NCT07842523尚未招募2 期
Safety and Efficacy of Obinutuzumab in Systemic Sclerosis: a Phase II, Randomized, Double-blinded Versus Placebo-controlled Trial"
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- the percentage of patients achieving a 20% CRISS improvement from baseline in at least 3 of the 5-core set second step leasures if the Revised CRISS at 360 days.
研究概览
简要总结
The purpose of this study is to determine if obinutuzumab is effective in systemic sclerosis
详细描述
Systemic sclerosis (SSc) is a rare systemic autoimmune connective tissue-disease characterized by fibrosis, inflammation, and vasculopathy. SSc is responsible for skin fibrosis that can either be limited or diffuse. The latter phenotype of the disease is commonly associated with visceral involvement and therefore similar to graft versus host disease (GvHD) reaction. It can be life threatening in case of pulmonary or cardiovascular involvement. Nonetheless SSc remains a severe disease responsible for important disability and a poor quality of life.
B cell depletion and anti CD20 antibody (rituximab) have proven safety and efficacy in treating diffuse SSc. Obinutuzumab is a new generation anti-CD20 antibody for which efficacy and safety should be evaluated in SSc.
The OBINUSS trial was thus designed to evaluate obinutuzumab safety and efficacy in SSc.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Adult patient (>/= 18 years old),
- •Patient with a diagnosis of SSc, as defined by the American College of Rheumatology / EULAR 2013 criteria,
- •Patient with a diffuse SSc, as defined according to Leroy et al.
- •Patient with a SSc disease duration of less than 8 years (defined as time from first non-Raynaud phenomenon manifestation) or with an active SSc disease, as defined by EUSTAR disease activity score,
- •Patient with a modified Rodnan skin score (mRSS) > /= 10 and < /= 35 units at screening,
- •Negative pregnancy test for woman of childbearing potential, woman of childbearing potential should have reliable contraception during the treatment period and up to 18 months after stopping it Women are considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient
- •Patient able to give written informed consent prior to participation in the study,
- •Affiliation to a social security scheme (profit or being entitled).
- •If patients receive mycophenolate or methotrexate for SSc, these need to be on stable dose as follows:
- •Mycophenolate mofetil/sodium: stable dose for at least 2 months prior to randomisation Methotrexate: stable dose and route of administration for at least 2 months prior to randomisation
- •- Anti-fibrotic drugs such as nintedanib is permitted
排除标准
- •Any B-cell depleting (e.g., anti-CD20, anti-CD19) or anti-plasma cell therapy such as, but not limited to, obinutuzumab, rituximab, ocrelizumab, ofatumumab, or bortezomib less than 9 months prior to screening or during screening. If anti-CD20 or anti-CD19 therapy has been received between 9 and 12 months prior to screening, the peripheral CD19+ B-cell count must be over 25 cells/μL
- •Cyclophosphamide, tacrolimus, ciclosporin, or voclosporin during the 2 months prior to screening or during screening
- •Any biologic therapy (other than anti-CD20, anti-CD19, or anti-plasma cell) such as, but not limited to, belimumab, ustekinumab, anifrolumab, secukinumab, or atacicept during the 2 months prior to screening or during screening
- •Inhibitors of Janus-associated kinase (JAK), Bruton's tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2), including baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or fenebrutinib or any investigational agent during the 2 months prior to screening or during screening
- •Any live vaccine during the 28 days prior to screening or during screening
- •High risk for clinically significant bleeding or any condition requiring plasmapheresis, IV immunoglobulin, or acute blood product transfusions during the 28 days prior the screening
- •Active infection with SARS-CoV-2 or patients not fully vaccinated following national recommendations against SARS-CoV-2
- •Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude patient participation
- •HIV infection: for participants with unknown HIV status, HIV testing will be performed locally at screening if required by local regulations.
- •Active infection of any kind, excluding fungal infection of the nail beds. Any major episode of infection that also fulfills any of the following criteria:
- •Requires hospitalization during the 8 weeks prior to screening or during screening
- •Requires treatment with IV antibiotics (or anti-infectives) during the 8 weeks prior to screening or during screening
- •Requires treatment with oral antibiotics (or anti-infectives) during the 2 weeks prior to screening or during screening
- •Antibiotics or anti-infectives given in the absence of a major episode of infection are not exclusionary.
- •History of serious recurrent or chronic infection
- •History of progressive multifocal leukoencephalopathy (PML)
- •History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ, within the past 5 years (Participants with non-melanomatous carcinomas of the skin that have been treated or excised and have resolved are eligible).
