A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Obinutuzumab in Adolescent Patients With Active Class III or IV Lupus Nephritis, Including an Evaluation of Open Label Safety and PK in a Cohort of Pediatric Patients (Aged 5 to < 12)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 54
- 主要终点
- Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP)
研究概览
简要总结
This phase II, randomized, double-blind, placebo-controlled study is designed to evaluate the safety, efficacy and pharmacokinetics (PK) of obinutuzumab in adolescent participants (AP) aged 12 to less than 18 with biopsy-confirmed proliferative lupus nephritis (LN). It will also evaluate open label safety and PK of obinutuzumab in pediatric participants (PP), aged 5 to <12 with LN.
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)
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who are age 12 to <18 years at the time of randomization
- •Participants who are age 5 to <12 years (younger participant cohort) at the time of randomization once recruitment is open. (Investigators will be notified by the Sponsor when recruitment is open to this younger population)
- •International Society of Nephrology and the Renal Pathology Society (ISN/RPS) 2003 Class III or IV active LN demonstrated on renal biopsy performed in the 12 months prior to or during screening
- •Class V disease may be present in addition to Class III or IV LN, but participants with isolated Class V disease are not eligible
- •Diagnosis of SLE according to the Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria
- •Significant proteinuria defined by a UPCR above > 0.5 based on a first-morning void (FMV) collection at screening
- •During the 12 months prior to or during screening, all participants must have received at least one dose of pulse-range IV methylprednisolone (typically 30 mg/kg, maximum of 1000 mg per dose) or equivalent for the treatment of the current episode of active LN.
排除标准
- •Severe, active central nervous system (CNS) SLE, including retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke, cerebellar ataxia, or dementia
- •Sclerosis in >50% of glomeruli on renal biopsy
- •Purely chronic Class III(c) or Class IV(c) disease on renal biopsy, defined as the absence of any active lesions
- •Presence of rapidly progressive glomerulonephritis
- •Pure Class V LN
- •Intolerance or contraindication to study therapies
- •Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV anti-infective medications within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization
- •History of or currently active primary or secondary immunodeficiency, including known history of HIV infection and other severe Immunodeficiency blood disorders
- •History of serious recurrent or chronic infection
- •History of or current cancer, including solid tumors, hematological malignancies, and carcinoma in situ (except basal cell carcinoma and squamous cell carcinoma of the skin that have been excised and cured) within the past 5 years
- •Significant or uncontrolled concomitant medical disease which, in the investigator's opinion, would preclude participant participation
- •Currently active alcohol or drug abuse or history of alcohol or drug abuse
研究组 & 干预措施
Blinded Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).
干预措施: Acetaminophen/paracetamol (Drug)
Blinded Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).
干预措施: Diphenhydramine hydrochloride (HCl) (Drug)
Blinded Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).
干预措施: Mycophenolate Mofetil (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.
干预措施: Acetaminophen/paracetamol (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.
干预措施: Diphenhydramine hydrochloride (HCl) (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.
干预措施: Mycophenolate Mofetil (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.
干预措施: Methylprednisolone (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.
干预措施: Prednisone (Drug)
Open-Label Obinutuzumab
Younger participants aged 5 to <12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.
干预措施: Obinutuzumab (Drug)
Open-Label Obinutuzumab
Younger participants aged 5 to <12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.
干预措施: Acetaminophen/paracetamol (Drug)
Open-Label Obinutuzumab
Younger participants aged 5 to <12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.
干预措施: Diphenhydramine hydrochloride (HCl) (Drug)
Open-Label Obinutuzumab
Younger participants aged 5 to <12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.
干预措施: Mycophenolate Mofetil (Drug)
Open-Label Obinutuzumab
Younger participants aged 5 to <12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.
干预措施: Prednisone (Drug)
Open-Label Obinutuzumab
Younger participants aged 5 to <12 will receive obinutuzumab 1000 mg IV infusions on Days 1, 14, Week 24, Week 26 and Week 52.
干预措施: Methylprednisolone (Drug)
Blinded Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).
干预措施: Obinutuzumab (Drug)
Blinded Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).
干预措施: Methylprednisolone (Drug)
Blinded Obinutuzumab
Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusions on Day 1, Day 14, Week 24, Week 26 and Week 52. Participants with a body weight of 45 kg or more will receive the 1000 mg dose. Participants with a body weight below 45 kg will receive a weight adjusted dose of 20 mg/kilogram (kg).
干预措施: Prednisone (Drug)
Placebo
Placebo participants will receive obinutuzumab matched placebo on Day 1, Day 14, Week 24, Week 26 and Week 52.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants who Achieve a Complete Renal Response (CRR) (AP)
时间窗: Week 76
CRR is defined as achievement of all of the following: * Urinary protein-to-creatinine ratio (UPCR) \<0.5 g/g * Estimated Glomerular Filtration Rate (eGFR) \>=85% of baseline * No occurrence of intercurrent events
Percentage of Participants with Adverse Events (PP)
时间窗: Baseline to Week 76
次要结局
- Percentage of Participants with Anti-drug Antibodies (ADA) (AP)(Weeks 0, 24, 52 and 76)
- Change in Pediatric Quality of Life Inventory-Multidimensional Fatigue Scale (PedsQL)-Fatigue Total Score (AP)(Baseline to Week 76)
- Change in UPCR (AP)(Baseline to Week 76)
- Change in eGFR (AP)(Baseline to Week 76)
- Percentage of Participants who Experience Treatment Failure (AP)(Week 12 to Week 76)
- Change in anti-dsDNA titers (AP)(Baseline to Week 76)
- Change in C4 Complement Levels (AP)(Baseline to Week 76)
- Serum Concentrations of Obinutuzumab (AP)(Baseline to Week 76)
- Percentage of Participants who Achieve a PRR (AP)(Week 76)
- Percentage of Participants Achieving an Overall Response (CRR or PRR) (AP)(Weeks 24, 52, and 76)
- Time to Onset of CRR over the Course of 76 weeks (AP)(Up to Week 76)
- Percentage of Participants Achieving a CRR (AP)(Weeks 24 and 52)
- Percentage of Participants who Achieve CRR with Successful Prednisone Taper (AP)(Week 76)
- Change in C3 Complement Levels (AP)(Baseline to Week 76)
- Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) (AP)(Baseline to Week 76)
- Percentage of Participants Achieving a CRR (PP)(Week 76)
- Percentage of Participants Achieving an Overall Response (PP)(Week 76)
- Percentage of Participants with Adverse Events According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 (AP)(Baseline to Week 76)
- Percentage of Participants Achieving B-cell Depletion (AP)(Baseline, Weeks 4, 24, 52 and 76)
- Change from Baseline in Child Health Questionnaire-Parent Form 28 (CHQ-PF28) Domain Scores (AP)(Baseline to Week 76)
- Percentage of Participants with ADAs (PP)(Weeks 0, 24, 52 and 76)
- Change in anti-dsDNA titers (PP)(Baseline to Week 76)
- Relationship Between ADA Status and Percentage of Participants Achieving a CRR (AP)(Weeks 24, 52 and 76)
- Percentage of Participants who Achieve CRR with Successful Prednisone Taper (PP)(Week 76)
- Change in eGFR (PP)(Baseline to Week 76)
- Percentage of Participants Achieving B-cell Depletion (PP)(Baseline, Weeks 4, 24, 52 and 76)