A Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding and Proof of Concept Study, to Assess the Efficacy, Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of Namilumab/MT203 at 4 Different Subcutaneous Doses - Together With an Open-Label, Dose-Escalated Extension to Assess Safety and Efficacy of One Year Treatment - in Subjects With Moderate to Severe Chronic Plaque Psoriasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 122
- 主要终点
- Percentage of Participants Achieving 75 Percent Reduction From Baseline Psoriasis Area and Severity Index (PASI) Score (PASI75 Response) at Week 12
研究概览
简要总结
The purpose of this study is to establish proof of efficacy for namilumab in moderate to severe plaque psoriasis, measured as Psoriasis Area and Severity Index (PASI)75 response rate at Week 12.
详细描述
The drug tested in this study is called namilumab. Namilumab was tested to prove its effectiveness in treating moderate to severe chronic plaque psoriasis. This study looked at improvement of plaque psoriasis in participants who take namilumab.
The study enrolled 122 participants. Participants were randomly assigned (by chance, like flipping a coin) to one of five treatment groups that were undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):
- Namilumab subcutaneous injection 300 mg Day 1, 150 mg Days 15, 43 and 71
- Namilumab subcutaneous injection 160 mg Day 1, 80 mg Days 15, 43 and 71
- Namilumab subcutaneous injection 100 mg Day 1, 50 mg Days 15, 43 and 71
- Namilumab subcutaneous injection 40 mg Day 1, 20 mg Days 15, 43 and 71
- Placebo (dummy inactive subcutaneous injection) - this is a liquid solution that looks like the study drug but has no active ingredient Days 1, 15, 43 and 71.
This study consisted of two parts. Eligible participants received 10 weeks of treatment with double-blinded study medication, followed by an extended treatment period (active extension period, intended to be 52 weeks) with open-label study medication. At Week 12, participants were assessed for primary endpoint response, which determined the course of their progression through the open-label treatment period. Participants who showed >=75% reduction of Baseline (Day 1) PASI at Week 12, "Responders", began a washout interval (for a maximum of 24 weeks) with no use of study medication: this interval continued until a partial (25%) loss of Week 12 treatment response is recorded in assessments conducted on a 2-weekly basis - thereby prompting the start of dosing with open-label (OL) study medication (Day 0 OL through Week 52 OL). In contrast, participants who did not show >=75% reduction of Baseline PASI score at Week 12, "Partial/Non-Responders", began the open-label extension period 4 weeks after the final dose of blinded study medication.
Participants were then followed-up through an 18-week post-treatment assessment period during which no medication was given. During the open-label extension period participants began dosing with 80 mg namilumab; however, if an inadequate treatment response was recorded, then dose escalation to 150 mg namilumab was implemented.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is male or female aged 18 to 70 years, inclusive.
- •Is suffering from active but clinically stable plaque psoriasis (for at least 6 months) involving >=10% of their body surface area and Psoriasis Area and Severity Index (PASI) score >=
- •Must have been a candidate for, or have received, >= phototherapy or systemic psoriasis therapy.
- •A male participant who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of the informed consent throughout the duration of the study (including the treatment period and 18 weeks after last dose of study medication).
- •A female participant of childbearing potential who is sexually active with a non-sterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study (including the treatment period and 18 weeks after last dose of study medication).
- •In the opinion of the investigator, is capable of understanding and complying with protocol requirements.
- •The participant or, when applicable, the participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.
排除标准
- •Has received any investigational agent during an interval equivalent to 5 half- lives for that agent agent - or an interval of 30 days if longer - prior to the study Baseline clinic visit, or is participating / plans to participate in any other clinical trial during this study.
- •Has received namilumab, any other Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) / GM-CSF receptor or granulocyte stimulating factor (G-GSF) signaling inhibitor either in a previous clinical study or as a therapeutic agent.
- •Is required to take excluded medications.
- •Has a history of hypersensitivity or allergies to namilumab or any of the contents of the formulation.
- •Has other forms of psoriasis (eg drug-induced psoriasis, pustular, erythrodermic, exfoliative, inverse and/or guttate psoriasis).
- •Evidence of skin conditions other than psoriasis (eg, eczema) at the time of the Screening clinic visit, or between the Screening visit and study drug initiation, that would interfere with evaluations of the effect of investigational product on psoriasis.
- •Has a history or evidence of a clinically significant disorder (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric), condition or disease that, in the opinion of the investigator and Takeda physician would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.
