Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.
<h4>Background</h4>TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated.<h4>Methods and findings</h4>In this single-arm phase 2 trial, ad...
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Public Library of Science (PLoS)
2016-04-01
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| Online Access: | https://doi.org/10.1371/journal.pmed.1001997 |
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| author | Jake Dunning Foday Sahr Amanda Rojek Fiona Gannon Gail Carson Baimba Idriss Thomas Massaquoi Regina Gandi Sebatu Joseph Hassan K Osman Timothy J G Brooks Andrew J H Simpson Ian Goodfellow Lucy Thorne Armando Arias Laura Merson Lyndsey Castle Rebecca Howell-Jones Raul Pardinaz-Solis Benjamin Hope-Gill Mauricio Ferri Jennifer Grove Mark Kowalski Kasia Stepniewska Trudie Lang John Whitehead Piero Olliaro Mohammed Samai Peter W Horby RAPIDE-TKM trial team |
| author_facet | Jake Dunning Foday Sahr Amanda Rojek Fiona Gannon Gail Carson Baimba Idriss Thomas Massaquoi Regina Gandi Sebatu Joseph Hassan K Osman Timothy J G Brooks Andrew J H Simpson Ian Goodfellow Lucy Thorne Armando Arias Laura Merson Lyndsey Castle Rebecca Howell-Jones Raul Pardinaz-Solis Benjamin Hope-Gill Mauricio Ferri Jennifer Grove Mark Kowalski Kasia Stepniewska Trudie Lang John Whitehead Piero Olliaro Mohammed Samai Peter W Horby RAPIDE-TKM trial team |
| author_sort | Jake Dunning |
| collection | DOAJ |
| description | <h4>Background</h4>TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated.<h4>Methods and findings</h4>In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died.<h4>Conclusions</h4>Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls.<h4>Trial registration</h4>Pan African Clinical Trials Registry PACTR201501000997429. |
| format | Article |
| id | doaj-art-5d847f2d4b774f4e93d2e3fad6719689 |
| institution | Kabale University |
| issn | 1549-1277 1549-1676 |
| language | English |
| publishDate | 2016-04-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-5d847f2d4b774f4e93d2e3fad67196892025-08-20T03:25:15ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762016-04-01134e100199710.1371/journal.pmed.1001997Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.Jake DunningFoday SahrAmanda RojekFiona GannonGail CarsonBaimba IdrissThomas MassaquoiRegina GandiSebatu JosephHassan K OsmanTimothy J G BrooksAndrew J H SimpsonIan GoodfellowLucy ThorneArmando AriasLaura MersonLyndsey CastleRebecca Howell-JonesRaul Pardinaz-SolisBenjamin Hope-GillMauricio FerriJennifer GroveMark KowalskiKasia StepniewskaTrudie LangJohn WhiteheadPiero OlliaroMohammed SamaiPeter W HorbyRAPIDE-TKM trial team<h4>Background</h4>TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated.<h4>Methods and findings</h4>In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died.<h4>Conclusions</h4>Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls.<h4>Trial registration</h4>Pan African Clinical Trials Registry PACTR201501000997429.https://doi.org/10.1371/journal.pmed.1001997 |
| spellingShingle | Jake Dunning Foday Sahr Amanda Rojek Fiona Gannon Gail Carson Baimba Idriss Thomas Massaquoi Regina Gandi Sebatu Joseph Hassan K Osman Timothy J G Brooks Andrew J H Simpson Ian Goodfellow Lucy Thorne Armando Arias Laura Merson Lyndsey Castle Rebecca Howell-Jones Raul Pardinaz-Solis Benjamin Hope-Gill Mauricio Ferri Jennifer Grove Mark Kowalski Kasia Stepniewska Trudie Lang John Whitehead Piero Olliaro Mohammed Samai Peter W Horby RAPIDE-TKM trial team Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial. PLoS Medicine |
| title | Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial. |
| title_full | Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial. |
| title_fullStr | Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial. |
| title_full_unstemmed | Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial. |
| title_short | Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial. |
| title_sort | experimental treatment of ebola virus disease with tkm 130803 a single arm phase 2 clinical trial |
| url | https://doi.org/10.1371/journal.pmed.1001997 |
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