An Open-Label Phase 1/2 Study Evaluating the Safety and Efficacy of Etentamig (ABBV-383) in AL Amyloidosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 76
- 试验地点
- 44
- 主要终点
- Dose Escalation Only: Number of Participants with Dose-Limiting Toxicities (DLT)
研究概览
简要总结
Immunoglobulin light chain (AL) amyloidosis is the most common form of systemic amyloidosis. AL amyloidosis has many root causes and is characterized by the overproduction of AL that are secreted by clonal bone marrow plasma cells. This is a study to determine adverse events and change in disease activity in adult participants with AL amyloidosis treated with ABBV-383.
Etentamig (ABBV-383) is an investigational drug being developed for the treatment of AL amyloidosis. This study in broken into 2 parts (dose escalation and dose expansion) with 4 arms. During dose escalation (arms 1-3) participants will receive 1 of 3 doses of ABBV-383 to determine the part 2 dose. After completion of the dose escalation portion of the study, the dose expansion (part 2) portion of the study will begin. One arm (arm 4) will begin and participants will receive a dose determined during the dose escalation portion (part 1). Around 76 adult participants with relapsed/refractory AL amyloidosis will be enrolled at approximately 25 sites across the world.
Participants will receive Etentamig (ABBV-383) as an infusion into the vein for up to approximately 2 year study duration.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Diagnosis of primary systemic immunoglobulin light chain (AL) amyloidosis.
- •Eastern Cooperative Oncology Group (ECOG) performance status of <=
- •Have at least 1 organ historically impacted by AL amyloidosis.
- •Considered AL amyloidosis cardiac risk stage 1, 2, or 3a, or considered risk stage 3b with stable cardiac function and markers for 3 months prior to dosing, and have measurable disease of AL amyloidosis as defined by difference between involved and uninvolved free light chains (dFLC) >= 50 mg/L or meeting high-risk dFLC progression criteria after immediate prior line of therapy.
- •Has previously been exposed to a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody.
排除标准
- •Known history of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.
- •Known allergic reaction, significant sensitivity, or intolerance to constituents of the study treatment (and excipients) and/or other products in the same class.
- •Participant has the following conditions:
- •Other non-AL amyloid disease;
- •Previous or current diagnosis of symptomatic multiple myeloma (MM), including the presence of lytic bone disease, plasmacytomas, >= 60% plasma cells in the bone marrow, or hypercalcemia (defined as corrected calcium > 11 mg/dL);
- •Active plasma cell leukemia (i.e., either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential);
- •Waldenström's macroglobulinemia;
- •Acute diffuse infiltrative pneumopathy;
- •Major surgery within 28 days prior first dose or planned during study participation;
- •History of organ transplant requiring continued use of immunosuppressants;
- •Acute infections within 14 days prior first dose requiring parenteral therapy (antibiotic, antifungal, or antiviral);
- •Participant has received an autologous stem cell transplant (SCT) within 12 weeks or an allogeneic SCT within 1 year of the first dose of study treatments.
研究组 & 干预措施
Dose Escalation: ABBV-383 (etentamig) Dose A
Participants will receive ABBV-383 (etentamig) dose A during the approximately 2 year study duration.
干预措施: ABBV-383 (Etentamig) (Drug)
Dose Escalation: ABBV-383 (etentamig) Dose B
Participants will receive ABBV-383 (etentamig) dose B during the approximately 2 year study duration.
干预措施: ABBV-383 (Etentamig) (Drug)
Dose Escalation: ABBV-383 (etentamig) Dose C
Participants will receive ABBV-383 (etentamig) dose C during the approximately 2 year study duration.
干预措施: ABBV-383 (Etentamig) (Drug)
Dose Expansion: ABBV-383 (etentamig)
Participants will receive ABBV-383 (etentamig) expansion dose B during the approximately 2 year study duration.
干预措施: ABBV-383 (Etentamig) (Drug)
结局指标
主要结局
Dose Escalation Only: Number of Participants with Dose-Limiting Toxicities (DLT)
时间窗: Up to 28 Days
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Dose Expansion Only: Percentage of Participants who Achieve Hematologic Complete Response (CR)
时间窗: Up to 4 years
Hematologic CR is defined as the percentage of participants who achieve normalization of free light chain levels, negative serum immunofixation, negative urine immunofixation as determined per the modified International Amyloidosis Consensus Criteria (IACC).
Dose Expansion Only: Number of Participants with DLTs
时间窗: Up to 4 years
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Number of Participants with Adverse Events (AEs)
时间窗: Up to 4 years
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
次要结局
- Hematologic Overall Response Rate (ORR)(Up to 4 Years)
- Time to Hematologic CR(Up to 4 Years)
- Duration of Hematologic CR(Up to 4 Years)
- Organ Response Rate (OrRR)(Up to 4 Years)
- Time to Organ Response(Up to 4 Years)
- Dose Escalation Only: Percentage of Participants who Achieve Hematologic CR Rate as Determined(Up to 4 years)