- •Evidence of clinically uncontrolled respiratory disease (including sarcoidosis) on the basis of data from the subjects' respiratory assessments - including chest X-ray, lung function tests (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], peak expiratory flow rate [PEFR]) and pulse oximetry performed at Screening. The subjects must have saturation of peripheral oxygen (SpO2) ≥ 94%, FEV1 and/or FVC ≥ 60 % of predicted values at Screening and Baseline and no uncontrolled lung disease. Subject treatment initiated or modified to control lung disease within 24 weeks prior to Screening must be considered exclusionary.
- •History of clinically significant interstitial lung disease - e.g. chronic or recurrent pulmonary infection where macrophages are important for the clearance of the infection (such as Pneumocystis (carinii) jiroveci pneumonia, allergic bronchopulmonary aspergillosis, Nocardia infections, Actinomyces infection).
- •Presence or history of active tuberculosis (TB) or latent TB infection, where no anti-TB treatment has been given or where successful completion of an appropriate course of anti-TB therapy cannot be documented.
- •A positive QuantiFERON-TB Gold test and / or evidence of active or latent TB by chest X- ray, not accompanied by initiation of an approved regimen of anti-TB therapy at least 12 months prior to the Baseline clinic visit.
- •Has a history of severe chronic obstructive pulmonary disease (COPD) and / or history of severe COPD exacerbation(s), or a history of asthma with exacerbations requiring hospitalization, within the last 12 months prior to the Screening visit.
- •History of methotrexate treatment-associated lung toxicity.
- •Has a history of cancer within the last 10 years except for adequately managed basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.
- •Has a history of treatment with anti-cancer chemotherapy (e.g. alkylating agents, anti-metabolites, purine analogues) and/or monoclonal antibodies, or has received GM-CSF / G-CSF treatment associated with chemotherapy within the last 5 years.
- •Has an underlying condition that predisposes to infections (eg immunodeficiency, history of poorly controlled diabetes, splenectomy).
- •Has any clinically significant illness within 4 weeks prior to the first dose of study medication or during the study - including acute or chronic infectious disease, which may influence the outcome of the study.
- •Has a known history of infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV), or has serological findings at the Screening visit which indicate active or latent hepatitis B, hepatitis C or HIV infection.
- •Has, in the judgment of the investigator, clinically significant abnormal clinical laboratory parameters at Screening including, but not limited to: Hemoglobin <8.5 g/dL, Neutrophils <1500/mm^3, Platelet count <75 000 cells/mm^3 and AST or ALT >2 x ULN.
- •Has a history of drug abuse (defined as any illicit drug use), or a history of alcohol abuse within 2 years prior to the Screening visit.
- •Any other condition that, in the judgment of the investigator, might cause this study to be detrimental to the participant's health.
- •If female, is (a) pregnant / lactating / intending to become pregnant before or within the period of 18 weeks immediately after receiving the last dose of study medication; (b) intending to donate ova during this time period.
- •Intends to donate sperm during the course of this study or within a period of 18 weeks after receiving the last dose of study medication.
- •Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee involved in conduct of this study (eg, spouse, parent, child, sibling), or may consent under duress.
研究组 & 干预措施
Blinded period: Namilumab 300 mg + namilumab 150 mg
Namilumab 300 mg (2 separate injections of 150 mg), subcutaneous injection, on Day 1, followed by namilumab 150 mg subcutaneous injection, on Days 15, 43 and 71.
干预措施: Namilumab (Drug)
Blinded period: Namilumab 160 mg + namilumab 80 mg
Namilumab 160 mg (2 separate injections of 80 mg), subcutaneous injection, on Day 1, followed by namilumab 80 mg subcutaneous injection, on Days 15, 43 and 71.
干预措施: Namilumab (Drug)
Blinded period: Namilumab 100 mg + namilumab 50 mg
Namilumab 100 mg (2 separate injections of 50 mg), subcutaneous injection, on Day 1, followed by namilumab 50 mg subcutaneous injection, on Days 15, 43 and 71.
干预措施: Namilumab (Drug)
Blinded period: Namilumab 40 mg + namilumab 20 mg
Namilumab 40 mg (2 separate injections of 20 mg), subcutaneous injection, on Day 1, followed by namilumab 20 mg subcutaneous injection, on Days 15, 43 and 71.
干预措施: Namilumab (Drug)
Blinded period: Placebo
Placebo (2 separate injections), subcutaneous injection, on Day 1, followed by placebo, subcutaneous injection, on Days 15, 43 and 71.
