A Study of PRX004 in Subjects With Amyloid Transthyretin (ATTR) Amyloidosis


About this study

A Phase 1, open-label, 3+3 dose escalation component to determine the safety, tolerability, PK, PD, and MTD of IV PRX004 when given as a single agent to up to 36 subjects with hATTR amyloidosis An expansion component in up to 2 anticipated PRX004 RP2D cohorts selected from dose escalation (up to an additional 3 subjects in each expanded cohort for up to 6 evaluable subjects total in each expanded cohort; an evaluable subject is defined as a subject who has completed the first 28 days following the first administration of PRX004 or who discontinued within 28 days due to study drug related toxicity). Subjects with wtATTR amyloidosis may be enrolled as part of the expansion component.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age ≥18 years old.
  • Ability to understand and willingness to sign an informed consent form (ICF) prior to initiation of any study procedures.
  • Diagnosis of amyloidosis determined by polarizing light microscopy of green birefringent material in Congo Red-stained tissue specimens; and confirmed diagnosis of ATTR amyloidosis by immunohistochemistry, mass spectrometry, documentation of an ATTR mutation by gene sequencing, or 99m technetium-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scans and/or technetium pyrophosphate (PYP) SPECT cardiac imaging. If scintigraphy is used for diagnosis then the grade must be 2 or greater, indicative of ATTR-CM (Gillmore, 2016).
  • Known TTR mutation.
  • Patients receiving concomitant tafamidis or diflunisal may enroll in the study, providing the dose has been stable for the last 6 months.
  • Karnofsky Performance Status (KPS) ≥60%.
  • Adequate organ function, including all of the following:
    • Adequate bone marrow reserve, defined as the following: absolute neutrophil count ≥1.0 × 109/L; platelet count ≥100 × 109/L; hemoglobin ≥10 g/dL;
    • Hepatic: total bilirubin ≤2 × upper limit of normal (ULN), transaminases (aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]) ≤3 × ULN; alkaline phosphatase ≤5 × ULN;
    • Renal: estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2.
  • If currently receiving a diuretic, must have been on a stable dose for at least 4 weeks prior to the first dose of study drug.
  • Systolic blood pressure ≥90 mmHg and ≤180 mmHg.
  • Subjects with cardiomyopathy must have an NT-proBNP ≥650 pg/mL and ≤5000 pg/mL (ie, ≥76.9 pmol/L and ≤591 pmol/L) or evidence of septal wall thickening >1.2 cm on echocardiogram.
  • Must have a biopsy unless data are available from a previous one. The biopsy may be taken from any tissue or organ affected by ATTR amyloidosis (i.e., skin, lip, abdominal fat pad, salivary gland), at the Investigator’s discretion. Nerve biopsies are not required.
  • Women of childbearing potential (WOCBP) must have 2 negative pregnancy tests during Screening, the second within 24 hours prior to the first administration of study drug and must agree to use highly effective physician-approved contraception (Appendix 1) from Screening to 90 days following the last study drug administration.
  • Male subjects must be surgically sterile or must agree to use highly effective physician-approved contraception (Appendix 1) from Screening to 90 days following the last study drug administration.
  • Polyneuropathy Disability (PND) Score ≤IIIB (Appendix 5).
  • NIS ≥5 and ≤130.

Exclusion Criteria

  • Amyloid light chain or other non-ATTR amyloidosis.
  • Any past history of or present abuse of alcohol, diabetes, B12 or folate deficiencies, autoimmune diseases, hereditary disorders other than TTR (i.e., Charcot-Marie-Tooth), uncontrolled hypothyroidism, or other etiologies for the peripheral neuropathy.
  • Received prior liver transplant.
  • Planned liver transplant during the study.
  • mBMI ≤600 kg/m2 × g/L.
  • New York Heart Association (NYHA) Functional Class III-IV (Appendix 2).
  • LVEF ≤45%.
  • Uncontrolled symptomatic orthostatic hypotension.
  • Myocardial infarction, unstable or uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, within 6 months prior to the first dose of study drug.
  • Any history of clinically significant sinus pauses on ECG.
  • Sinus pauses >3 seconds in the day or sinus pauses >5 seconds at night during the 48-hour pre-dose cardiac monitoring (i.e., prior to first dose of study drug).
  • Arrhythmia requiring treatment diagnosed during the 48-hour pre-dose cardiac monitoring (i.e., prior to first dose of study drug).
    • Note: subject could be reconsidered for entry into the study if appropriate treatment is obtained.
  • Hospitalized for heart failure within the 12 weeks prior to the first dose of study drug.
  • Uncontrolled infection, or active malignancy with the exception of the following:
    • Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer;
    • Low risk prostate cancer with Gleason score <7 and prostate specific antigen <10 mg/mL;
    • Any other cancer from which the subject has been disease-free for ≥2 years.
  • Clinically significant pleural effusion per Investigator (i.e., presence of pleural effusion ≥30% in either hemithorax).
  • History of Grade ≥3 hypersensitivity-associated AEs or hypersensitivities to other mAbs or the excipients found in the PRX004 formulation.
  • Known HIV infection or known hepatitis B or C virus carrier.
  • Women who are pregnant or breastfeeding.
  • Treatment with an investigational agent within 30 days or 5 half-lives (whichever is longer) prior to Month 1-Day 1.
  • Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the Investigator unacceptably increase the subject’s risk by participating in the study.
  • Treatment with patisiran or inotersen within 30 days or 5 half-lives (whichever is longer) prior to Month 1-Day 1.



Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Martha Grogan, M.D.

Closed for enrollment

More information


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