Efficacy and Safety of VB-1953 Topical Gel in Non-Responder Acne Patients with Clindamycin-Resistant Cutibacterium acnes.
Acne Vulgaris
/ diagnosis
Administration, Topical
Adolescent
Adult
Anti-Bacterial Agents
/ administration & dosage
Clindamycin
/ pharmacology
Drug Resistance, Bacterial
/ drug effects
Female
Gels
/ administration & dosage
Humans
Male
Microbial Sensitivity Tests
Middle Aged
Organic Chemicals
/ administration & dosage
Propionibacterium acnes
/ drug effects
Prospective Studies
Young Adult
Journal
Drugs in R&D
ISSN: 1179-6901
Titre abrégé: Drugs R D
Pays: New Zealand
ID NLM: 100883647
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
pubmed:
31
3
2020
medline:
15
12
2020
entrez:
31
3
2020
Statut:
ppublish
Résumé
The emergence of resistant strains of Cutibacterium acnes can limit the efficacy of currently approved antibiotics for acne. VB-1953 is a next-generation antibiotic that exerts a bactericidal effect on resistant C. acnes. In this study, we investigated the safety, tolerability, and efficacy of VB-1953 topical gel in patients with moderate to severe acne having clindamycin-resistant C. acnes. An investigator-initiated, open label, single-arm clinical study was conducted in patients with moderate to severe facial acne vulgaris showing poor or no response to previous clindamycin treatment. Nineteen subjects were enrolled in the study based on laboratory screening for the presence of clindamycin-resistant C. acnes in acne swab samples collected from patients. VB-1953 2% gel was applied on the entire face twice daily over 12 weeks. The primary efficacy endpoints were absolute changes in inflammatory and noninflammatory lesion counts from baseline at week 12, while the secondary efficacy endpoint was the proportion of subjects achieving Investigator Global Assessment success (score of 0 or 1) or a grade 2 or higher improvement from baseline at week 12. The presence and severity of local skin reactions (erythema, edema, scaling/dryness, burning/stinging, pruritus) were evaluated for safety. Additionally, the detection and quantification of drug-resistant C. acnes strains were performed in the laboratory using acne swab samples collected from patients. The occurrence of treatment-emergent adverse events or changes in vital signs, physical examinations, and urinalysis for any of the patients during the course of the entire study were clinically insignificant. Topical application of 2% VB-1953 topical gel resulted in a significant reduction of mean absolute inflammatory and noninflammatory lesion counts by 53.1% and 52.2%, respectively (p < 0.0001 for both), with an Investigator Global Assessment success of 26.3% at week 12 compared with baseline. Resistant bacteria were reduced by (94.3 ± 1%; p < 0.05) within 12 weeks of treatment with VB-1953. These results indicate that VB-1953 topical gel can be a safe and effective therapy for moderate to severe acne with underlying resistant C. acnes in subjects who had not responded to previous antibiotic treatments.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
The emergence of resistant strains of Cutibacterium acnes can limit the efficacy of currently approved antibiotics for acne. VB-1953 is a next-generation antibiotic that exerts a bactericidal effect on resistant C. acnes. In this study, we investigated the safety, tolerability, and efficacy of VB-1953 topical gel in patients with moderate to severe acne having clindamycin-resistant C. acnes.
METHODS
METHODS
An investigator-initiated, open label, single-arm clinical study was conducted in patients with moderate to severe facial acne vulgaris showing poor or no response to previous clindamycin treatment. Nineteen subjects were enrolled in the study based on laboratory screening for the presence of clindamycin-resistant C. acnes in acne swab samples collected from patients. VB-1953 2% gel was applied on the entire face twice daily over 12 weeks. The primary efficacy endpoints were absolute changes in inflammatory and noninflammatory lesion counts from baseline at week 12, while the secondary efficacy endpoint was the proportion of subjects achieving Investigator Global Assessment success (score of 0 or 1) or a grade 2 or higher improvement from baseline at week 12. The presence and severity of local skin reactions (erythema, edema, scaling/dryness, burning/stinging, pruritus) were evaluated for safety. Additionally, the detection and quantification of drug-resistant C. acnes strains were performed in the laboratory using acne swab samples collected from patients.
RESULTS
RESULTS
The occurrence of treatment-emergent adverse events or changes in vital signs, physical examinations, and urinalysis for any of the patients during the course of the entire study were clinically insignificant. Topical application of 2% VB-1953 topical gel resulted in a significant reduction of mean absolute inflammatory and noninflammatory lesion counts by 53.1% and 52.2%, respectively (p < 0.0001 for both), with an Investigator Global Assessment success of 26.3% at week 12 compared with baseline. Resistant bacteria were reduced by (94.3 ± 1%; p < 0.05) within 12 weeks of treatment with VB-1953.
CONCLUSION
CONCLUSIONS
These results indicate that VB-1953 topical gel can be a safe and effective therapy for moderate to severe acne with underlying resistant C. acnes in subjects who had not responded to previous antibiotic treatments.
