NCT07597668进行中（未招募）1 期
A Multicentre, Double-blind, Randomised, Comparative Pharmacokinetics, Pharmacodynamics, Safety, and Immunogenicity Study of RPH-035 Versus Ocrevus® in Patients With Relapsing-remitting or Secondary Progressive Multiple Sclerosis With Exacerbations
R-Pharm23 个研究点 分布在 1 个国家目标入组 180 人开始时间: 2025年4月16日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 180
- 试验地点
- 23
- 主要终点
- The area under the concentration-time pharmacokinetic curve (AUC (14-169 days)) of ocrelizumab
研究概览
简要总结
The study goal is to establish the equivalence of pharmacokinetic (PK) properties, as well as the comparability of safety, immunogenicity (IG) and pharmacodynamics (PD) of the drug product RPH-035 (R-Pharm JSC, Russia) in comparison with the drug product Ocrevus® (F. Hoffmann-La Roche Ltd., Switzerland) when used in patients with multiple sclerosis (MS)
详细描述
This study is a multicentre, double-blind, randomised, comparative Phase I study
The clinical study includes the following periods:
- Screening period: days [-27…-0] (up to 1st administration of study therapy)
- Main period: weeks [1-49]
Patients who meet the eligibility criteria shall be randomised in a 1: 1 ratio to one of two study arms: RPH-035 and Ocrevus®
During the Main Period, the patients will receive their first infusion of ocrelizumab (RPH-035 or Ocrevus®) at a dose of 300 mg, followed by another 300 mg of the drug product after 2 weeks. The duration of ocrelizumab administration will be 2.5 hours ± 15 minutes. The third infusion at a dose of 600 mg should be administered 6 months after the first infusion of the initial dose. The administration is scheduled for the "Week 25" visit.
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)
盲法说明
This clinical study is a double-blind study by design. Neither the investigator nor the patient will know which drug product (RPH-035 or Ocrevus®) is administered to the patient until week 49 of the study
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients shall meet all of the following inclusion criteria:
- •Availability of the voluntarily signed and dated patient Informed Consent (IC) form for participation in this study
- •Multiple sclerosis with exacerbations (relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS) with exacerbations) according to the McDonald diagnostic criteria as revised in 2017, with symptoms lasting at least 1 year before signing the IC form
- •The patient's medical history includes the use of ≤ 3 prior multiple sclerosis disease modifying drugs (DMT)
- •The patient has one of the following signs of disease activity:
- •≥ 2 documented disease exacerbations in the previous 24 months before the IC signing date
- •≥ 1 documented disease exacerbation in the previous 12 months before the IC signing date
- •1 documented exacerbation in the previous 24 months before the IC signing date and ≥ 1 documented brain lesion on the contrast-enhanced Magnetic Resonance Imaging (MRI) scan in the previous 6 months before the IC signing date
- •Expanded Disability Status Scale (EDSS) index is 0-5.5 points inclusively on screening
- •No Multiple sclerosis (MS) exacerbations within 30 days before the IC signing date and throughout the entire screening examination
- •Ability, in the Investigator's opinion, to comply with the Protocol procedures and requirements
- •Negative pregnancy test for female participants with preserved reproductive potential
- •Consent of the patient with preserved reproductive potential to abstain from heterosexual contacts or to use reliable contraceptive methods, starting from the moment of the IC form signing, throughout the entire treatment period within the study, as well as for 12 months after the last ocrelizumab administration. Female participants are considered infertile if definitive amenorrhea was determined (from patient's words) retrospectively after 12 months of natural amenorrhea, i.e amenorrhea with an appropriate clinical status, such as a suitable age (between 45 and 55 years )
- •Patients cannot be included in the study if they meet at least one of the following
排除标准
- •Medical history of hypersensitivity to monoclonal antibody drugs or to any component of the investigational medicinal products
- •Prior therapy with ocrelizumab
- •Primary progressive multiple sclerosis or SPMS without exacerbations
- •Contraindications for MRI, including intolerance to Gd-containing contrast agents and claustrophobia
- •Medical history of other neurological diseases (excluding migraines) or first diagnosed on screening, including but not limited to the following:
- •ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or spinal cord ischemia
- •malignant and benign central nervous system (CNS) tumours (meningiomas, gliomas, etc.) requiring surgical intervention
- •potential metabolic causes of myelopathy, identified from the medical history or in patient words (untreated vitamin B12 deficiency, etc.)
