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



Status:Recruiting
Conditions:Hematology
Therapuetic Areas:Hematology
Healthy:No
Age Range:18 - Any
Updated:3/15/2019
Start Date:April 5, 2018
End Date:November 30, 2021
Contact:Wendy Currlin
Email:wendy.currlin@prothena.com
Phone:650-615-2145

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A Phase 1, Open-label, Dose Escalation Study of Intravenous PRX004 in Subjects With Amyloid Transthyretin (ATTR) Amyloidosis

A Phase 1, open-label study of intravenous (IV) PRX004 as a single agent in subjects with
hereditary amyloid transthyretin (hATTR) amyloidosis. The study will consist of 3 phases and
will enroll up to a total of 36 subjects. A 3+3 dose escalation component to determine the
safety, tolerability, PK, PD, and MTD. An expansion component in anticipated PRX004 RP2D
cohorts selected from the Dose Escalation Phase. An extended dosing component for eligible
subjects from the Dose Escalation or Expansion phases.

This Phase 1, open-label consists of 3 phases. The Dose Escalation Phase is a 3+3 dose
escalation component to determine the safety, tolerability, PK, PD, and MTD of IV PRX004 when
given as a single agent in up to 36 evaluable subjects with hATTR amyloidosis. The Expansion
Phase is an expansion component in anticipated PRX004 RP2D cohorts selected from the Dose
Escalation Phase (this may occur in addition to cohorts in which additional subjects were
added due to the observation of a dose-limiting [DLT] in the Escalation Phase). The Long-term
Extension (LTE) Phase is an extended dosing component for eligible subjects from the Dose
Escalation or Expansion phases.

The Dose Escalation Phase will follow a standard 3+3 design, in which cohorts of 3 to 6
subjects with hATTR amyloidosis will be enrolled at each dose level to receive IV PRX004 once
every 28 days, based on scheduling from Month 1-Day 1 for up to 3 doses. Each subject will
participate in only 1 dose escalation cohort. The starting dose of PRX004 will be 0.1 mg/kg.

Dose escalation will occur after the third evaluable subject in a cohort has completed the
first 28 days following the first administration of PRX004. Up to 6 dose levels of PRX004 may
be investigated (0.1, 0.3, 1, 3, 10, and 30 mg/kg) if tolerable. In the event the starting
dose of 0.1 mg/kg is not tolerated, the dose escalationwill be halted and the study stopped.

Each subject will receive a maximum of 3 infusions of PRX004 in the Dose Escalation Phase.
Subjects who complete the Month 3-Day 22 Visit in the Dose Escalation or Expansion phases may
be eligible to receive up to 15 additional PRX004 infusions in the LTE Phase.

Each subject will receive a maximum of 3 infusions of PRX004 in the Dose Escalation Phase.
Subjects who complete the Month 3-Day 22 Visit in the Dose Escalation or Expansion phases may
be eligible to receive up to 15 additional PRX004 infusions in the LTE Phase.

Subjects who completed the EOS Visit in the Dose Escalation Phase prior to implementation of
Protocol Amendment 2 may re-enter the study in the LTE Phase if they meet specific
inclusion/exclusion criteria.

Inclusion Criteria:

1. Age ≥18 years

2. Confirmed diagnosis of ATTR amyloidosis

3. Known TTR mutation

4. Subjects receiving concomitant tafamidis or diflunisal may enroll in the study
(providing the dose has been stable for the last 6 months)

5. Karnofsky Performance Status (KPS) score ≥60

6. 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

7. Subjects with cardiomyopathy must have an NT-proBNP ≥650 pg/mL and ≤5000 pg/mL (i.e.,
≥76.9 pmol/L and 591 pmol/L) or evidence of septal wall thickening >1.2 cm on
echocardiogram

8. 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 (eg, abdominal fat pad,
salivary gland), at the Investigator's discretion. Nerve biopsies are not required.

9. Polyneuropathy Disability (PND) Score ≤IIIB

10. Neuropathy Impairment Score (NIS) ≥5 and ≤130

Exclusion Criteria:

1. Amyloid light chain or other non-ATTR amyloidosis

2. Any past history of or present abuse of alcohol, diabetes, B12 or folate deficiencies,
autoimmune diseases, hereditary disorders other than TTR (e.g. Charcot Marie-Tooth),
uncontrolled hypothyroidism or other etiologies for the peripheral neuropathy

3. Received prior liver transplant

4. Planned liver transplant

5. mBMI ≤600 kg/m2 × g/L

6. New York Heart Association (NYHA) Functional Class III-IV

7. LVEF ≤45%

8. Uncontrolled symptomatic orthostatic hypotension

9. 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

10. 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

11. Hospitalized for heart failure within the 12 weeks prior to the first dose of study
drug

12. Treatment with patisiran or inotersen within 30 days or 5 half-lives whichever is
longer) prior to Month 1-Day 1
We found this trial at
10
sites
630 W 168th St
New York, New York
212-305-2862
Principal Investigator: Mathew Maurer
Columbia University Medical Center Situated on a 20-acre campus in Northern Manhattan and accounting for...
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800 Washington St
Boston, Massachusetts 02111
(617) 636-5000
Principal Investigator: Raymond Comenzo
Tufts Medical Center Tufts Medical Center is an internationally-respected academic medical center – a teaching...
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Boston, MA
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9500 Euclid Avenue
Cleveland, Ohio 44106
216.444.2200
Principal Investigator: Mazan Hanna, MD
Cleveland Clinic Cleveland Clinic is committed to principles as presented in the United Nations Global...
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Cleveland, OH
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Principal Investigator: Chafic Karam, MD
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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Portland, OR
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1428 Madison Ave
New York, New York 10029
(212) 241-6500
Principal Investigator: Peter Gorevic, MD
Icahn School of Medicine at Mount Sinai Icahn School of Medicine at Mount Sinai is...
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Philadelphia, Pennsylvania
Principal Investigator: Brian Drachman, MD
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Philadelphia, PA
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Porto, 40993
Principal Investigator: Ana Martins Silva
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Porto,
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Rochester, Minnesota 55905
Principal Investigator: Martha Grogan
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Rochester, MN
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Saint Louis, Missouri 63110
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Saint Louis, MO
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Stanford, California 94305
Principal Investigator: Ronald Witteles
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Stanford, CA
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