PMID- 33278328
OWN - NLM
STAT- MEDLINE
DCOM- 20220103
LR  - 20220103
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 14
IP  - 3
DP  - 2021 May
TI  - A Randomized Phase I Study to Evaluate the Safety, Tolerability, and 
      Pharmacokinetics of Recombinant Erwinia Asparaginase (JZP-458) in Healthy Adult 
      Volunteers.
PG  - 870-879
LID - 10.1111/cts.12947 [doi]
AB  - L-asparaginase has been an important component of acute lymphoblastic leukemia 
      (ALL) therapy for over 40 years, and is standard therapy during ALL induction and 
      consolidation treatment. L-asparaginases are immunogenic and can induce 
      hypersensitivity reactions; inability to receive asparaginase has been associated 
      with poor patient outcomes. There are L-asparaginases of varied bacterial 
      origins, with the most commonly used being Escherichia coli (E. coli); therefore, 
      to ensure that patients who develop hypersensitivity to E. coli-derived 
      asparaginases receive an adequate therapeutic course, alternative preparations 
      are warranted. JZP-458 is a recombinant Erwinia asparaginase produced using a 
      novel Pseudomonas fluorescens expression platform that yields an enzyme with no 
      immunologic cross-reactivity to E. coli-derived asparaginases. To evaluate the 
      safety, tolerability, and pharmacokinetics (PK) of a single dose of JZP-458, a 
      randomized, single-center, open-label, phase I study was conducted with JZP-458 
      given via i.m. injection or i.v. infusion to healthy adult volunteers. At the 
      highest doses tested for each route of administration (i.e., 25 mg/m(2) i.m. and 
      37.5 mg/m(2) i.v.), JZP-458 achieved serum asparaginase activity (SAA) levels 
      >/= 0.1 IU/mL at 72 hours postdose for 100% of volunteers. Bioavailability for i.m. 
      JZP-458 was estimated at 36.8% based on SAA data. All dose levels were 
      well-tolerated, with no unanticipated adverse events (AEs), no serious AEs, and 
      no grade 3 or higher AEs. Based on PK and safety data, the recommended JZP-458 
      starting dose for the pivotal phase II/III study in adult and pediatric patients 
      is 25 mg/m(2) i.m. and 37.5 mg/m(2) i.v. on a Monday/Wednesday/Friday dosing 
      schedule.
CI  - (c) 2020 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals LLC on behalf of the American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Lin, Tong
AU  - Lin T
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
FAU - Hernandez-Illas, Martha
AU  - Hernandez-Illas M
AD  - QPS Miami Research Associates (Miami Clinical Research), Miami, Florida, USA.
FAU - Rey, Andres
AU  - Rey A
AD  - QPS Miami Research Associates (Miami Clinical Research), Miami, Florida, USA.
FAU - Jenkins, Jack
AU  - Jenkins J
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
FAU - Chandula, Reddy
AU  - Chandula R
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
FAU - Silverman, Jeffrey A
AU  - Silverman JA
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
FAU - Choi, Mi Rim
AU  - Choi MR
AD  - Jazz Pharmaceuticals, Palo Alto, California, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210323
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
RN  - 0 (Bacterial Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.5.1.1 (Asparaginase)
SB  - IM
MH  - Adult
MH  - Asparaginase/administration & dosage/*adverse effects/immunology/pharmacokinetics
MH  - Bacterial Proteins/administration & dosage/*adverse 
      effects/immunology/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Erwinia/*enzymology
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Intramuscular
MH  - Male
MH  - Middle Aged
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy
MH  - Recombinant Proteins/administration & dosage/adverse 
      effects/immunology/pharmacokinetics
PMC - PMC8212713
COIS- T.L. is an employee of and holds stock ownership and/or stock options in Jazz 
      Pharmaceuticals. M.H.-I. is an employee of QPS Miami Research Associates. A.R. is 
      an employee of QPS Miami Research Associates. J.J. is a contract employee of Jazz 
      Pharmaceuticals. R.C. is an employee of and holds stock ownership and/or stock 
      options in Jazz Pharmaceuticals. J.A.S. is an employee of and holds stock 
      ownership and/or stock options in Jazz Pharmaceuticals. M.R.C. is an employee of 
      and holds stock ownership and/or stock options in Jazz Pharmaceuticals.
EDAT- 2020/12/06 06:00
MHDA- 2022/01/04 06:00
PMCR- 2021/05/01
CRDT- 2020/12/05 17:11
PHST- 2020/07/14 00:00 [received]
PHST- 2020/11/13 00:00 [accepted]
PHST- 2020/12/06 06:00 [pubmed]
PHST- 2022/01/04 06:00 [medline]
PHST- 2020/12/05 17:11 [entrez]
PHST- 2021/05/01 00:00 [pmc-release]
AID - CTS12947 [pii]
AID - 10.1111/cts.12947 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2021 May;14(3):870-879. doi: 10.1111/cts.12947. Epub 2021 Mar 
      23.