- •infectious myelopathy (syphilis, Lyme disease, human T-lymphotropic virus 1 [HTLV-1], herpes zoster)
- •hereditary progressive CNS degenerative disorder, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke)
- •neuromyelitis optical spectrum disorders
- •progressive multifocal leukoencephalopathy
- •Systemic autoimmune disease (lupus, rheumatoid arthritis, antiphospholipid antibody syndrome, Sjorgen's syndrome, Behcet's syndrome)
- •Sarcoidosis
- •Medical history of severe, clinically significant brain or spinal cord injury (brain contusion, spinal cord compression)
- •Medical history of the patient includes the following therapy:
- •targeted biological B-cell therapy (ocrelizumab, rituximab or ofatumumab, etc.)
- •bone marrow transplantation, lymphocyte irradiation
- •any unregistered biological drug product for MS treatment
- •The patient received any of the following therapies (subject to the time/dose restrictions specified):
- •natalizumab (inclusion of such patients in the study is allowed, provided that the therapy was completed > 12 months before the IC signing date)
- •fampridine (administration is allowed, provided only that the patient has been receiving continuous therapy with the drug product for at least 3 months before the IC signing date)
- •alemtuzumab (< 4 years before the IC signing date)
- •fingolimod (< 6 weeks before the IC signing date)
- •dimethyl fumarate, siponimod (< 4 before the IC signing date)
- •teriflunomide (< 3.5 months before the IC signing date), in case of accelerated elimination procedure < 2 weeks before the IC signing date)
- •immunosuppressive drug products: azathioprine, mycophenolate mofetil, methotrexate, TNF-α inhibitors (< 6 months before the IC signing date) cyclophosphamide, mitoxantrone, cladribine (< 24 months before the IC signing date)
- •interferon beta/glatiramer acetate (< 2 weeks before the IC signing date)
- •immunoglobulin intravenous administration within < 12 weeks before the IC signing date
- •plasmapheresis or plasma adsorption (< 21 days before the randomisation date)
- •therapy with systemic glucocorticosteroids (GCS), adrenocorticotropic hormones (ACTH) < 1 month before MRI screening
- •live or live attenuated vaccine within < 3 months before the IC signing date or vaccination plans for the study period
- •Concomitant diseases that increase the patient's risk of AE development during the use of the investigational therapy or may affect the assessment of MS symptoms severity; mask, intensify, modify MS symptoms or cause clinical and laboratory-instrumental symptoms similar to those in MS as confirmed by primary documentation data:
- •uncontrolled arterial hypertension characterised by systolic blood pressure (BP) above 150 mmHg or diastolic BP above 90 mmHg during the antihypertensive therapy
- •medical history of moderate or severe heart failure (functional class III/IV according to the New York Heart Association (NYHA) classification), stable effort angina of functional class III-IV, unstable effort angina, or medical history of myocardial infarction less than 6 months before randomisation
- •diagnosis of any clinically significant (in the opinion of the investigator) respiratory disease including, but not limited to, chronic obstructive pulmonary disease of grade 3 or 4 severity
- •diagnosis of active liver disease or liver failure based on medical history
- •Haematological disorders:
- •haemoglobin < 80 g/L
- •white blood cells (WBC) < 3.0 × 10^9/L
- •absolute neutrophil count < 1.5 × 10^9/L
- •absolute lymphocyte count < 0.5 × 10^9/L
- •platelets < 100 × 10^9/L
- •Renal impairment:
- •a. creatinine > 1.5 × upper limit of normal (ULN) or glomerular filtration rate < 45 mL/min, calculated using CKD-EPI formula
- •Hepatic impairment:
- •a. bilirubin, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 2 × ULN
- •Presence of oncological pathology that is progressing or requires anti-tumour therapy (including hormonal therapy) within 5 years before the IC signing date, except for radically resected cervical carcinoma in situ or radically resected basal cell/squamous-cell carcinoma of skin
