials for any therapeutic agent directly targeted to any IL 17 cytokine or receptor
- •Have received phototherapy within 4 weeks prior to Day 1
- •Patients who have received systemic medications or treatments that could affect psoriasis or PASI evaluation (including, but not limited to, oral or injectable corticosteroids, retinoids, 1,25 dihydroxy vitamin D3 and analogues, fumaric acid esters, psoralens, anti TNF (tumour necrosis factor) biologics, anti IL 12/23 biologics, or herbal treatments), within 5 half lives prior to Day 1 (4 weeks for oral anti psoriatics, 12 weeks for psoralens and PUVA (oral psoralen with ultraviolet A), and 24 weeks for biologics)
- •Patients who have used topical medications and treatments that could affect psoriasis or PASI evaluation (eg, corticosteroids, coal tar, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, and trimethyl psoralens) within 2 weeks of administration of IMP (Investigational Medicinal Product)
- •Patients who have used any systemic immunosuppressants (eg, methotrexate, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, or tacrolimus) within 8 weeks of administration of IMP (or 5 half lives, whichever is longer).
排除标准
- 未提供
研究组 & 干预措施
ABY-035 i.v.
Part A: SAD (single ascending dose) including five different dose cohorts. ABY-035 given as intravenous injections. 6 ABY-035 and 2 placebo in each cohort.
干预措施: Placebo (Drug)
ABY-035 i.v.
Part A: SAD (single ascending dose) including five different dose cohorts. ABY-035 given as intravenous injections. 6 ABY-035 and 2 placebo in each cohort.
干预措施: ABY-035 i.v. (Drug)
ABY-035 s.c.
Part B: Bioavailability study where 6 subjects will receive ABY-035 as a single subcutaneous injection.
干预措施: ABY-035 s.c. (Drug)
ABY-035 i.v. in psoriasis patients
Part C: Up to 12 psoriasis patients will receive ABY-035 as a single intravenous injection.
干预措施: ABY-035 i.v. (Drug)
ABY-035 s.c. in psoriasis patients
Part D: Up to 18 patients will receive 3 or 7 biweekly doses of ABY-035 as s.c. injections
干预措施: ABY-035 s.c. (Drug)
结局指标
主要结局
Number of Participants With Abnormal Laboratory Values or other Adverse Events
时间窗: Follow-up visit (Day 141)
Safety is monitored by Vital signs, 12-lead ECGs, urinalysis, hematology, clinical chemistry, coagulation, proinflammatory cytokines and CRP
次要结局
- AUC (Area Under the Concentration-time curve) of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- t1/2 (half-life) of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- Maximum serum concentration (Cmax) of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- Time of maximum observed plasma concentration of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- Time immediately prior to first quantifiable concentration of ABY-035 following a single subcutaneous administration in healthy subjects.(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 71, Day 95)
- Time of last quantifiable plasma concentration of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- Mean Residence Time (MRT) of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- Total plasma clearance of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- Absolute bioavailability (F) of ABY-035 following a single subcutaneous administration in healthy subjects.(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 71, Day 95)
- Volume of distribution during the terminal elimination phase of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- Volume of distribution at steady state of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis through analysis of serum samples(Day 1, Day 2, Day 3, Day 4, Day 8, Day 15, Day 22, Day 29, Day 30, Day 31, Day 32, Day 43, Day 57, Day 71, Day 85, Day 95, Day 113, Day 141)
- Clinical efficacy of ABY-035, using PASI (Psoriasis Area and Disease Index) response, following single dose intravenous administration in patients with moderate-to-severe psoriasis.(Screening, Day -1, Day 2, Day 8, Day 15, Day 17, Day 22, Day 29, Day 31, Day 43, Day 71, Day 57, Day 85, Day 95, Day 113, Day 123, Day 141, Day 151)
- Immunogenicity of ABY-035 in healthy subjects and in patients with moderate-to-severe psoriasis(Day -1, Day 1, Day 15, Day 29, Day 57, Day 85, Day 95, Day 113, Day 141)