An Exploratory Proof of Concept Study to Assess the Pharmacokinetics/Pharmacodynamics (PK/PD) of Nemolizumab in Adult Participants With Chronic Pruritus of Unknown Origin (CPUO)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Galderma R&D
- 入组人数
- 50
- 试验地点
- 52
- 主要终点
- Population Pharmacokinetics (PopPK) Model of the Elimination of nemolizumab During the 16-week Treatment Period Point
研究概览
简要总结
The primary objective of this study is to assess the PK/PD relationship of nemolizumab in adult participants aged 18 years or above with chronic pruritus of unknown origin (CPUO) during a 16-week treatment period.
详细描述
This study is to assess the PK/PD relationship of nemolizumab in adult participants with CPUO. The study will consist of a 2 to 4-week screening period, a 16-week treatment period, and an 8-week follow up period (12 weeks after last study drug injection). Participants will be randomized 4:1 to nemolizumab or placebo. Dosing will be adjusted according to participants body weight ( less than [<] 90 kilograms [kg] versus >= 90 kg). Participation in the study will last up to 28 weeks.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Participant must be 18 years of age or older.
- •Participants with chronic pruritus on normal-appearing skin (except for dry skin or excoriations) for at least 6 months before the screening visit.
- •Chronic pruritus considered of unknown origin (i.e., without a clear association to another condition or medication) as assessed by the investigator at baseline.
- •The pruritus must affect at least 4 of the following body areas: left lower limb, right lower limb, left upper limb, right upper limb, anterior trunk, posterior trunk.
- •History of insufficient control of the chronic pruritus with prior treatment.
- •Peak Pruritus Numeric Rating Scale (PP NRS) score greater than and equal to (>=) 7 in the 24-hour period prior to the Screening visit.
- •Weekly average Peak Pruritus Numeric Rating Scale (PP NRS) score >= 7 in the week (7 days) immediately prior to randomization, as recorded in the patient diary.
- •Female of childbearing potential must agree to use at least 1 adequate and approved method of contraception throughout the study and for 12 weeks after the last study intervention injection.
- •Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Females of non-childbearing potential must meet 1 of the following criteria:
- •Absence of menstrual bleeding for 1 year prior to screening without any other medical reason, confirmed with follicle stimulating hormone (FSH) level in the postmenopausal range
- •Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before screening
- •Signed informed consent.
- •Participant is willing and able to comply with all of the time commitments and procedural requirements of the clinical study protocol.
排除标准
- •Participants are excluded from the study if any of the following criteria apply :
- •Medical Conditions
- •Known dermatologic, systemic, neurologic or psychiatric condition(s), other than dry skin, that considered by the investigator to be the primary cause of current pruritus.
- •Documented parasitic infection, including skin parasites such as scabies, within 12 weeks prior randomization.
- •Cutaneous infection within 1 week before the baseline visit, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before the baseline visit.
- •Diagnosis of chronic pruritus of neuropathic origin including but not limited to scalp dysesthesia, brachioradial pruritus, generalized neuropathic pruritus or chronic pruritus of psychogenic origin (pruritus associated with psychological disorders such as delusional parasitosis or Morgellons disease).
- •Any medical or psychological condition or any clinically relevant laboratory abnormalities that put the participant at significant risk.
- •History of bullous pemphigoid or positive bullous pemphigoid autoantibodies at screening.
- •History of mastocytosis or serum total tryptase greater than (>) 20 nanograms per milliliter (ng/ml) at screening.
- •Active tuberculosis (TB) or non-tuberculosis mycobacterial infection, or a history of incompletely treated TB.
- •Positive serology results Hepatitis B surface antigen or (HBsAg) or Antibody to Hepatitis B core antigen (HBcAb), Hepatitis C virus (HCV) antibody with positive confirmatory test for HCV (e.g., polymerase chain reaction [PCR]), or Human Immunodeficiency Virus [HIV] antibody) at the screening visit.
- •Known or suspected immunodeficiency.
- •Lymphoproliferative disease or malignancy within the last 5 years.
- •Presence of major psychiatric diagnosis, clinically significant dementia, intellectual impairment, or any medical condition or disability which, in the investigator's opinion, may confound the assessment of nemolizumab's safety or efficacy or interfere with the participant's ability to comply with protocol mandated activities.
- •Receipt of prohibited medications within the specified timeframe before the baseline visit
- •Previous participation in a clinical study with nemolizumab
- •Currently participating or participated in any other study of an investigational drug or device, within the past 8 weeks (or 5 half-lives of the investigational drug, whichever is longer) before the screening visit, or is in an exclusion period (if verifiable) from a previous study.
- •Body weight < 30 kg.
- •Prior treatment with commercially available nemolizmab
- •Hypersensitivity to the active substance (nemolizumab) or to any of the excipients of the study intervention.
- •Requiring rescue therapy for pruritus during the screening period.
