PMID- 31945197
OWN - NLM
STAT- MEDLINE
DCOM- 20201013
LR  - 20210110
IS  - 1520-6777 (Electronic)
IS  - 0733-2467 (Print)
IS  - 0733-2467 (Linking)
VI  - 39
IP  - 2
DP  - 2020 Feb
TI  - Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer 
      by intravesical instillation or direct injection into the bladder wall in female 
      participants with idiopathic (non-neurogenic) overactive bladder syndrome and 
      detrusor overactivity from two double-blind, imbalanced, placebo-controlled 
      randomized phase 1 trials.
PG  - 744-753
LID - 10.1002/nau.24272 [doi]
AB  - AIMS: Two phase 1 trials were performed in healthy women with the overactive 
      bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity 
      (DO), with the aim to demonstrate the safety and potential efficacy of URO-902, 
      which comprises a gene therapy plasmid vector expressing the human big potassium 
      channel alpha subunit. METHODS: ION-02 (intravesical instillation) and ION-03 (direct 
      injection) were double-blind, placebo-controlled, multicenter studies without 
      overlap in enrollment between studies. Active doses were administered and 
      evaluated sequentially (lowest dose first) for safety. ION-02 participants 
      received either 5000 microg or 10 000 microg URO-902, or placebo. ION-03 participants 
      received either 16 000 or 24 000 microg URO-902, or placebo, injected directly into 
      the bladder wall using cystoscopy. Primary outcome variables were safety 
      parameters occurring subsequent to URO-902 administration; secondary efficacy 
      variables also were evaluated. RESULTS: Among the safety outcomes, there were no 
      dose-limiting toxicities or significant adverse events (AEs) preventing dose 
      escalation during either trial, and no participants withdrew due to AEs. For 
      efficacy, in ION-02 (N = 21), involuntary detrusor contractions on urodynamics at 
      24 weeks in patients receiving URO-902 (P < .0508 vs placebo) and mean urgency 
      incontinence episodes in the 5000 microg group (P = .0812 vs placebo) each showed a 
      downward trend. In ION-03 (N = 13), significant reduction versus placebo in 
      urgency episodes (16 000 microg, P = .036; 24 000 microg, P = .046) and number of voids 
      (16 000 microg, -2.16, P = .044; 24 000 microg, -2.73, P = .047) were observed 1 week 
      after injection. CONCLUSION: Promising safety and efficacy results in these 
      preliminary phase 1 studies suggest gene transfer may be a promising therapy for 
      OAB/DO, warranting further investigation.
CI  - (c) 2020 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, 
      Inc.
FAU - Rovner, Eric
AU  - Rovner E
AUID- ORCID: 0000-0003-3950-8752
AD  - Department of Urology, Medical University of South Carolina, Charleston, South 
      Carolina.
FAU - Chai, Toby C
AU  - Chai TC
AUID- ORCID: 0000-0002-8189-9518
AD  - Department of Urology, Boston University School of Medicine, Boston, 
      Massachusetts.
FAU - Jacobs, Sharon
AU  - Jacobs S
AD  - Ion Channel Innovations, LLC, New York, New York.
FAU - Christ, George
AU  - Christ G
AD  - Department of Orthopaedics, University of Virginia Medical School, 
      Charlottesville, Virginia.
FAU - Andersson, Karl-Erik
AU  - Andersson KE
AD  - Department of Urology, Wake Forest School of Medicine, Winston-Salem, North 
      Carolina.
FAU - Efros, Mitchell
AU  - Efros M
AD  - Accumed Research Associates, Garden City, New York.
FAU - Nitti, Victor
AU  - Nitti V
AD  - Departments of Urology and Obstetrics and Gynecology, David Geffen School of 
      Medicine at UCLA, Los Angeles, California.
FAU - Davies, Kelvin
AU  - Davies K
AD  - Department of Urology, Albert Einstein College of Medicine, New York, New York.
FAU - McCullough, Andrew R
AU  - McCullough AR
AD  - Department of Urology, Tufts University School of Medicine, Boston, 
      Massachusetts.
FAU - Melman, Arnold
AU  - Melman A
AUID- ORCID: 0000-0002-4213-9794
AD  - Department of Urology, Albert Einstein College of Medicine, New York, New York.
LA  - eng
GR  - R44 DK093279/DK/NIDDK NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200116
PL  - United States
TA  - Neurourol Urodyn
JT  - Neurourology and urodynamics
JID - 8303326
RN  - 0 (KCNMA1 protein, human)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channel alpha Subunits)
RN  - 9007-49-2 (DNA)
SB  - IM
CIN - J Urol. 2020 Oct;204(4):884-885. PMID: 32715915
MH  - Administration, Intravesical
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cystoscopy
MH  - DNA/administration & dosage/therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Genetic Therapy/adverse effects/*methods
MH  - Humans
MH  - Large-Conductance Calcium-Activated Potassium Channel alpha 
      Subunits/genetics/therapeutic use
MH  - Middle Aged
MH  - Patient Safety
MH  - Treatment Outcome
MH  - Urinary Bladder, Overactive/*therapy
MH  - Urodynamics
PMC - PMC7028015
OTO - NOTNLM
OT  - BK channel
OT  - gene therapy
OT  - incontinence
OT  - urinary urgency
EDAT- 2020/01/17 06:00
MHDA- 2020/10/21 06:00
PMCR- 2020/02/18
CRDT- 2020/01/17 06:00
PHST- 2019/09/12 00:00 [received]
PHST- 2019/12/25 00:00 [accepted]
PHST- 2020/01/17 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2020/01/17 06:00 [entrez]
PHST- 2020/02/18 00:00 [pmc-release]
AID - NAU24272 [pii]
AID - 10.1002/nau.24272 [doi]
PST - ppublish
SO  - Neurourol Urodyn. 2020 Feb;39(2):744-753. doi: 10.1002/nau.24272. Epub 2020 Jan 
      16.