A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Immunoglobulin Light Chain (AL) Amyloidosis Receiving ABBV-383 as an Intravenous (IV) Infusion

Study Overview
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Brief Summary
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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. ABBV-383 is an investigational drug being developed for the treatment of AL amyloidosis. This study in broken into 2 parts (dose escalation and safety expansion) with 5 arms. During dose escalation (arms 1-3) participants will receive 1 of 3 doses of ABBV-383 to determine the part 2 doses. After completion of the dose escalation portion of the study, the safety expansion (part 2) portion of the study will begin. Two arms (arm 4-5) will begin and participants will receive 1 of 2 doses as determined during the dose escalation portion (part 1). Around 76 adult participants with relapsed/refractory AL amyloidosis will be enrolled at approximately 20 sites across the world. Participants will receive 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.

Official Title
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An Open-Label Phase 1b Study Evaluating the Safety and Efficacy of ABBV-383 in AL Amyloidosis

Conditions
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Immunoglobulin Light Chain (AL) Amyloidosis

Intervention / Treatment
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* Drug: ABBV-383


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary systemic immunoglobulin light chain (AL) amyloidosis. Eastern Cooperative Oncology Group (ECOG) performance status of <= 2. Have at least 1 organ historically impacted by AL amyloidosis. Considered AL amyloidosis risk stage 1, 2, or 3a and have measurable disease of AL amyloidosis as defined by difference between involved and uninvolved free light chains (dFLC) >= 50 mg/L. Has previously been exposed to a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody. Exclusion Criteria: 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 drugs (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 drug treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation: ABBV-383 Dose A<br>Participants will receive ABBV-383 dose A during the approximately 2 year study duration. | Drug: ABBV-383<br>* Intravenous Infusion<br>* Other names: TNB-383B;|
| Experimental: Dose Escalation: ABBV-383 Dose B<br>Participants will receive ABBV-383 dose B during the approximately 2 year study duration. | Drug: ABBV-383<br>* Intravenous Infusion<br>* Other names: TNB-383B;|
| Experimental: Dose Escalation: ABBV-383 Dose C<br>Participants will receive ABBV-383 dose C during the approximately 2 year study duration. | Drug: ABBV-383<br>* Intravenous Infusion<br>* Other names: TNB-383B;|
| Experimental: Safety Expansion: ABBV-383 Expansion A<br>Participants will receive ABBV-383 expansion dose A during the approximately 2 year study duration. | Drug: ABBV-383<br>* Intravenous Infusion<br>* Other names: TNB-383B;|
| Experimental: Safety Expansion: ABBV-383 Expansion B<br>Participants will receive ABBV-383 expansion dose B during the approximately 2 year study duration. | Drug: ABBV-383<br>* Intravenous Infusion<br>* Other names: TNB-383B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose-Limiting Toxicities (DLT) | 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. | Up to 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieve Hematologic Complete Response (CR) | 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 International Amyloidosis Consensus Criteria. | Up to 3 Years | 
| Overall Hematologic Response (OHR) | OHR is defined as partial response (PR) + very good partial response (VGPR) + complete remission (CR), proportion of participants who achieved a PR or better, per the International Amyloidosis Consensus Criteria. | Up to 3 Years | 
| Time to Hematologic CR | Time to hematologic CR is defined as the time from first dose of study drug until CR, per the International Amyloidosis Consensus Criteria. | Up to 3 Years | 
| Duration of Hematologic CR | Duration of hematologic CR is defined as the time from CR until disease progression, per the International Amyloidosis Consensus Criteria. | Up to 3 Years | 
| Organ Response Rate (OrRR) | Organ response rate is defined as the time from first dose of study drug until to response in the heart kidney and liver, per the International Amyloidosis Consensus Criteria. | Up to 3 Years | 
| Time to Organ Response | Time to organ response is defined as the time from first dose of study drug until organ response, per the International Amyloidosis Consensus Criteria. | Up to 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunoglobulin Light Chain (AL) Amyloidosis, ABBV-383, TNB-383B