- •Alcohol or substance abuse within 6 months of the screening visit.
- •Planned or anticipated major surgical procedure or other activity that would interfere with the participant's ability to comply with protocol-mandated assessments.
- •Pregnant or breastfeeding female, or female planning a pregnancy during the study.
- •Vulnerable participant as defined by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP).
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Placebo
Participants weighing < 90 kg will receive two SC injections of matching placebo at baseline followed by 1 SC injection Q4W at Weeks 4, 8 and 12. Participants weighing >= 90 kg will receive two SC injections of matching placebo at baseline and at Weeks 4, 8, and 12.
干预措施: Placebo (Drug)
nemolizumab
Participants weighing < 90 kg will receive one subcutaneous (SC) injection of 30 milligrams (mg) nemolizumab (with 60 mg loading dose at baseline) every 4 weeks (Q4W) at Weeks 4, 8, and 12. Participants weighing >= 90 kg will receive two SC injections of 30 mg nemolizumab ( 60 mg total) at baseline (without loading dose) and at Weeks 4, 8, and 12.
干预措施: nemolizumab (Drug)
结局指标
主要结局
Population Pharmacokinetics (PopPK) Model of the Elimination of nemolizumab During the 16-week Treatment Period Point
时间窗: From Baseline up to Week 16
Point Estimate of Population Total Clearance (Cl/F) of nemolizumab will be reported.
Population Pharmacokinetics (PopPK) Model of the Distribution of nemolizumab During the 16-week Treatment Period Point
时间窗: From Baseline up to Week 16
Point Estimate of Population Volume of Distribution (Vd/F) of nemolizumab will be reported.
Population Pharmacokinetics (PopPK) Model of the Absorption of nemolizumab During the 16-week Treatment Period Point
时间窗: From Baseline up to Week 16
Point Estimate of Absorption Rate Constant (Ka) of nemolizumab will be reported.
Population Pharmacokinetics (PopPK) Model of the Elimination of nemolizumab During the 16-week Treatment Period Point
时间窗: From Baseline up to Week 16
Point Estimate of Population Total Clearance (Cl/F) of nemolizumab will be reported.
Population Pharmacokinetics (PopPK) Model of the Distribution of nemolizumab During the 16-week Treatment Period Point
时间窗: From Baseline up to Week 16
Point Estimate of Population Volume of Distribution (Vd/F) of nemolizumab will be reported.
Population Pharmacokinetics (PopPK) Model of the Absorption of nemolizumab During the 16-week Treatment Period Point
时间窗: From Baseline up to Week 16
Point Estimate of Absorption Rate Constant (Ka) of nemolizumab will be reported.
Pharmacokinetic (PK)/Pharmacodynamic (PD) Model of the Effect of nemolizumab Systemic Exposure on Pruritus during 16-week Treatment Period
时间窗: From Baseline up to Week 16
Point Estimate of population IC50 of nemolizumab, i.e. the drug concentration required to produce 50% of the maximal inhibition of Average Peak Pruritus, will be reported.
次要结局
- Number of Participants With Adverse Events (AEs), Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs), AEs Leading to Study Intervention Withdrawal, AEs Leading to Study Discontinuation(From start of study up to follow-up period (Week 24))
- Individual Maximum Serum Concentration (Cmax) of nemolizumab(From Baseline up to Week 16)
- Individual Time to Reach Maximum Serum Concentration (Tmax) of nemolizumab(From Baseline up to Week 16)
- Individual Area Under the Concentration-time Curve Within a Dosing Interval (AUCtau) of nemolizumab(From Baseline up to Week 16)
- Terminal Half-life (t1/2) of nemolizumab(From Baseline up to Week 16)
- Individual Observed Ctrough Concentrations of nemolizumab(Week 16)
- Individual Model - derived Ctrough Concentrations of nemolizumab(Week 16)
- Individual Total Clearance (Cl/F) of nemolizumab(From Baseline up to Week 16)
- Individual Volume of Distribution (Vd/F) of nemolizumab(From Baseline up to Week 16)
- Individual Absorption Rate Constant (Ka) of nemolizumab(From Baseline up to Week 16)
- Individual Maximum Serum Concentration (Cmax) of nemolizumab(From Baseline up to Week 16)
- Individual Time to Reach Maximum Serum Concentration (Tmax) of nemolizumab(From Baseline up to Week 16)
- Individual Area Under the Concentration-time Curve Within a Dosing Interval (AUCtau) of nemolizumab(From Baseline up to Week 16)
- Terminal Half-life (t1/2) of nemolizumab(From Baseline up to Week 16)
- Change From Baseline in Weekly Average Peak Pruritus Numeric Rating Scale (PP NRS)(Up to Week 16)
- Number of Participants With Adverse Events (AEs), Treatment Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs), AEs Leading to Study Intervention Withdrawal, AEs Leading to Study Discontinuation(From start of study up to follow-up period (Week 24))