A Phase 2 Study to Investigate the Safety and Efficacy of Elsubrutinib and Upadacitinib Given Alone or in Combination (ABBV-599 Combination) in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 341
- 试验地点
- 160
- 主要终点
- Percentage of Participants Achieving SLE Responder Index (SRI)-4 and Steroid Dose ≤ 10 mg Prednisone Equivalent Once a Day (QD) at Week 24
研究概览
简要总结
The main objective of this study was to evaluate the safety and efficacy of elsubrutinib, upadacitinib (UPA), and ABBV-599 (elsubrutinib/upadacitinib) High Dose and Low Dose combinations vs placebo for the treatment of signs and symptoms of Systemic Lupus Erythematosus (SLE) in participants with moderately to severely active SLE and to define doses for further development.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has clinical diagnosis of Systemic Lupus Erythematosus (SLE) at least 24 weeks prior to Screening, meeting at least 4 of the 11 revised Criteria for Classification of SLE according to the 1997 Update of the 1982 American College of Rheumatology (ACR) OR meeting at least 4 of the 2012 SLICC classification criteria, including at least 1 clinical criterion and 1 immunologic criterion.
- •At Screening, must have at least one of the following:
- •antinuclear antibody (ANA)+ (titer ≥ 1:80)
- •anti-dsDNA+
- •anti-Smith+
- •SLEDAI-2K (SLE Disease Activity Index) ≥ 6 despite background therapy as reported and independently adjudicated (clinical score ≥ 4, excluding lupus headache and/or organic brain syndrome) at Screening:
- •If 4 points of the required entry points are for arthritis, there must also be a minimum of 3 tender and 3 swollen joints.
- •If participant has rash and Principal Investigator (PI) considers it to be attributable to SLE, participant must consent to skin photograph collection for adjudication.
- •Score must be re-confirmed at the Baseline visit.
- •Physician's Global Assessment (PhGA) ≥ 1 during screening period.
- •Must be on background treatment, stable for 30 days prior to Baseline and throughout the study with antimalarial(s), prednisone (or prednisone equivalent) (≤ 20 mg), azathioprine (≤ 150 mg), mycophenolate (<2 g), leflunomide (≤ 20 mg), cyclosporine, tacrolimus, and/or methotrexate (MTX) (≤ 20 mg).
- •No combinations of the above with immunomodulators other than prednisone (or equivalents) and antimalarials.
排除标准
- •Participant using intravenous (IV) or intramuscular (IM) corticosteroids greater than or equal to a 40 mg prednisone-equivalent bolus within 30 days of planned randomization.
研究组 & 干预措施
Elsubrutinib placebo/upadacitinib placebo
Placebo capsule for elsubrutinib once a day by mouth for up to 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for up to 48 weeks
干预措施: Placebo for elsubrutinib (Drug)
Elsubrutinib placebo/upadacitinib placebo
Placebo capsule for elsubrutinib once a day by mouth for up to 48 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for up to 48 weeks
干预措施: Placebo for upadacitinib (Drug)
ABBV-599 High Dose (Elsubrutinib 60 mg/upadacitinib 30 mg)
60 mg elsubrutinib capsule once a day by mouth for up to 48 weeks; 30 mg upadacitinib film-coated tablet once a day by mouth for up to 48 weeks
干预措施: Elsubrutinib (Drug)
ABBV-599 High Dose (Elsubrutinib 60 mg/upadacitinib 30 mg)
60 mg elsubrutinib capsule once a day by mouth for up to 48 weeks; 30 mg upadacitinib film-coated tablet once a day by mouth for up to 48 weeks
干预措施: Upadacitinib (Drug)
Elsubrutinib placebo/upadacitinib 30 mg
Placebo capsule for elsubrutinib once a day by mouth for up to 48 weeks; 30 mg upadacitinib film-coated tablet once a day by mouth for up to 48 weeks
干预措施: Placebo for elsubrutinib (Drug)
Elsubrutinib placebo/upadacitinib 30 mg
Placebo capsule for elsubrutinib once a day by mouth for up to 48 weeks; 30 mg upadacitinib film-coated tablet once a day by mouth for up to 48 weeks
干预措施: Upadacitinib (Drug)
ABBV-599 Low Dose (Elsubrutinib 60 mg/upadacitinib 15 mg)
60 mg elsubrutinib capsule once a day by mouth for up to 24 weeks; 15 mg upadacitinib film-coated tablet once a day by mouth for up to 24 weeks
干预措施: Elsubrutinib (Drug)
ABBV-599 Low Dose (Elsubrutinib 60 mg/upadacitinib 15 mg)
60 mg elsubrutinib capsule once a day by mouth for up to 24 weeks; 15 mg upadacitinib film-coated tablet once a day by mouth for up to 24 weeks
干预措施: Upadacitinib (Drug)
Elsubrutinib 60 mg/upadacitinib placebo
60 mg elsubrutinib capsule once a day by mouth for up to 24 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for up to 24 weeks
干预措施: Elsubrutinib (Drug)
Elsubrutinib 60 mg/upadacitinib placebo
60 mg elsubrutinib capsule once a day by mouth for up to 24 weeks; placebo film-coated tablet for upadacitinib once a day by mouth for up to 24 weeks
干预措施: Placebo for upadacitinib (Drug)
结局指标
主要结局
Percentage of Participants Achieving SLE Responder Index (SRI)-4 and Steroid Dose ≤ 10 mg Prednisone Equivalent Once a Day (QD) at Week 24
时间窗: Baseline, Week 24
SLE Responder Index (SRI)-4 is defined as follows with all criteria compared to Baseline: * ≥ 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score * No worsening of the overall condition (\< 0.3 point increase in Physician's Global Assessment \[PhGA\]) * No new British Isles Lupus Assessment Group (BILAG) A or more than 1 new BILAG B disease activity scores (i.e., no organ system changes from baseline B/C/D/E to A and no more than 1 organ system changes from baseline C/D/E to B). A letter score is assigned to each organ system with following indications: A = severe, B = moderate, C = mild, D = inactive with prior history, and E = inactive with no history.
次要结局
- Percentage of Participants Achieving British Isles Lupus Assessment Group (BILAG) Based Combined Lupus Assessment (BICLA) Response at Week 24(Baseline, Week 24)
- Percentage of Participants Achieving SLE Responder Index (SRI)-4 at Week 24(Baseline, Week 24)
- Percentage of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 24(Baseline, Week 24)
- Change From Baseline in Daily Prednisone Dose at Week 24(From Baseline to Week 24)
- Number of Flares Per Patient-year by Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI Flare Index Through Week 24(From Baseline to Week 24)