Phase 1b Study to Assess the Safety and Tolerability of SR-878 in Patients With Rheumatoid Arthritis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- SciRhom GmbH
- 入组人数
- 27
- 试验地点
- 4
- 主要终点
- Dose-limiting toxicities
研究概览
简要总结
SR-878 is a newly developed medicine that aims to treat autoimmune disorders. It inhibits a protein (iRhom2), that regulates enzymes that are involved in the production of cytokines (small proteins that are crucial in controlling the activity of immune system cells). The aim of this clinical trial is to find a suitable safe and effective SR-878 dose for patients with rheumatoid arthritis. The study will include a screening period, an inpatient treatment period, and an outpatient follow-up period. The study duration for an individual participant is up to 113 days (about 16 weeks).
详细描述
Rationale: SR-878 is an investigational medicine that targets a specific protein, called iRhom2, which is involved in inflammation in autoimmune diseases like rheumatic arthritis (RA). SR 878 blocks multiple inflammatory pathways without affecting normal body functions such as skin and gut barrier protection. This could offer broader anti-inflammatory effects with fewer side effects compared to existing therapies that block only one pathway. In a previous study with healthy volunteers, SR-878 caused a temporary increase in inflammation markers in the blood. Because this was completely unexpected, the study was stopped early. However, animal studies showed that this reaction did not occur in animals already suffering from an inflammatory condition like RA. Therefore, this new study is testing SR-878 directly in RA patients, to see if it is safe and to find the right dose to use in future studies.
Main objective: To see if SR-878 is safe and well tolerated in RA patients and to find the safest effective dose.
Additional objectives: To understand how the drug is absorbed, distributed, and cleared from the body, assess blood biomarkers (markers that indicate how the drug acts in the body), monitor additional safety parameters, and whether the body develops any immune reaction to it.
Study endpoints: The main endpoints include the percentage of patients who experienced adverse events during the study, including serious events, events linked to SR-878, and events which were so severe that the treatment dose had to be reduced or stopped. Further endpoints assess how long the drug stays in the body, how much of it is present in the blood over time (up to Day 85 and beyond), and the highest level of the drug found in the blood by Day 85. The percentage of patients who have important changes in laboratory values, electrocardiograms (ECGs), and vital signs (blood pressure, pulse and temperature) will also be evaluated as well as changes in blood biomarkers. And finally, the percentage of patients who develop an immune reaction against SR-878 will be assessed.
Study design: The study consists of a screening period (up to 28 days prior to treatment), an inpatient treatment period (3 days), and a follow-up of 82 days, thus, each patient will be in the study for up to 113 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Men and women aged 18 to 60 years inclusive
- •Body weight ≥45 kg and body mass index ≤32 kg/m²
- •Diagnosis of RA according to the 2010 ACR/EULAR classification criteria, for at least 3 months before Screening
- •Stable dose of MTX for at least 4 weeks before Day 1
- •Ability to comply with the study protocol for the duration of the study, including inpatient confinement for about 3 days
- •Adequate venous access for blood collection
- •Women must not be pregnant or breastfeeding and
- •be of non-childbearing potential (postmenopausal [no menses for 12 months without an alternative medical cause] or surgically sterilized [documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy]) or
- •if of childbearing potential, must use a highly effective contraceptive method for the duration of the study and have a negative pregnancy test at Screening (blood test) Note: Acceptable highly effective methods of contraception include the intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion (must be documented); oral, intravaginal, transdermal, injectable, and implantable methods of hormonal contraception associated with inhibition of ovulation, vasectomized partner (must be documented); or sexual abstinence (only when it is the usual and preferred lifestyle of the participant)
- •Men must agree, from start of SR-878 administration until 90 days after SR-878 administration, to refrain from donating sperm and use a male condom when having sexual intercourse with a woman of childbearing potential, who is not currently pregnant, and advise her to use a highly effective contraceptive method
- •Disease status appropriate to be included in this exploratory safety study according to the investigator
排除标准
- •Abnormal findings in medical history and physical examination considered to be clinically relevant by the investigator
- •Clinically significant abnormal screening laboratory tests
- •Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, tuberculosis, and/or hepatitis C virus (HCV)
- •Clinically relevant ECG (12 leads) abnormalities
- •Acute infectious diseases within 2 weeks before Screening
- •History or presence of any autoimmune disease other than RA, chronic inflammatory condition, or clinically significant (in the opinion of the Investigator) atopic allergy (eg, asthma, urticaria, eczematous dermatitis, allergic rhinitis)
- •Relevant history of other renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, hematological, endocrine, inflammatory, chronic infectious, or neurological diseases
- •History of anaphylaxis to drugs or major allergic reactions in general, which in the view of the investigator may compromise the safety of the participant
- •Malignancy in the last 5 years before Screening (except basal or squamous cell skin cancer)
- •History of any chronic inflammatory arthritis with onset prior to the age of 18 or history of acute inflammatory joint disease of a different origin than RA
- •Current or previous (within 30 days or, if applicable, 5 half-lives of the investigational medicinal product (IMP), whatever is longer, before Screening) participation in another clinical study with an investigational drug and/or medical device
- •Known hypersensitivity to the active substance or to any of the excipients of the IMP and auxiliary medicinal products
- •Drug and alcohol abuse
- •Prohibited medication as outlined below
- •Plans to undergo elective procedures or surgeries at any time after signing the informed consent form until end of the study
- •Employees of the sponsor, or employees or relatives of the investigator
- •Individuals committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
- •Legal incapacity or limited legal capacity
研究组 & 干预措施
Verum
solution for infusion, administered intravenously
干预措施: SR-878 (Drug)
结局指标
主要结局
Dose-limiting toxicities
时间窗: Day 1 until day 85
The number of participants with dose-limiting toxicities (DLTs)
Maximum tolerated dose
时间窗: Day 1 until day 85
Determination of the maximum tolerated dose (MTD)
The number of participants with treatment-emergent adverse events (TEAEs), serious adverse events and related TEAEs
时间窗: Day 1 until day 85
Proportion of participants with treatment-emergent adverse events (TEAEs), serious adverse events and related TEAEs
dose-limiting toxicities
时间窗: Day 1 until day 85
The number of participants with dose-limiting toxicities (DLTs)
maximum tolerated dose
时间窗: Day 1 until day 85
Determination of the maximum tolerated dose (MTD)
次要结局
- To determine the proportion of participants with clinically relevant abnormal changes(Day 1 until day 85)
- To determine the pharmacokinetics (PK) as measured by t1/2(Day 1 until day 85)
- To determine the pharmacokinetics (PK) as measured by the area under the serum concentration-time curve (AUC0-85)(Day 1 to day 85)
- To determine the pharmacokinetics (PK) as measured by the area under the serum concentration- time curve (AUC0-inf).(Day 1 until day 85)
- To determine the pharmacokinetics (PK) as measured by the area under the serum concentration- time curve (AUC0-last).(Day 1 until day 85)
- To determine the pharmacokinetics (PK) as measured by Cmax.(Day 1 until day 85)
- To determine the pharmacokinetics (PK) as measured by tmax(Day 1 until day 85)
- To determine the pharmacokinetics (PK) as measured by the total CL(Day 1 until day 85)
- To determine the pharmacokinetics (PK) as measured by the Vz(Day 1 until day 85)
- To determine the pharmacokinetics (PK) as measured by t last(Day 1 until 85)
- Further safety assessments(Day 1 until day 85)