CLASP MS: The study evaluating the efficacy and safety of Polish cladribine in the treatment of patients with secondary progressive multiple sclerosis - a phase 2, randomized, double-blind, placebo-controlled trial.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 188
- 试验地点
- 2
- 主要终点
- Percent brain volume change from last cladribine dose (week 26) to end of study (week 122).
研究概览
简要总结
The aim of the study is to evaluate the efficacy and safety of subcutaneously administered cladribine compared with placebo in patients with secondary progressive multiple sclerosis (SPMS) who have had progression in the last 24 months and no relapses within 12 months. Patients with or without MRI disease activity (patients with gadolinium enhancement lesions [T1Gd +] or new / increasing T2 lesions) will be enrolled in the study. The primary efficacy endpoint for subcutaneous administration of cladribine in SPMS patients will be slowing of brain volume loss relative to placebo.
详细描述
This is a randomized, placebo-controlled, double-blind, multi-center, phase 2 study of subcutaneous cladribine in non-relapsing, secondary progressive multiple sclerosis. Eligible patients will be randomly allocated in a 1:1 ratio to receive either placebo or subcutaneous cladribine at a dose of 1.8 mg/kg of body weight. The study will consist of three periods: screening, treatment, and follow-up. During the screening, the investigators will assess patient eligibility. During the treatment, cladribine will be given over 6 visit every 5-6 weeks. During the follow-up of 96 weeks, safety and efficacy assessments will be carried out on five visits: the first visit will take place 4 weeks after the last cladribine dose, and the remaining visits will take place every 24 weeks.
There will a rescue option of unblinding and treatment with a full dose of cladribine (cladribine arm) or approved medications (placebo arm) for patients with a severe relapse or ≥ 2 non-severe relapses after enrolment or with a substantial neuroimaging disease activity ≥ 4 Gd+ lesions in any scan, ≥ 3 Gd+ lesions in any two scans, ≥ 2 Gd+ lesions in any three scans, or ≥ 9 new/enlarging T2 lesions on any scan compared with baseline).
All raters will be blinded to treatment allocation. All neuroimaging examinations will be evaluated at a central neuroimaging unit by investigators blinded to treatment allocation.
Study type: interventional (clinical trial) Planned enrolment: 188 patients Allocation: randomized Masking: Double (Participant, Investigator) Primary purpose: Treatment Start Date: October 2022
Study design: The study aims to assess the safety and efficacy of subcutaneous cladribine in patients with SPMS who have not experienced relapses over a year and with or without active lesions on neuroimaging. The study will be randomized, placebo-controlled, and double blind. Because no treatment is approved for inactive SPMS, placebo was chosen as the comparator. Patients receiving other treatments for SPMS or immunosuppressant will not be included.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Supplementary medication and additional follow-up visit (U1-U2visit)
- 盲法
- Double (Subject, Monitor, Carer, Analyst, Investigator)
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Written informed consent to participate in the study
- •Diagnosis of SPMS based on the 2017 McDonald criteria, with a relapsing-remitting course at the onset of the disease
- •History of progressive neurological deterioration within at least 24 months: Increase in EDSS score by at least 1 point if EDSS ≤ 5 and by at least 0.5 point if EDSS>
- •A summary written by the researcher explaining why he thinks the patient has progressive disease for at least 24 months.
- •No clinical relapses in the last 12 months
- •Baseline EDSS ≥ 3.5 and ≤ 7.5
- •Age 30-65 years
- •Time from first symptoms at least 10 years
- •For women of childbearing potential: a written declaration of discontinuation of heterosexual intercourse or use of contraception in the study and for at least 6 months after the last dose as defined below: a. The woman must stop heterosexual intercourse or use a contraceptive method with a failure rate <1% per year during treatment. Women are also not allowed to donate eggs during this period. b. A woman of childbearing potential is a woman who has had her first menstrual period, is premenopausal (uninterrupted period of at least 12 months without menstruation) and is not permanently sterile due to surgery (removal of the ovaries, fallopian tubes and / or uterus) or any other reason. found by the researcher. c. Examples of contraception with a failure rate <1% per year are bilateral tubal ligation, partner sterilization, hormonal contraception to suppress ovulation, hormone-secreting IUDs or copper IUDs. d. Hormonal contraception must be used in conjunction with a barrier method. e. Temporary abstinence, such as using a calendar method, is not an acceptable form of contraception.
- •For men: a written declaration to stop heterosexual intercourse in the study and for at least 6 months after the last dose, or to use condoms and contraception in female partners during this period as described above. In addition, statements on not donating semen during the study and for 6 months after the last dose of the drug.
- •Possibility of meeting the requirements of the test protocol in the opinion of the researcher.
