Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Written informed consent obtained from the subject prior to any trial-related procedure indicating that he/she understands the purpose of, and procedures required for the trial and is willing to participate in it
Male or female subjects aged ≥18 years (and < 85 years only for cohort 7) at the time of obtaining informed consent and with confirmed availability for the scheduled trial visits

Confirmed ATTR-Cardiomyopathy diagnosis established by:

Polarizing light microscopy of green birefringent material in Congo red-stained tissue specimens and confirmed diagnosis of ATTR amyloidosis by IHC or mass spectrometry OR
positive bone scintigraphy using either DPD, HMDP or PYP, with cardiac signal intensity indicative of ATTR-Cardiomyopathy (early phase imaging: cardiac mediastinum ratio > 1.21; late phase imaging: Perugini Grade 2 or 3) and absence of gammopathy (negative serum and urine immunofixation electrophoresis plus normal free light chain serum ratio). If a gammopathy is detected, diagnosis must be established based on tissue biopsy as indicated above

Known genotype as follows:

Known pathogenic TTR mutation for subjects with hereditary ATTR- Cardiomyopathy
Known negative genetic testing for a TTR mutation for subjects with sporadic, WT- ATTR-Cardiomyopathy

Chronic Heart Failure with all of the following characteristics:

LVEF ≥40%
LVWT ≥14 mm, measured by echocardiography
NT-proBNP level ≥600 pg/mL
Able to walk ≥150 meter in the 6-MWT
NYHA class III (applicable only for cohort 7)
No hospitalizations for cardiac disease for at least 30 calendar days prior to screening
General health status acceptable for a participation in a clinical trial with a Karnofsky Performance Status ≥60%
Stable pharmacological treatment of any other chronic condition for at least 30 calendar days prior to screening, with the exclusion of immunomodulatory and immunosuppressive treatments
ANC ≥1000 cells/mm³, platelet count ≥100,000 cells/mm³, and hemoglobin ≥10 g/dL
Women of childbearing potential must have a negative serum pregnancy test at screening and must agree to use highly effective physician-approved contraception from screening to 5 months after ending trial participation
Males must be surgically sterile or must agree to use highly effective physician-approved contraception throughout of the trial participation, and for 5 months after ending trial participation

Exclusion Criteria:

Amyloid light-chain amyloidosis or any other non ATTR amyloidosis
Heart failure corresponding to NYHA class IV
Uncontrolled hypertension with systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg confirmed by 3 measurements in supine position recorded with 5 minutes break in between the measurements
Hypotension with systolic pressure ≤ 90 mmHg or diastolic pressure ≤ 60 mmHg confirmed by 3 measurements in supine position recorded with 5 minutes break in between the measurements
NT-proBNP ≥6'000 pg/mL (NT-proBNP ≥8'500 pg/mL applicable only for cohort 7)
Heart failure not predominantly caused by ATTR-Cardiomyopathy
Any severe uncorrected valve disease

Chronic liver disease with liver function test abnormalities:

ALT and AST > 2.5 × ULN
Total bilirubin > 2 × ULN
Respiratory insufficiency requiring oxygen therapy
Renal insufficiency with eGFR < 30 mL/min/1.73 m2 using the CKD-EPI equation

Active malignancy with exception of the following:

Adequately treated basal cell carcinoma
Squamous cell carcinoma of the skin
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
Uncontrolled infection as per Investigator's judgement
Known HIV infection, seropositivity for HIV, hepatitis B and C as well as active hepatitis A
Autoimmune disease requiring immunosuppressive/modulating treatment in the last 2 years
History of organ transplantation or ventricular assist device
Polyneuropathy disability score > IIIA
Suspected or known intolerance/allergy to proteins or any components of the investigational medicinal product
Concomitant immunosuppressant therapy e.g., corticosteroids, prednisone, dexamethasone except as indicated in low dose (i.e., up to 10 mg prednisone or equivalent daily is allowed) for other medical conditions such as inhaled steroid for asthma
Use of the following drugs acting on TTR or ATTR: tolcapone, diflunisal, patisiran, inotersen, and long-term doxycycline, in the 30 calendar days prior to signing informed consent form. Tafamidis is permitted if it is given as standard of care in a stable dose for at least 30 calendar days prior to signing the informed consent form
Participation in another investigational clinical trial or intake of investigational drug within 30 calendar days before signing the informed consent form
Suspected or known drug or alcohol abuse
Serious psychiatric or any other medical condition (including laboratory abnormalities), which, in the opinion of the Investigator, makes the subject unsuitable for inclusion and puts the subject at an unacceptable risk
Subject is nursing or is considering becoming pregnant during the trial or in the 5 months after ending trial participation
Unwillingness or inability to adhere to the trial requirements
If subject is in any way dependent on Neurimmune AG or the principal Investigator or if the subject is accommodated in an establishment on judicial or administrative order
Employee or immediate family (spouse, parent, child or sibling, whether biological or legally adopted) of an employee of Neurimmune AG, the contract research organization or the trial site