干预措施: Placebo (Drug)
Open label: Namilumab 80 mg
Namilumab 80 mg subcutaneous injection, at Week 0 and every 4 weeks thereafter up to 52 weeks (active extension period) - if appropriate on the basis of treatment response.
干预措施: Namilumab (Drug)
Open label: Namilumab 150 mg
Namilumab 150 mg, subcutaneous injection, from Week 8 and then every 4 weeks thereafter up to 52 weeks (active extension period) - if appropriate on the basis of treatment response.
干预措施: Namilumab (Drug)
结局指标
主要结局
Percentage of Participants Achieving 75 Percent Reduction From Baseline Psoriasis Area and Severity Index (PASI) Score (PASI75 Response) at Week 12
时间窗: Week 12
PASI is an assessment of psoriasis lesion severity and affected body area combined into single score. The body was divided into 4 sections: head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent body surface area (A) involved was estimated: 0= No involvement to 6= 90-100 percent (%). Severity was estimated by clinical signs: erythema (E), induration (I), and desquamation (D); scale: 0= no symptoms to 4= very marked. Final PASI = 0.1(Eh + Ih + Dh)Ah + 0.3(Et + It + Dt)At + 0.2(Eu + Iu + Du)Au + 0.4(El + Il + Dl)Al where head: 0.1, upper extremities (arms): 0.2, trunk: 0.3, lower extremities (legs): 0.4 (corresponding to approximately 10%, 20%, 30%, and 40% of body surface area, respectively); total possible score range: 0= no disease to 72= maximal disease. Participants showing at least 75% reduction in PASI score relative to baseline PASI Score are reported.
次要结局
- Change From Baseline in PASI Score at Weeks 2, 4, 6, 10, and 12(Baseline, Weeks 2, 4, 6, 10, and 12)
- Change From Baseline in Affected Body Surface Area (BSA) at Weeks 2, 4, 6, 10, and 12(Baseline, Weeks 2, 4, 6, 10, and 12)
- Change From Baseline in Short Form 36 Health Survey (SF-36) at Week 12(Baseline, Week 12)
- Percentage of Participants Achieving 90 Percent Reduction From Baseline PASI Score (PASI90 Response) at Weeks 2, 4, 6, 10 and 12(Weeks 2, 4, 6, 10 and 12)
- Percentage of Participants Achieving Greater Than or Equal to (>=) 2 Point Improvement From Baseline in Static Physicians Global Assessment (sPGA) Score at Weeks 2, 4, 6, 10 and 12(Weeks 2, 4, 6, 10 and 12)
- Percentage of Participants Achieving 75 Percent Reduction From Baseline PASI Score (PASI75 Response) at Weeks 2, 4, 6, and 10(Weeks 2, 4, 6 and 10)
- Change From Baseline in sPGA Score at Weeks 2, 4, 6, 10, and 12(Baseline, Weeks 2, 4, 6, 10, and 12)
- Percentage of Participants Achieving 50 Percent Reduction From Baseline PASI Score (PASI50 Response) at Weeks 2, 4, 6, 10 and 12(Weeks 2, 4, 6, 10 and 12)
- Change From Baseline in VAS Morning Stiffness Score at Weeks 2, 4, 6, 10, and 12(Baseline, Weeks 2, 4, 6, 10, and 12)
- Change From Baseline in Duration of Morning Stiffness at Weeks 2, 4, 6, 10, and 12(Baseline, Weeks 2, 4, 6, 10, and 12)
- Change From Baseline in Visual Analogue Scale (VAS) Itching Score at Weeks 2, 4, 6, 10, and 12(Baseline, Weeks 2, 4, 6, 10, and 12)
- Change From Baseline in EQ-5D-VAS Score at Week 12(Baseline, Week 12)
- Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score at Weeks 2, 4, 6, 10, and 12(Baseline, Weeks 2, 4, 6, 10, and 12)
- Percentage of Participants Achieving a sPGA Response of Clear (0) or Almost Clear (1) at Weeks 2, 4, 6, 10 and 12(Weeks 2, 4, 6, 10 and 12)
- Change From Baseline in VAS Joint Pain Score at Weeks 2, 4, 6, 10, and 12(Baseline, Weeks 2, 4, 6, 10, and 12)
- Change From Baseline in EuroQoL Health Questionnaire (EQ-5D)- Index Score at Week 12(Baseline, Week 12)
- Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 12(Baseline, Week 12)