Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-naïve infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial].
Adolescent
Adult
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Double-Blind Method
Gambia
Humans
Infant
Measles
/ prevention & control
Measles Vaccine
/ adverse effects
Randomized Controlled Trials as Topic
Rubella
/ prevention & control
Rubella Vaccine
/ adverse effects
Young Adult
Age de-escalation
Double dummy
Measles vaccine
Microarray patch
Microneedle
Microneedle patch
Phase 1 clinical trial
Phase 2 clinical trial
Rubella vaccine
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
14 Sep 2022
14 Sep 2022
Historique:
received:
17
02
2022
accepted:
24
06
2022
entrez:
14
9
2022
pubmed:
15
9
2022
medline:
17
9
2022
Statut:
epublish
Résumé
New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. Pan-African Clinical Trials Registry 202008836432905 . gov NCT04394689.
Sections du résumé
BACKGROUND
BACKGROUND
New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants.
METHODS
METHODS
This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee.
DISCUSSION
CONCLUSIONS
This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination.
TRIAL REGISTRATION
BACKGROUND
Pan-African Clinical Trials Registry 202008836432905 .
CLINICALTRIALS
RESULTS
gov NCT04394689.
Identifiants
pubmed: 36104719
doi: 10.1186/s13063-022-06493-5
pii: 10.1186/s13063-022-06493-5
pmc: PMC9472726
doi:
Substances chimiques
Measles Vaccine
0
Rubella Vaccine
0
Banques de données
ClinicalTrials.gov
['NCT04394689']
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
775Subventions
Organisme : Medical Research Council
ID : MC_UU_00031/7
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Vaccine. 2015 Sep 8;33(37):4712-8
pubmed: 25770786
Stat Methods Med Res. 1993;2(1):23-41
pubmed: 8261248
Wkly Epidemiol Rec. ;92(17):205-27
pubmed: 28459148
Wkly Epidemiol Rec. 2013 Dec 6;88(49):521-7
pubmed: 24367837
Vaccine. 2014 Nov 28;32(50):6791-7
pubmed: 25446830
Clin Diagn Lab Immunol. 2000 Nov;7(6):964-6
pubmed: 11063507
MMWR Morb Mortal Wkly Rep. 2017 Oct 27;66(42):1148-1153
pubmed: 29073125
Drugs R D. 2016 Dec;16(4):327-338
pubmed: 27696306
Lancet. 1982 Oct 9;2(8302):781-4
pubmed: 6126663
Lancet Glob Health. 2016 Aug;4(8):e534-47
pubmed: 27364568
Adv Virus Res. 1994;44:69-160
pubmed: 7817880
Nature. 2011 Nov 02;480(7378):530-3
pubmed: 22048310
Wkly Epidemiol Rec. 2012 Mar 2;87(9):73-81
pubmed: 22462199
J Infect Dis. 2018 Jun 5;218(1):124-132
pubmed: 29701813
JAMA. 1985 Mar 15;253(11):1574-7
pubmed: 3974036
J Neurosci Res. 2001 Sep 1;65(5):446-54
pubmed: 11536329
J Virol. 2011 Nov;85(21):11038-47
pubmed: 21880773
Epidemiol Infect. 2000 Dec;125(3):635-50
pubmed: 11218214
Epidemiol Infect. 2000 Dec;125(3):617-34
pubmed: 11218213
Lancet Glob Health. 2021 Mar;9(3):e280-e290
pubmed: 33607028
Viruses. 2016 Apr 21;8(4):112
pubmed: 27110811
Arch Virol. 1985;83(1-2):33-42
pubmed: 2578781
Nature. 2000 Aug 24;406(6798):893-7
pubmed: 10972291
Bull World Health Organ. 1997;75(1):55-68
pubmed: 9141751
Immunol Rev. 2010 Jul;236:176-89
pubmed: 20636817
Biomaterials. 2017 Jun;128:1-7
pubmed: 28285193
Lancet. 2017 Aug 12;390(10095):649-658
pubmed: 28666680
Clin Vaccine Immunol. 2012 Mar;19(3):396-400
pubmed: 22237896
J Clin Microbiol. 1992 Jul;30(7):1841-7
pubmed: 1629342
J Virol. 2012 Oct;86(20):11078-85
pubmed: 22855483
J Gen Virol. 1996 Feb;77 ( Pt 2 ):303-8
pubmed: 8627234
J Virol Methods. 2007 Dec;146(1-2):414-8
pubmed: 17919742
J Clin Microbiol. 1993 Jun;31(6):1521-4
pubmed: 8314994
J Infect Dis. 2004 Sep 1;190(5):998-1005
pubmed: 15295708
Int J Epidemiol. 2009 Feb;38(1):192-205
pubmed: 19188207
J Infect Dis. 2021 Sep 30;224(12 Suppl 2):S420-S428
pubmed: 34590128
J Clin Microbiol. 1985 Mar;21(3):449-51
pubmed: 3980696
Am J Epidemiol. 2000 Apr 1;151(7):723-35
pubmed: 10752800
MMWR Morb Mortal Wkly Rep. 2019 Oct 04;68(39):855-859
pubmed: 31581161
Epidemiol Infect. 2000 Jun;124(3):467-79
pubmed: 10982071
Lancet Glob Health. 2015 Sep;3(9):e528-36
pubmed: 26275329
Vaccine. 2018 Jan 11;36 Suppl 1:A35-A42
pubmed: 29307368
Ann Glob Health. 2020 Apr 06;86(1):35
pubmed: 32346521
Vaccine. 2013 Jul 25;31(34):3403-9
pubmed: 23044406
MMWR Morb Mortal Wkly Rep. 2015 Nov 13;64(44):1246-51
pubmed: 26562349
Vaccine. 2007 Dec 21;26(1):59-66
pubmed: 18063236
PLoS Med. 2005 Nov;2(11):e316
pubmed: 16218769
J Virol. 2013 Mar;87(6):3583-6
pubmed: 23283964
Lancet. 2015 Jun 6;385(9984):2297-307
pubmed: 25576992
Bull World Health Organ. 2017 Dec 01;95(12):831-841F
pubmed: 29200524
Western Pac Surveill Response J. 2012 Dec 20;3(4):33-8
pubmed: 23908937
Pediatr Infect Dis J. 1987 May;6(5):451-4
pubmed: 3601492
Science. 2019 Nov 1;366(6465):599-606
pubmed: 31672891
J Control Release. 2016 Oct 28;240:135-141
pubmed: 26603347
Vaccine. 2016 Sep 22;34(41):5034-5039
pubmed: 27570237
Viruses. 2016 Apr 21;8(4):109
pubmed: 27110809
Epidemiol Infect. 2012 Dec;140(12):2290-301
pubmed: 22335852
Vaccine. 2018 Jan 11;36 Suppl 1:A1-A34
pubmed: 29307367
J Clin Microbiol. 1996 Sep;34(9):2210-8
pubmed: 8862587
Cell Rep. 2015 Jun 9;11(9):1331-8
pubmed: 26004185
J Virol. 2003 Apr;77(7):4396-400
pubmed: 12634396
Lancet. 2017 Dec 2;390(10111):2490-2502
pubmed: 28673424
MMWR Morb Mortal Wkly Rep. 2021 Nov 12;70(45):1563-1569
pubmed: 34758014
Lancet Infect Dis. 2009 May;9(5):291-300
pubmed: 19393959