Clinical trial NCT06158854: 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
Official title: An Open-Label Phase 1b Study Evaluating the Safety and Efficacy of Etentamig (ABBV-383) in AL Amyloidosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Immunoglobulin Light Chain (AL) Amyloidosis
Keywords: Immunoglobulin Light Chain (AL) Amyloidosis
ABBV-383
TNB-383B
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2023-12-06
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Dose-Limiting Toxicities (DLT)
timeFrame: Up to 28 Days
Secondary outcomes:
measure: Percentage of Participants who Achieve Hematologic Complete Response (CR)
timeFrame: Up to 3 Years
measure: Overall Hematologic Response (OHR)
timeFrame: Up to 3 Years
measure: Time to Hematologic CR
timeFrame: Up to 3 Years
measure: Duration of Hematologic CR
timeFrame: Up to 3 Years
measure: Organ Response Rate (OrRR)
timeFrame: Up to 3 Years
measure: Time to Organ Response
timeFrame: Up to 3 Years
Other outcomes:
Locations:
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center - University of Miami /ID# 255856
state: Florida
city: Boston
country: United States
facility: Boston Medical Center /ID# 255066
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester /ID# 255258
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center /ID# 255068
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center-Koch Center /ID# 255073
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute /ID# 255074
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health /ID# 255851
state: North Carolina
city: Portland
country: United States
facility: Oregon Medical Research Center /ID# 255119
state: Oregon
city: Seattle
country: United States
facility: University of Washington /ID# 261581
state: Washington
city: Milwaukee
country: United States
facility: Wisconsin Medical Center /ID# 255836
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Hospital /ID# 255200
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital /ID# 255202
state: Queensland
city: Box Hill
country: Australia
facility: Box Hill Hospital /ID# 255199
state: Victoria
city: Limoges CEDEX 1
country: France
facility: CHU Limoges - Dupuytren 1 /ID# 255370
state: Franche-Comte
city: Toulouse
country: France
facility: CHU Toulouse - Hopital Rangueil /ID# 255377
state: Haute-Garonne
city: Athens
country: Greece
facility: Alexandra General Hospital /ID# 255542
state: Attiki
city: Bologna
country: Italy
facility: IRCCS AOU di Bologna Policlinico Sant Orsola Malpighi /ID# 255654
city: Nagoya shi
country: Japan
facility: Nagoya City University Hospital /ID# 256086
state: Aichi
city: Kumamoto shi
country: Japan
facility: Kumamoto University Hospital /ID# 262579
state: Kumamoto
city: Shibuya-ku
country: Japan
facility: Japanese Red Cross Medical Center /ID# 256083
state: Tokyo
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: