A Multicenter, Rollover Study to Evaluate the Long-Term Safety and Efficacy of Atacicept
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 476
- 试验地点
- 5
- 主要终点
- Objective: To evaluate the long-term safety and tolerability of atacicept in participants who have completed the protocol-defined treatment period in a parent study
研究概览
简要总结
Phase 2, multicenter, rollover study to evaluate long-term safety and tolerability for atacicept in participants with IgAN who completed the protocol-defined treatment period of a Vera-sponsored study (parent study). Eligible participants will receive atacicept 150 mg once weekly (QW) self-administered subcutaneously (SC). Participants will be grouped by whether they are restarting atacicept after cessation in the parent study (Group 1: Atacicept Drug Holiday) or are continuing atacicept with no disruption in treatment (Group 2: Continuous Atacicept Treatment). First dose is defined as Day 1 and should not occur prior to the completed protocol-defined treatment periods in the parent study.
Atacicept is capable of binding to all known conformations of BLyS and APRIL and is thus expected to inhibit the maturation, differentiation, and effector function of B cells. These mechanisms are consistent with the known pharmacological effects of atacicept, which include depletion of peripheral B cell subsets, naïve follicular, marginal zone and long lived plasma cell B cell subsets, impeded germinal center reaction, and reduced immunoglobulins, while leaving immature B cells and memory B cells intact (Dillon 2006, Dillon 2010, Gross 2001, Moore 1999, Schneider 1999, Schneider 2005). These effects are predicted to reduce the production and subsequent deposition of Gd-IgA1-containing immune complexes in kidney glomeruli, and thus reduce the extent of kidney injury in IgAN patients.
This study is intended to provide patients with extended and continuous access to atacicept before commercial availability in their country/region. Participants will be treated in this study for up to 3 years but could end treatment in this study once atacicept is commercially available in their country/region or if the Sponsor terminates the clinical development program. Participants who discontinue study drug early (prior to the reasons provided above) will complete an Early Termination (ET) visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Group 1 :Atacicept Drug Holiday
- •Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study assessments
- •Completed the protocol-defined treatment period on treatment in a parent study of atacicept in patients with IgAN
- •Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg at screening and Day 1
- •A participant who was assigned female at birth is eligible if not pregnant (ie, after a confirmed menstrual period, a negative serum pregnancy test at screening and has a negative urine pregnancy test at Day 1), is not breastfeeding (for at least three months prior to screening), and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP).
- •OR Is a WOCBP who agrees to use a highly effective contraceptive method (ie, has a failure rate of less than 1% per year), at least 7 days prior to enrollment, through 175 days after the last dose of study drug.
排除标准
- •Evidence of rapidly progressive glomerulonephritis-loss of greater than or equal to 50% of eGFR within 3 months of screening.
- •Evidence of nephrotic syndrome-serum albumin less than 30g/L in association with UPCR greater than 3.5 mg/mg within 6 months of screening.
- •Currently on chronic dialysis or expected to initiate dialysis within 12 weeks of screening.
- •Renal or other organ transplantation prior to, or expected during, the study, with the exception of corneal transplants.
- •For Atacicept Drug Holiday Group only Prohibited medications: -Use of systemic corticosteroids (including oral budesonide) or immunosuppressive medications eg, MMF, azathioprine, cyclophosphamide, hydroxychloroquine for the treatment of IgAN within 2 months prior to Screening. For glucocorticosteroids, Systemic is defined as oral, rectal or injectable intravenous or intramuscular routes of administration. Other routes of administration are allowed, including intra-articular, inhaled, topical, ophthalmic, optic and intranasal.
- •Use of B-cell–directed biologic therapies including belimumab, rituximab, ocrelizumab within 12 months of screening.
- •Use of other biologics eg, anti-TNF, abatacept, anti-IL-6 and investigational biologics for the treatment of IgAN within 6 months of screening.
- •Clinically significant or predefined abnormalities per central laboratory tests at screening, meeting any of the criteria below.
- •Clinical evidence of immunosuppression and or hypogammaglobulinemia as determined by the Investigator.
- •For Atacicept Drug Holiday Group only: Aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase level greater than 2.5 × upper limit of normal ULN or total bilirubin greater than 1.5 x ULN. If the participant has a known history of Gilberts -history of isolated increase in total bilirubin without increase in liver transaminases, contact the Medical Monitor for further discussion.
- •For Atacicept Drug Holiday Group only: Administration of live and live-attenuated vaccinations within 30 days prior to enrollment.
- •For Atacicept Drug Holiday Group only: History or current diagnosis of any demyelinating disease such as, but not restricted to, multiple sclerosis or optic neuritis.
- •Active clinically significant viral, bacterial or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks prior to enrollment, or completion of oral anti-infectives within 2 weeks prior to enrollment, ora history of recurrent infections ie, 3 or more of the same type of infection in a 12-month rolling period. Vaginal candidiasis, onychomycosis and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled are not exclusionary.
- •For Atacicept Drug Holiday Group only: If the participant is undergoing current treatment for latent tuberculosis infection, they must have received at least 4 continuous weeks of an appropriate LTBI treatment prior to screening without evidence of re-exposure to be eligible for this study. If on LTBI treatment at the Screening visit, the participant will be expected to complete an appropriate LTBI treatment regimen to remain in the trial.
- •For Atacicept Drug Holiday Group only: History of acute or chronic infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus.
- •Participants who are positive hepatitis B surface antigen HBsAg are excluded.
- •Participants who are HBsAg negative, hepatitis B core antibody HBcAb positive, hepatitis B surface antibody HBsAb positive with no detectable hepatitis B virus HBV DNA are eligible but will require monthly HBV DNA monitoring through safety follow-up.
- •Participants with positive hepatitis C HCV RNA are excluded, however participants who are HCV antibody positive with no detectable HCV RNA at least 24 weeks after completion of antiviral therapy are eligible.
- •For Atacicept Drug Holiday Group only: History of splenectomy.
- •For Atacicept Drug Holiday Group only: History of malignancy hematologic or solid tumor within 5 years prior to Day 1, except adequately treated basal cell or squamous cell carcinomas of the skin no more than 3 lesions requiring treatment in lifetime or carcinoma in situ or cervical intraepithelial neoplasia of the uterine cervix.
- •Known hypersensitivity to atacicept or any component of the formulated atacicept.
- •For Atacicept Drug Holiday Group only: Major surgery within 6 weeks prior to screening or planned/expected major surgery during the study period including the safety follow-up period.
- •Major surgery often involves opening one of the major body cavities abdomen or chest and or use of general anesthesia. Types of surgery that have the highest risk include heart or lung, liver, abdomen, or major operations on the bones and joints eg, hip replacement.
- •Clinically significant history of alcohol or drug abuse in the 1 year prior to Day 1 as per Investigator opinion.
- •Unwillingness or lack of capacity to follow all study procedures.
- •For Atacicept Drug Holiday Group only: Treatment with other investigational agents within the last 4 weeks or 5 half-lives, whichever is longer, prior to screening.
结局指标
主要结局
Objective: To evaluate the long-term safety and tolerability of atacicept in participants who have completed the protocol-defined treatment period in a parent study
时间窗: Baseline until end of study up to week156
Endpoint: Long-term safety and tolerability of atacicept as assessed by routine clinical and laboratory tests and adverse events
时间窗: Baseline until end of study up to week156
次要结局
- Objective:(To evaluate the effect of atacicept on change in proteinuria)
研究者
Dr Suceena Alexander
Institute