A Parallel-design Phase 1 Study to Assess Safety, Tolerability and Pharmacokinetics/Exposure Following Different Single Dose Levels of MOR106 (Administered Subcutaneously or Intravenously) in Healthy Male Subjects (Randomized, Open-label), and in Subjects With Moderate to Severe Atopic Dermatitis (Randomized, Placebo-controlled, Double-blind, Repeated Subcutaneous Dosing Over 12 Weeks)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Galapagos NV
- 入组人数
- 44
- 试验地点
- 15
- 主要终点
- The number of incidents of Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs) and discontinuations due to Adverse Events (AEs) Part 1.
研究概览
简要总结
The clinical study consists of three parts:
- Part 1 with healthy volunteers.
- Part 2 and Part 3 including subjects with moderate to severe atopic dermatitis (a skin disease).
For Part 1 the main goal of the study is to compare the safety, tolerability, and exposure of administration of the test drug via an injection in a skin layer just under the surface (subcutaneous), to administration of the test drug into the vein (intravenous).
For Part 2 and Part 3 the main goal of the study is to assess the safety and tolerability of administration of the test drug via an injection in a skin layer just under the surface (subcutaneous) during 12 weeks of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
Part 1 - randomized open label. Part 2 and Part 3 - randomized double blind.
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
- •Male between 18-50 years of age (extremes included), on the day of signing the informed consent form (ICF).
- •Subjects between 65-88 kg (extremes included) with a body mass index (BMI) between 18-30 kg/m², inclusive.
- •Judged to be in good health based upon the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and screening laboratory profile prior to the initial investigation medicinal product (IMP) administration.
- •Part 2 and Part 3:
- •Male or female between 18-65 years of age (extremes included), on the day of signing ICF.
- •A BMI between 18-30 kg/m², inclusive.
- •Diagnosis of AD for at least one year since first diagnosis as per Hanifin and Rajka Criteria.
- •EASI ≥ 12 at screening and ≥ 16 at the baseline visit (Day 1 predose)
- •≥ 10% BSA of AD involvement at screening.
- •IGA score ≥ 3 (on 0-4 IGA scale).
- •Willingness to use an additive free, basic, bland emollient twice daily for at least seven days before the baseline visit and throughout the study.
- •Subject is a candidate for systemic therapy and is not responding adequately or has a contraindication to topical corticosteroids (TCS) and / or topical calcineurin inhibitors (TCI), per investigator's judgment.
排除标准
- •Part 1, Part 2 and Part 3:
- •Known hypersensitivity to IMP ingredients as determined by the investigator (such as, but not limited to, anaphylaxis requiring hospitalization).
- •Prior treatment with MOR
- •Any concurrent illness, condition, disability, or clinically significant abnormality (including laboratory tests, ≥ New York Heart Association Classification (NYHA) III/IV) or clinically significant illness in the three months prior to initial IMP administration that, in the investigator's opinion, represents a safety risk for the subject's participation in the study, may affect the interpretation of clinical safety or efficacy data, or may prevent the subject from safely completing the assessments required by the protocol.
- •History of, or current immunosuppressive condition.
- •In addition for Part 2 and 3:
- •Active chronic or acute skin infection requiring treatment with systemic (oral, sc or iv) antibiotics, antivirals or antifungals within 4 weeks of baseline, or clinical signs of infective eczema within 1 week before baseline (Day 1 pre-dose).
- •Having used any of the following treatments:
- •i) Exposure to a biologic therapy for AD. ii) Immunosuppressive/ immunomodulating drugs (e.g. systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon-γ (IFN-γ), azathioprine, methotrexate, etc.) within 4 weeks of baseline. iii) Phototherapy (ultraviolet (UVB) or Psoralen Ultraviolet A [PUVA]) for AD within four weeks of baseline. iv) Treatment with TCS or TCI within two weeks before the baseline visit. v) Treatment with biologics (for non-AD indications) within five half-lives (if known) or 12 weeks prior to baseline visit, whichever is longer. vi) Regular use (more than two visits per week) of a tanning booth/parlor within four weeks of the screening visit.
研究组 & 干预措施
MOR106 Single Dose A, i.v. infusion, Part 1
A single dose of MOR106 will be administered by i.v. infusion.
干预措施: MOR106 (Drug)
MOR106 Single Dose B, s.c. injection, Part 1
A single dose of MOR106 will be administered by s.c. injection.
干预措施: MOR106 (Drug)
MOR106 Single Dose C, s.c. injection, Part 1
A single dose of MOR106 will be administered by s.c. injection.
干预措施: MOR106 (Drug)
MOR106 Single Dose D, s.c. injection, Part 1
A single dose of MOR106 will be administered by s.c. injection.
干预措施: MOR106 (Drug)
MOR106 Repeated Doses E, s.c. injection, Part 2
Repeated doses of MOR106 will be administered by s.c. injection with a loading dose on the first day of administration.
