Study Summary
ABBV-383: 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.

Who is eligible for the trial?
Patients with relapsed or refractory systemic AL amyloidosis who have previously been treated with bortezomib and daratumumab.

Does every patient receive the actual trial drug?
All patients receive ABBV-383.

How is the drug administered?
After an initial dose step up phase ABBV-383 is given as a subcutaneous injection every 28 days.

How long does the trial go for?
The treatment continues for 2 years in an estimated 76 patients. The trial will continue to watch the response in patients for a number of years after the treatment finished.

Key inclusion criteria:

1. 1. Diagnosis of primary systemic immunoglobulin light chain (AL) amyloidosis.
   2. Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
   3. Have at least 1 organ historically impacted by AL amyloidosis.
   4. dFLC Cutoff either ≥50 mg/L or High-risk dFLC progression after immediate prior line of therapy defined as meeting all of the following criteria:
      • >20 mg/L
      • >20% of baseline value before initiation of prior therapy
      • >50% of nadir at best response to prior therapy
   5. Cardiac Risk Stage: Patients considered AL amyloidosis cardiac risk stage 1, 2, or 3a, or considered cardiac risk stage 3b with stable cardiac function and biomarkers for 3 months prior to dosing with no cardiac-related hospitalizations within 3 months and no changes to diuretic regimen within 21 days of first dose of study treatment.
   6. Has previously been exposed to a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody.

Key exclusion criteria:

Subjects must meet none of the following criteria:

1. Known history of clinically significant (per investigator’s judgment) drug or alcohol abuse within the last 6 months.
2. Known allergic reaction, significant sensitivity, or intolerance to constituents of the study drugs (and excipients) and/or other products in the same class.
3. Participant has the following conditions:
   1. Other non-AL amyloid disease;
   2. 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);
   3. Active plasma cell leukemia (i.e., either 20% of peripheral white blood cells or > 2.0 × 109/L circulating plasma cells by standard differential);
   4. Waldenström’s macroglobulinemia;
   5. Acute diffuse infiltrative pneumopathy;
   6. Major surgery within 28 days prior first dose or planned during study participation;
   7. History of organ transplant requiring continued use of immunosuppressants;
   8. Acute infections within 14 days prior first dose requiring parenteral therapy (antibiotic, antifungal, or antiviral);
   9. 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.

For more information, please contact one of the three recruiting centres in Australia, or USE THIS LINK

Sites

New South Wales

Queensland

Victoria