Safety Evaluation of Topical Application of Nano-Liposomal Form of Amphotericin B (SinaAmpholeish) on Healthy Volunteers; Phase I Clinical Trial

Background: We aimed to evaluate the safety of SinaAmpholeish in a double-blind, randomized, phase 1 clinical trial in healthy human volunteers. Methods: The study was carried out in DermaLab of Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran in 2012. A topical Nano-liposomal formulation of 0.4% Amphotericin B was developed against Leishmania under trade name of SinaAmpholeish. In this randomized, double-blind, right-left, comparative, phase I clinical trial, in 2 steps; 7 and 20 healthy volunteers were recruited and applied SinaAmpholeish on the right and its vehicle on the left volar side of forearm, twice a day for one week or 3 times a day for two weeks. Seven biophysical skin parameters were measured in standard conditions before and 2 wk after application. Results: There was no adverse effect when SinaAmpholeish and its vehicle were used twice a day for seven days. However, when were used 3 times a day for two weeks, both SinaAmpholeish and its vehicle induced severe local skin reactions in 2 volunteers leading to discontinuation of application. Mild and temporary local reactions were observed in about half of the application sides and there was no significant difference between SinaAmpholeish and its vehicle. Conclusion: The new formulation is safe and worth to be tested in further phase 2 clinical trial and since there was no adverse effect with twice a day application it was decided to use SinaAmpholeish twice a day in phase 2 clinical trial.

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Correction to: Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

Trials ◽

10.1186/s13063-021-05572-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Moses Badio ◽

Edouard Lhomme ◽

Mark Kieh ◽

Abdoul Habib Beavogui ◽

Stephen B. Kennedy ◽

...

Keyword(s):

Clinical Trial ◽

Healthy Volunteers ◽

West African ◽

Phase 2 ◽

African Countries ◽

Double Blind ◽

Double Blind Placebo ◽

Phase 2 Clinical Trial

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Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

10.21203/rs.3.rs-30774/v1 ◽

2020 ◽

Author(s):

Moses Badio ◽

Edouard Lhomme ◽

Mark Kieh ◽

Abdoul Habib Beavogui ◽

Stephen B Kennedy ◽

...

Keyword(s):

Clinical Trial ◽

Healthy Volunteers ◽

Antibody Titer ◽

Ebola Virus ◽

Surface Glycoprotein ◽

Phase 2 ◽

Double Blind ◽

Virus Surface ◽

Double Blind Placebo ◽

Phase 2 Clinical Trial

Abstract IntroductionThe Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments.MethodsThis is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection.ResultsFrom April 2017 to December 2018, a total of 5,002 volunteers were screened and 4,789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4,789 participants, 2,560 (53%) were adults and 2,229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years; 750 (16%) 5 to 11 years; and 930 (19%) aged 12–17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1,090 participants was 72 (50, 116) EU/mL.DiscussionThe PREVAC trial is evaluating - placebo-controlled - two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children.Trial registrationClinicaltrials.gov, NCT02876328. Registred 23 August 2016, https://clinicaltrials.gov/ct2/show/NCT02876328

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Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

Trials ◽

10.1186/s13063-021-05035-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Moses Badio ◽

◽

Edouard Lhomme ◽

Mark Kieh ◽

Abdoul Habib Beavogui ◽

...

Keyword(s):

Clinical Trial ◽

Healthy Volunteers ◽

Antibody Titer ◽

Ebola Virus ◽

Surface Glycoprotein ◽

Phase 2 ◽

Double Blind ◽

Virus Surface ◽

Double Blind Placebo ◽

Phase 2 Clinical Trial

Abstract Introduction The Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments. Methods This is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection. Results From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12–17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL. Discussion The PREVAC trial is evaluating—placebo-controlled—two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children. Trial registration ClinicalTrials.gov NCT02876328. Registered on 23 August 2016.

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