Why Is the AFFIRM-AL Clinical Trial Being Conducted?

A post hoc analysis from VITAL, a Phase 3 clinical trial in newly diagnosed patients with AL amyloidosis, suggests that the investigational monoclonal antibody birtamimab may have a significant survival benefit in the subgroup of patients with Mayo Stage IV disease.1 This result is being confirmed in AFFIRM-AL.

What Is AFFIRM-AL and What Is Its Objective?

AFFIRM-AL is a confirmatory global Phase 3, randomized, placebo-controlled efficacy and safety clinical trial that will evaluate birtamimab compared with placebo, in combination with standard-of-care chemotherapy, in newly diagnosed Mayo Stage IV AL amyloidosis patients by assessing time to all-cause mortality.

Who Can Enroll in AFFIRM-AL?

Newly diagnosed and treatment-naïve patients with a confirmed diagnosis of Mayo 2012 Stage IV AL amyloidosis with cardiac involvement, in accordance with the inclusion and exclusion criteria of this clinical trial.

Which Efficacy Endpoints Will Be Assessed?

The primary endpoint is time to all-cause mortality. Secondary endpoints include change from baseline to month 9 in physical functioning (6MWT distance) and in quality of life (SF-36v2 PCS score).

Where Is AFFIRM-AL Being Conducted?

The clinical trial is being conducted at centers across North America, Europe, the Middle East, and Asia-Pacific.

Which Sites Are Currently Enrolling?

For more information on the AFFIRM-AL sites that are open for enrollment, please see ClinicalTrials.gov or contact AFFIRM-ALClinicalTrials@prothena.com

AFFIRM-AL is currently enrolling.

If you have a patient who may be suitable for enrollment in AFFIRM-AL, please visit ClinicalTrials.gov or contact AFFIRM-ALClinicalTrials@prothena.com

Patients can get more information on AFFIRM-AL by visiting https://affirm-al.com

Confirmatory Global Phase 3 Study Design

Key Inclusion Criteria

  • Newly diagnosed and treatment naïve
  • Confirmed diagnosis of AL amyloidosis with cardiac involvement
  • Mayo Stage IV

Key Exclusion Criteria

  • NT-proBNP >8500 pg/mL
  • Autologous stem cell transplant

Randomize 2:1

N≈220

Birtamimab

(IV q28d) + SoC*

N≈147

Placebo

(IV q28d) + SoC*

N≈73

Primary Endpoint

Time to all-cause morality

SPA agreement with FDA on primary endpoint at a significance level of 0.10

Secondary Endpoints

6MWT

SF-36v2 PCS

Interim analysis when ~50% of events have occurred

Trial is currently enrolling

*SoC consists of a bortezomib-containing chemotherapy regimen. SoC may also include daratumumab but daratumumab must be initiated at randomization.3

6MWT, 6-minute walk test; AL, light chain; FDA, U.S. Food and Drug Administration; IV, intravenous; NT-ProBNP, N-terminal pro-brain natriuretic peptide; q28d, every 28 days; SF-36v2 PCS, 36-Item Short-Form Health Survey, version 2.0 Physical Component Summary; SoC, standard of care; SPA, Special Protocol Assessment.

  1. Gertz MA, et al. Blood. 2023;142:1208–1218.
  2. AFFIRM-AL Amyloidosis Trial; NCT04973137. Accessed May 2024. https://clinicaltrials.gov/study/NCT04973137.
  3. Wechalekar AD, et al. Amyloid. 2023;30:3–17.