A Study of PRX004 in Subjects With Amyloid Transthyretin (ATTR) Amyloidosis
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|ClinicalTrials.gov Identifier: NCT03336580|
Recruitment Status : Not yet recruiting
First Posted : November 8, 2017
Last Update Posted : January 5, 2018
|Condition or disease||Intervention/treatment||Phase|
|Amyloid Transthyretin (ATTR) Amyloidosis||Drug: PRX004||Phase 1|
This study consists of the following:
A Phase 1, open-label, 3+3 dose escalation component to determine the safety, tolerability, PK, PD, and MTD of intravenous (IV) PRX004 when given as a single agent in 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.
The dose escalation component 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. A ±4 day visit window may be allowed for Months 2 and 3 Day 1 visits. Each subject will participate in only 1 dose escalation cohort. The starting dose of PRX004 will be 0.1 mg/kg.
Each cohort must include at least 2 of 3 (or 4 of 6) subjects with evidence of ATTR amyloidosis cardiac involvement and at least 1 subject with ATTR amyloidosis peripheral neuropathy involvement although it is recognized that subjects may have evidence of both manifestations. A single subject will be dosed at the initial PRX004 dose level of 0.1 mg/kg and observed for 7 days for tolerance to the dose before enrollment of an additional 2 subjects at the starting dose of 0.1 mg/kg may be considered. The first 3 subjects will be dosed at the initial PRX004 dose of 0.1 mg/kg and must complete the first 28 days following the first administration of PRX004 before dose escalation in subsequent cohorts of subjects may occur.
Each subsequent dose escalation cohort will follow the same dosing strategy; one subject will be enrolled at the new dose level and will be treated and observed for the first 7 days following treatment for tolerance to the dose before an additional 2 subjects may be treated at that dose level. Dose escalation in subsequent cohorts will occur after the third evaluable subject 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 addition, intermediate dose levels may be investigated. In the event the starting dose is not tolerated, the dose escalation will be halted and the study stopped.
Each subject will receive a maximum of 3 infusions of PRX004. Dosing beyond 3 infusions may be added in a subsequent protocol amendment after the availability of 6 month nonclinical toxicology study results.
Subjects who discontinue study drug before the third infusion should have an Early Termination from Study (ETS) Visit 30 (±5 days) after their final administration of study drug.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Dose Escalation Study|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1, Open-label, Dose Escalation Study of Intravenous PRX004 in Subjects With Amyloid Transthyretin (ATTR) Amyloidosis|
|Anticipated Study Start Date :||March 31, 2018|
|Estimated Primary Completion Date :||August 31, 2019|
|Estimated Study Completion Date :||December 31, 2019|
Experimental: 3+3 Cohort Study
This is a Phase 1 3+3 design Cohort Study
PRX004 is supplied as a sterile, lyophilized dosage form in 20 mL vials, each containing 250 mg of product.
- To determine the Maximum tolerated dose (MTD) of PRX004 in subjects with hATTR amyloidosis [ Time Frame: 18 months ]To determine the maximum tolerated dose (MTD) of PRX004 in subjects with hATTR amyloidosis. •
- Determine the recommended Phase 2 dose(s) RP2D[s] of PRX004 in subjects with hATTR amyloidosis [ Time Frame: 18 months ]To determine the recommended Phase 2 dose(s) (RP2D[s]) of PRX004 by evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PRX004 in subjects with hATTR amyloidosis
- To further characterise the safety,tolerability,PK and PD of the anticipated RP2D(s) of PRX004 in subjects with hATTR or wtATTR amyloidosis [ Time Frame: 18 months ]To further characterize the safety, tolerability, PK, and PD of the anticipated RP2D(s) of PRX004 in subjects with hATTR or wild type amyloid transthyretin (wtATTR) amyloidosis
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03336580
|Contact: Dimple Jashnanifirstname.lastname@example.org|
|Contact: Laura Maher||+353 1 236 email@example.com|