- •Medical history of diverticulitis or other gastrointestinal tract (GI) disorders (e.g., inflammatory bowel disease, mechanical ileus, hernia) that can cause gastrointestinal (GI) perforations in patients
- •Diseases (e.g., asthma, psoriasis) that require treatment with immunosuppressive biological drugs or systemic corticosteroids during the study
- 另有 18 项未显示
研究组 & 干预措施
Ocrevus®
Active Comparator
During the Main Period, the patients receive their first infusion of ocrelizumab (Ocrevus®) at a dose of 300 mg, followed by another 300 mg of the drug product after 2 weeks. The duration of ocrelizumab administration is 2.5 hours ± 15 minutes. The third infusion at a dose of 600 mg is administered 6 months after the first infusion of the initial dose
Premedication is mandatory and is carried out according to the following scheme:
- methylprednisolone at a dose of 100 mg (or dexamethasone at a dose of 18.8 mg, or an equivalent drug product) intravenously 30 ± 10 minutes before the start of each infusion
- antihistamine drug (e.g., diphenhydramine, suprastin, or an equivalent drug product) 30-60 minutes before the start of each infusion
- antipyretic drug (e.g., paracetamol) 30-60 minutes before the start of each infusion
干预措施: Ocrevus® (Drug)
RPH-035
Experimental
During the Main Period, the patients receive their first infusion of ocrelizumab (RPH-035) at a dose of 300 mg, followed by another 300 mg of the drug product after 2 weeks. The duration of ocrelizumab administration is 2.5 hours ± 15 minutes. The third infusion at a dose of 600 mg is administered 6 months after the first infusion of the initial dose
During the After-Therapy Period, patients will receive an IV infusion of 600 mg of ocrelizumab (RPH-035) at weeks 49, 73, and 97
Premedication is mandatory and is carried out according to the following scheme:
- methylprednisolone at a dose of 100 mg (or dexamethasone at a dose of 18.8 mg, or an equivalent drug product) intravenously 30 ± 10 minutes before the start of each infusion
- antihistamine drug (e.g., diphenhydramine, suprastin, or an equivalent drug product) 30-60 minutes before the start of each infusion
- antipyretic drug (e.g., paracetamol) 30-60 minutes before the start of each infusion
干预措施: RPH-035 (Drug)
结局指标
主要结局
The area under the concentration-time pharmacokinetic curve (AUC (14-169 days)) of ocrelizumab
时间窗: Day 14 to Day 169
The area under the concentration-time pharmacokinetic curve of ocrelizumab after the second (single) administration, truncated at Day 169 (AUC (14-169 days))
次要结局
- The area under the concentration-time pharmacokinetic curve (AUC (0-14 days)) of ocrelizumab(Up to Day 14)
- Maximum serum concentration of ocrelizumab after the first administration (Cmax (0-14 days))(Up to Day 14)
- Maximum serum concentration of ocrelizumab after the second administration (Cmax (14-169 days))(Day 14 to Day 169)
- Percentage of patients with adverse reactions (ARs) of any severity(Up to Day 337)
- Percentage of patients with adverse events (AEs) of any severity(Up to Day 337)
- Percentage of patients with AEs of severity grade ≥ 3(Up to Day 337)
- Percentage of patients with ARs of severity grade ≥ 3(Up to Day 337)
- Percentage of patients with serious adverse events (SAEs)(Up to Day 337)
- Percentage of patients with serious adverse reactions (SARs)(Up to day 337)
- Percentage of patients who required discontinuation of therapy due to adverse events/adverse reactions (AEs/ARs)(Up to Day 337)
- Binding anti-drug antibodies (ADA) to ocrelizumab over a period of up to 24 weeks from the start of the therapy(Up to Day 169)
- Binding anti-drug antibodies (ADA) to ocrelizumab over a period of up to 48 weeks from the start of the therapy(Up to Day 337)
- Neutralizing antibodies (nAB) to ocrelizumab over a period of up to 24 weeks from the start of therapy(Up to Day 169)
- Neutralizing antibodies (nAB) to ocrelizumab over a period of up to 48 weeks from the start of therapy(Up to Day 337)
研究者
研究点 (23)
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