- •Major surgery requiring hospitalization during the 4 weeks prior to or during screening
- •Current alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening or during screening
- •Intolerance or contraindication to study therapies, including any of the following:
- •*History of severe allergic or anaphylactic reactions to monoclonal antibodies or known hypersensitivity to any component of the obinutuzumab infusion
- •Any of the following laboratory parameters:
- •AST or ALT above 2.5 upper limit normal range
- •Neutrophils <1.5x103/mL
- •Positive hepatitis B surface antigen (HBsAg) Participants who are HBsAg negative and hepatitis B core antibody (HBcAb) positive with no detectable hepatitis B virus (HBV) DNA are eligible but will require monthly HBV DNA monitoring until 12 months after the last dose of obinutuzumab or placebo.
- •Positive hepatitis C serology Participants with positive hepatitis C antibody test result with no detectable hepatitis C virus (HCV) RNA for at least 6 months after completion of antiviral therapy are eligible but will require monthly HCV RNA monitoring until 12 months after the last dose of obinutuzumab or placebo.
- •Hemoglobin below 7 g/dL
- •Platelet count below 50,000/L
- •Pregnant or breastfeeding woman, or woman who refuses to use an effective contraception during the study course;
- •Protected adults (including individual under legal guardianship by court order or curatorship) or adults deprived of liberty;
- •Patient participating in another investigational therapeutic study in the 3 months preceding inclusion;
- •Patients treated with CAR-T cell immunotherapy
研究组 & 干预措施
Placebo
Placebo Comparator
1000mg of i.v placebo at D1, D15 and D180
干预措施: Placebo (Drug)
Obinutuzumab
Experimental
1000mg of i.v obinutuzumab at D1, D15 and D180
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
the percentage of patients achieving a 20% CRISS improvement from baseline in at least 3 of the 5-core set second step leasures if the Revised CRISS at 360 days.
时间窗: 360 days
次要结局
- Mortality up to 360 days(360 days)
- Occurrence of Adverse Events up to 360 days(At 90, 180, 270 and 360 days)
- Occurrence of Severe Adverse Events up to 360 days(At 90, 180, 270 and 360 days)
- Occurrence of AE of specific interest previously mentioned(At 90, 180, 270 and 360 days)
- Proportion of patients who achieved CRISS20 of the revised CRISS(At days 180 and 270)
- Proportions of patients who achieved 30%, 40%, 50% ,60%, 70%, 80%, 90% and 100% improvement from baseline in at least 3 of the 5 core set measures of the revised CRISS(At days 180, 270 and 360)
- Change in the Combined Response Index in Diffuse Systemic Sclerosis (CRISS) score.These scales range from 0 (minimum) to 1(maximum) points. Higher score mean better outcome(At days 180, 270 and 360)
- Change in Physicians visual analogue scales over 18 months(At 18 months)
- Change in patients visual analogue scales over 18 month(At 18 months)
- Change in modified Rodnan skin score(At 90, 180, 270 and 360 days)
- Proportion of patients with an improved modified Rodnan skin score.(At 90, 180, 270, 360 days)
- Absolute change from baseline in Forced Vital Capacity FVC(At days 180, 270, and days 360)
- Absolute change from baseline in DLCO(At day 180, 270 and day 360)
- Proportion of patients with an active disease according to the EUSTAR SSc activity score.(At 90, 180, 270 and 360 days.)
- Time to treatment failure.(Over the 48 weeks)
- Change in skin transcriptome.(At 360 days)
- Analysis of the mouth opening trajectory(At days 0, 90, 180, 270 and 360)
- SF-36 scale(At day 0, 90, 180, 270 and day 360)
- EQ5D5L scale(At day 0, 90, 180, 270 and day 360)
- HAQ-DI scale(At day 0, 90, 180, 270 and day 360.)
- SHAQ scale(At day 0, 90, 180, 270 and day 360.)
- Saint Georges Respiratory Hospital Questionnaire (SGRH)(At day 0, 90, 180, 270 and day 360)
- King Brief's Interstitial Lung Disease questionnaire (KBILD)(At day 0, 90, 180, 270 and day 360)
- Scleroderma skin patients reported outcome (SSPRO)(At day 0, 90, 180, 270 and day 360)
- PRO self-administered questionnaire (ScleroID)(At day 0, 90, 180, 270 and day 360)
研究者
研究点 (1)
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