干预措施: MOR106 (Drug)
Placebo s.c.injection, Part 2
Corresponding Placebo will be administered by s.c. injection.
干预措施: Placebo (Drug)
MOR106 Repeated Doses F, s.c. injection, Part 3
Repeated doses of MOR106 will be administered by s.c. injection with a loading dose on the first day of administration.
干预措施: MOR106 (Drug)
Placebo s.c.injection, Part 3
Corresponding Placebo will be administered by s.c. injection.
干预措施: Placebo (Drug)
结局指标
主要结局
The number of incidents of Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs) and discontinuations due to Adverse Events (AEs) Part 1.
时间窗: From study drug administration until Day 50 postdose or early discontinuation (ED) visit
To evaluate the safety and tolerability of single doses of MOR106 administered s.c. in comparison to i.v.
The number of incidents of Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs) and discontinuations due to Adverse Events (AEs) Part 2.
时间窗: From study drug administration until Day 197 postdose or early discontinuation (ED) visit
To evaluate the safety and tolerability of multiple doses of MOR106 administered s.c.
The number of incidents of Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), serious adverse events (SAEs) and discontinuations due to Adverse Events (AEs) Part 3.
时间窗: From study drug administration until Day 155 postdose or early discontinuation (ED) visit
To evaluate the safety and tolerability of multiple doses of MOR106 administered s.c.
Terminal elimination half-life (t1/2) Part 1.
时间窗: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
To characterize the PK of MOR106.
AUC ratio between s.c. and i.v. dosing (area under the plasma concentration-time curve) Part 1.
时间窗: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
To determine the relative bioavailability following sc route of administration.
Area under the serum concentration-time curve from time zero to infinity (AUC0-inf) Part 1.
时间窗: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
To characterize the pharmacokinetics (PK) of MOR106.
Maximum observed plasma concentration (Cmax) Part 1.
时间窗: Between Day 1 study period and Day 50 postdose or early discontinuation (ED) visit
To characterize the PK of MOR106.
次要结局
- Percent change in Scoring Atopic Dermatitis (SCORAD) score Part 2.(From baseline to Day 85)
- Percent change in Scoring Atopic Dermatitis (SCORAD) score Part 3.(From baseline to Day 85)
- Absolute and percent change in body surface area (BSA), Patient Oriented Eczema Measure (POEM) score Part 2.(From baseline to Day 85)
- Absolute and percent change in body surface area (BSA), Patient Oriented Eczema Measure (POEM) score Part 3.(From baseline to Day 85)
- Occurrence of anti-drug antibodies (ADA) Part 1.(From baseline through Day 50 postdose or early discontinuation (ED) visit)
- Occurrence of anti-drug antibodies (ADA) Part 3.(From baseline through Day 155 postdose or early discontinuation (ED) visit)
- MOR106 serum concentrations after multiple s.c. administrations Part 2.(Between Day 1 study period and Day 197 postdose or early discontinuation (ED) visit)
- Percent change in Eczema Area and Severity Index (EASI) Part 2.(From baseline to Day 85)
- Percent change in Eczema Area and Severity Index (EASI) Part 3.(From baseline to Day 85)
- Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score Part 2.(From baseline to Day 85)
- Occurrence of anti-drug antibodies (ADA) Part 2.(From baseline through Day 197 postdose or early discontinuation (ED) visit)
- MOR106 serum concentrations after multiple s.c. administrations Part 3.(Between Day 1 study period and Day 155 postdose or early discontinuation (ED) visit)
- Proportion of subjects who achieve ≥50% overall improvement in Eczema Area and Severity Index (EASI) score Part 3.(From baseline to Day 85)
- Time to first response of Eczema Area and Severity Index (EASI) improvement with 50% Part 2.(From baseline to Day 85)
- Time to first response of Eczema Area and Severity Index (EASI) improvement with 50% Part 3.(From baseline to Day 85)
- Proportion of subjects who achieve ≥75% and ≥90% improvement in Eczema Area and Severity Index (EASI) Part 2.(From baseline to Day 85)
- Proportion of subjects who achieve ≥75% and ≥90% improvement in Eczema Area and Severity Index (EASI) Part 3.(From baseline to Day 85)
- Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1 Part 2.(at Day 85 visit)
- Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score of 0 or 1 Part 3.(at Day 85 visit)
- Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score reduction of ≥2 Part 2.(at Day 85 visit)
- Proportion of subjects who achieve an Investigators' Global Assessment (IGA) score reduction of ≥2 Part 3.(at Day 85 visit)
- Weekly change from baseline in Pruritus Numeric Rating Scale (NRS) Part 2.(From screening until Day 197 or early discontinuation (ED) visit twice daily)
- Weekly change from baseline in Pruritus Numeric Rating Scale (NRS) Part 3.(From screening until Day 155 or early discontinuation (ED) visit twice daily)