Refer a Patient

Do You Have a Patient with Transthyretin Amyloid Cardiomyopathy (ATTR-CM) Who May Be Interested in the DepleTTR-CM Study?

About the DepleTTR-CM Study

The purpose of the DepleTTR-CM Study is to evaluate the safety and efficacy of an amyloid depleter investigational medication (ALXN2220) compared to placebo in adult participants with advanced ATTR-CM.

Study Objectives

The primary objectives of this study will be:

To assess the efficacy of ALXN2220 in the treatment of adult participants with ATTR-CM by evaluating the difference between the ALXN2220 and placebo as assessed by the combined endpoint of all-cause mortality (ACM) and the cumulative frequency of cardiovascular (CV) clinical events

To assess the effects of ALXN2220 on health-based quality of life (QoL) as measured by the change from baseline in Kansas City Cardiomyopathy Questionnaire-Overall Score (KCCQ-OS)

Study Design

The DepleTTR-CM Study is a phase 3, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of ALXN2220. Participants will be randomized in a 2:1 ratio to receive either the investigational medication or placebo, which will be administered once every 4 weeks via intravenous (IV) infusion.

Participation will last approximately 2.5–4.5 years and consists of a screening period (35 days), a treatment period (2–4 years), and a safety follow-up period (4 months). Participants who complete the treatment period may be eligible to enroll in an open-label extension study, during which all participants will receive the investigational medication.

Key Inclusion Criteria

Male or female ≥ 18 to ≤ 90 years of age at time of randomization
Centrally confirmed diagnosis of ATTR-CM with either wild-type TTR or a variant TTR genotype based on:
- Evidence of cardiac amyloidosis by echocardiography or cMRI and 1 of the following:
  - Endomyocardial or extra-cardiac biopsy with confirmatory TTR amyloid typing by either mass spectrometry, immunoelectron microscopy, or immunohistochemistry, or
  - Grade 2 or 3 cardiac uptake on planar 99mTc scintigraphy (99mTc DPD, 99mTc PYP, or 99mTc HMDP) in the absence of monoclonal gammopathy, or
  - Grade 2 or 3 cardiac uptake on 99mTc scintigraphy (99mTc DPD, 99mTc PYP, or 99mTc HMDP) AND confirmatory TTR amyloid typing by either immunohistochemistry or mass spectrometry in non-cardiac tissue in the presence of monoclonal gammopathy
Willing to be genetically tested for mutations in the TTR gene during screening, if genetic testing was not previously performed or if genetic results are not available
End-diastolic interventricular septal wall thickness ≥ 11 mm for women or ≥ 12 mm for men on echocardiography measured at screening
NT-proBNP > 2,000 pg/mL measured by a central laboratory at screening

Key Exclusion Criteria

LVEF less than 30% on echocardiography measured at a central laboratory
Uncontrolled clinically significant cardiac arrhythmia, per investigator’s assessment
Known leptomeningeal amyloidosis
Known light chain (AL) or secondary amyloidosis (AA), or any other form of systemic amyloidosis
History of multiple myeloma
Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy primarily due to hypertension, valvular heart disease, or ischemic heart disease per investigator’s assessment
Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months prior of screening
Uncontrolled hypertension (average resting systolic [BP] > 160 mmHG or diastolic BP > 100 mmHG at screening)
Prior treatment with an ATTR amyloid depleter (i.e., monoclonal anti-ATTR antibody), approved or in clinical development

Additional eligibility criteria apply.

DepleTTR-CM Study Research Sites

If you have a patient who may be interested in participating and you think may qualify, refer them to this study website to take the prescreening questionnaire to determine eligibility.