Identifiants
pubmed: 32222937
doi: 10.1007/s40268-020-00299-z
pii: 10.1007/s40268-020-00299-z
pmc: PMC7221013
doi:
Substances chimiques
Anti-Bacterial Agents
0
Gels
0
Organic Chemicals
0
VB-1953
0
Clindamycin
3U02EL437C
Types de publication
Clinical Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
95-104Références
J Am Acad Dermatol. 2007 Apr;56(4):651-63
pubmed: 17276540
J Invest Dermatol. 2014 Nov;134(11):2747-2756
pubmed: 24820890
BMJ. 2002 Aug 31;325(7362):475-9
pubmed: 12202330
J Dermatol Sci. 2009 Nov;56(2):106-12
pubmed: 19726162
Br J Dermatol. 2001 Feb;144(2):339-46
pubmed: 11251569
Dermatol Ther. 2016 Nov;29(6):451-454
pubmed: 27424878
Arch Dermatol Res. 2010 Dec;302(10):745-56
pubmed: 20697725
N Engl J Med. 1997 Apr 17;336(16):1156-62
pubmed: 9099661
Clin Infect Dis. 2001 Mar 15;32 Suppl 1:S9-S15
pubmed: 11249823
Life Sci. 2015 Oct 15;139:123-31
pubmed: 26341693
Br J Dermatol. 2004 Mar;150(3):421-8
pubmed: 15030323
Br J Dermatol. 1994 Mar;130(3):329-36
pubmed: 8148274
Infect Immun. 1995 Aug;63(8):3158-65
pubmed: 7542639
Expert Rev Anti Infect Ther. 2015 Jul;13(7):883-96
pubmed: 26025191
Expert Opin Emerg Drugs. 2015 Mar;20(1):91-101
pubmed: 25474485
Br J Dermatol. 1984 Jul;111(1):83-92
pubmed: 6234917
Anaerobe. 2015 Feb;31:50-4
pubmed: 25451716
Antimicrob Agents Chemother. 1998 Jul;42(7):1702-5
pubmed: 9661007
Semin Cutan Med Surg. 2016 Jun;35(2):62-7
pubmed: 27416310
J Am Acad Dermatol. 1991 Oct;25(4):674-81
pubmed: 1838749
J Antimicrob Chemother. 2002 Jan;49(1):165-8
pubmed: 11751782
Br J Dermatol. 2005 Aug;153(2):395-403
pubmed: 16086756
Biotechniques. 2002 Apr;32(4):940-4, 946-9
pubmed: 11962616
J Mol Med (Berl). 2006 Jan;84(1):75-87
pubmed: 16388388
Br J Dermatol. 2013 Mar;168(3):474-85
pubmed: 23210645
Clin Exp Dermatol. 1981 Sep;6(5):461-9
pubmed: 6459196
J Am Acad Dermatol. 1983 Jan;8(1):41-5
pubmed: 6219134
Nucleic Acids Res. 1992 Sep 25;20(18):4717-20
pubmed: 1383931
Clin Drug Investig. 2020 Mar;40(3):259-268
pubmed: 31927743
J Infect Chemother. 2009 Jun;15(3):168-73
pubmed: 19554401
Eur J Dermatol. 2006 Jan-Feb;16(1):48-55
pubmed: 16436342
Br J Dermatol. 2015 Jul;172 Suppl 1:3-12
pubmed: 25597339
J Clin Aesthet Dermatol. 2011 May;4(5):22-6
pubmed: 21607190
J Invest Dermatol. 1992 Jun;98(6):895-901
pubmed: 1534342
Eur J Dermatol. 2014 Mar-Apr;24(2):201-9
pubmed: 24704684
J Eur Acad Dermatol Venereol. 2012 Feb;26 Suppl 1:1-29
pubmed: 22356611
J Immunol. 2002 Aug 1;169(3):1535-41
pubmed: 12133981
Sex Transm Infect. 2012 Oct;88(6):470-4
pubmed: 22611234
Infection. 2005 Dec;33 Suppl 2:55-70
pubmed: 16518713
J Am Acad Dermatol. 2009 May;60(5 Suppl):S1-50
pubmed: 19376456
Int J Dermatol. 1986 Dec;25(10):664-7
pubmed: 2948929
J Am Acad Dermatol. 2016 May;74(5):945-73.e33
pubmed: 26897386
Br J Dermatol. 2002 May;146(5):840-8
pubmed: 12000382
Arch Dermatol Res. 2010 Aug;302(6):429-33
pubmed: 20043171
PLoS One. 2012;7(7):e41480
pubmed: 22859988
Antimicrob Agents Chemother. 2003 Dec;47(12):3704-7
pubmed: 14638469
J Dermatol Sci. 2013 Feb;69(2):122-31
pubmed: 23178030
Nat Rev Dis Primers. 2015 Sep 17;1:15029
pubmed: 27189872
Nature. 2001 Oct 25;413(6858):814-21
pubmed: 11677599
Antimicrob Agents Chemother. 1997 May;41(5):1162-5
pubmed: 9145890
J Appl Microbiol. 2015 Jun;118(6):1418-25
pubmed: 25766481