排除标准
- •Lack of consent to participate in the study
- •History of cladribine treatment regardless of indication
- •Hypersensitivity to any component of the investigational drug
- •The need to use other immunomodulating or immunosuppressive drugs, including drugs used in secondary progressive MS, e.g. interferon beta-1b, mitoxantrone, siponimod
- •Contraindications for performing magnetic resonance imaging
- •Pregnancy and the period of breastfeeding
- •Lack of consent to the use of effective methods of contraception as defined in the inclusion criteria
- •Diseases of the nervous system (brain or spinal cord tumors, stroke or spinal cord, brain or spinal cord injury, encephalomyelitis, vitamin B12 deficiency, other than multiple sclerosis demyelinating diseases of the central nervous system)
- •Serious accompanying diseases (e.g. cancer, liver and / or kidney failure, heart failure II and III according to NYHA) or other diseases which, in the opinion of the investigator, could threaten the patient's safety in the study or prevent compliance with the requirements of the study protocol
- •Disease relapse <12 months after screening visit
- •Chronic treatment with steroids or immunosuppressants (e.g. azathioprine, methotrexate, cyclosporine) <6 months prior to study entry
- •Disease-modifying therapies: a. Interferons, glatiramer acetate, and dimethyl fumarate must be withdrawn prior to inclusion in the study; they do not require a transition period; b. teriflunomide, fingolimod, natalizumab must be discontinued at least 6 weeks prior to study enrollment; for teriflunomide, the SmPC dropout procedure must be followed if the patient requires enrollment in the study between 2-4 weeks after withdrawal;c. ocrelizumab, mitoxantrone, and alemtuzumab must be discontinued for at least 12 months prior to study enrollment.
- •Relapsing-remitting MS
- •Primary progressive form of MS
- •HBV or HCV infection (positive HBV, positive anti-HBc antibodies or positive anti-HCV antibodies)
- •HIV infection or HIV screening positive (anti-HIV 1/2 antibodies, p24 antigen)
- •Active or latent tuberculosis: a positive QuantiFERON TB Gold (QFT) test during screening or in the 3 months prior to screening (inconclusive test should be repeated; two inconclusive tests are considered positive)
- •Other infections that may worsen with cladribine therapy.
- •Lymphopenia during screening (<1,000 / μl), neutrocytopenia (<1,500 / μl) or thrombocytopenia (<150,000 / μl)
- •Clinical significant abnormalities in the ECG examination according to the researcher's opinion
- •Alcohol or drug abuse in the last 12 months
- •Positive serum pregnancy test during screening
- •History of bone marrow or other organ transplantation
- •Treatment with immunoglobulins or plasmapheresis within the 3 months prior to randomization
- •Treatment with another Investigational medicinal product or medical device in the 6 months prior to randomization
- •At least one abnormal test: a.Creatinine> 1.5 x ULN (ULN; may be repeated if 1.5-2.0 x ULN) b. ALT or AST> 2 x ULN (may be repeated if 1.5-3 x ULN) c. Total Bilirubin> 1.5 x ULN (may be repeated if 1-3 x ULN) d. Hemoglobin <9.5 g / dL (can be repeated if 9-9.4 g / dL)
- •Patient is not fully vaccinated against COVID-19, i.e. at least 6 weeks have not elapsed since the last dose of vaccination.
- •Vaccination with any vaccine within less than 6 weeks
- •The patient has not been screened for neoplasms or the tests performed suggest neoplasm or further tests for neoplasm (chest X-ray PA + side for women and men, mammography or ultrasound of breasts for women, cytology for women, PSA for men).
- •Lack of measurable serum levels of anti-varicella / herpes zoster antibodies.
- •Anticoagulant therapy (oral or parenteral) or anti-platelet therapy other than acetylsalicylic acid.
研究组 & 干预措施
Experimental
Drug: Cladribine at a dose of 1.8 mg/kg of body weight. Cladribine will be given subcutaneously over 6 visits every 5-6 weeks.
干预措施: Cladribine Subcutaneous Injection (Drug)
Control
Comparator: Placebo matched to the subcutaneous injection of cladribine.
干预措施: 0.9% Chloride Injection Sodium (Drug)
结局指标
主要结局
Percent brain volume change from last cladribine dose (week 26) to end of study (week 122).
Percent brain volume change from last cladribine dose (week 26) to end of study (week 122).
次要结局
- 1.Time to 24-week confirmed composite progression of disability defined as the occurrence of any of the following events: an increase in EDSS score, in time of Timed 25-Foot Walk and 9-Hole Peg Test. 2.Change from baseline in cognitive function (CANTAB, CVLT, SDMT) and quality of life (MSQeL-54) 3.Neuroimaging: number of Gd+ lesions, new T2 lesions, QSM rim+ lesions, volume of T1 lesions (black holes), volume of cervical spinal cord in T1; 4. Serum level of NfL, GFAP, oligoclonal bands presence
研究者
II Klinika Neurologii
Scientific
Instytut Psychiatrii I Neurologii