A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Immunoglobulin Light Chain (AL) Amyloidosis Receiving Etentamig (ABBV-383) as an Intravenous (IV) Infusion
- Conditions
- Immunoglobulin Light Chain (AL) Amyloidosis
- Interventions
- Drug: ABBV-383 (Etentamig)
- Registration Number
- NCT06158854
- Lead Sponsor
- AbbVie
- Brief Summary
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 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 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 76
- 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.
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Known history of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.
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Known allergic reaction, significant sensitivity, or intolerance to constituents of the study drugs (and excipients) and/or other products in the same class.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Escalation: ABBV-383 (etentamig) Dose A ABBV-383 (Etentamig) Participants will receive ABBV-383 (etentamig) dose A during the approximately 2 year study duration. Safety Expansion: ABBV-383 (etentamig) Expansion B ABBV-383 (Etentamig) Participants will receive ABBV-383 (etentamig) expansion dose B during the approximately 2 year study duration. Dose Escalation: ABBV-383 (etentamig) Dose B ABBV-383 (Etentamig) Participants will receive ABBV-383 (etentamig) dose B during the approximately 2 year study duration. Dose Escalation: ABBV-383 (etentamig) Dose C ABBV-383 (Etentamig) Participants will receive ABBV-383 (etentamig) dose C during the approximately 2 year study duration. Safety Expansion: ABBV-383 (etentamig) Expansion A ABBV-383 (Etentamig) Participants will receive ABBV-383 (etentamig) expansion dose A during the approximately 2 year study duration.
- Primary Outcome Measures
Name Time Method Number of Participants with Dose-Limiting Toxicities (DLT) 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.
- Secondary Outcome Measures
Name Time Method Duration of Hematologic CR Up to 3 Years Duration of hematologic CR is defined as the time from CR until disease progression, per the modified IACC.
Time to Hematologic CR Up to 3 Years Time to hematologic CR is defined as the time from first dose of study drug until CR, per the modified IACC.
Organ Response Rate (OrRR) Up to 3 Years 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 IACC.
Percentage of Participants who Achieve Hematologic Complete Response (CR) Up to 3 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).
Overall Hematologic Response (OHR) Up to 3 Years 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 modified IACC.
Time to Organ Response Up to 3 Years Time to organ response is defined as the time from first dose of study drug until organ response, per the IACC.
Trial Locations
- Locations (20)
Box Hill Hospital /ID# 255199
🇦🇺Box Hill, Victoria, Australia
CHU Limoges - Dupuytren 1 /ID# 255370
🇫🇷Limoges CEDEX 1, Franche-Comte, France
CHU Toulouse - Hopital Rangueil /ID# 255377
🇫🇷Toulouse, Haute-Garonne, France
Alexandra General Hospital /ID# 255542
🇬🇷Athens, Attiki, Greece
IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 255654
🇮🇹Bologna, Italy
Nagoya City University Hospital /ID# 256086
🇯🇵Nagoya shi, Aichi, Japan
Kumamoto University Hospital /ID# 262579
🇯🇵Kumamoto shi, Kumamoto, Japan
Japanese Red Cross Medical Center /ID# 256083
🇯🇵Shibuya-ku, Tokyo, Japan
Mayo Clinic - Rochester /ID# 255258
🇺🇸Rochester, Minnesota, United States
Boston Medical Center /ID# 255066
🇺🇸Boston, Massachusetts, United States
Sylvester Comprehensive Cancer Center - University of Miami /ID# 255856
🇺🇸Miami, Florida, United States
Columbia University Medical Center /ID# 255068
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 255073
🇺🇸New York, New York, United States
Levine Cancer Institute /ID# 255074
🇺🇸Charlotte, North Carolina, United States
Wake Forest Baptist Health /ID# 255851
🇺🇸Winston-Salem, North Carolina, United States
Oregon Medical Research Center /ID# 255119
🇺🇸Portland, Oregon, United States
University of Washington /ID# 261581
🇺🇸Seattle, Washington, United States
Wisconsin Medical Center /ID# 255836
🇺🇸Milwaukee, Wisconsin, United States
Westmead Hospital /ID# 255200
🇦🇺Westmead, New South Wales, Australia
Princess Alexandra Hospital /ID# 255202
🇦🇺Woolloongabba, Queensland, Australia