Partnership for Research on Ebola Vaccines in Liberia (PREVAIL)

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ClinicalTrials.gov Identifier: NCT02344407

Recruitment Status : Active, not recruiting

First Posted : January 26, 2015

Results First Posted : August 1, 2017

Last Update Posted : April 15, 2020

Sponsor:

Information provided by (Responsible Party):

National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
Condition	Ebola Virus
Interventions	Biological: VSVG-ZEBOV Biological: ChAd3-EBO Z Biological: Placebo
Enrollment	1500

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	ChAd3-EBO Z	VSVG-ZEBOV	Placebo (Saline)
Arm/Group Description	ChAd3-EBO Z ...	VSVG-ZEBOV ...	Placebo
Arm/Group Description	ChAd3-EBO Z ChAd3-EBO Z: The ChAd3-EBO Z vaccine is comprised of a ChAd3 vector with a DNA fragment insert that encodes the Ebola virus glycoprotein, which is expressed on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion.	VSVG-ZEBOV VSVG-ZEBOV: The VSVdeltaG-ZEBOV vaccine is comprised of a single recombinant (vesicular stomatitis virus) VSV isolate (11481 nt) modified to replace the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Ebola virus Zaire strain (ZEBOV)	Placebo
Period Title: Overall Study
Started	500	500	500
Completed	492	491	494
Not Completed	8	9	6

Baseline Characteristics

Arm/Group Title		ChAd3-EBO Z	VSVG-ZEBOV	Placebo (Saline)	Total
Arm/Group Description		ChAd3-EBO Z ...	VSVG-ZEBOV ...	Placebo	Total of all reporting groups
Arm/Group Description		ChAd3-EBO Z ChAd3-EBO Z: The ChAd3-EBO Z vaccine is comprised of a ChAd3 vector with a DNA fragment insert that encodes the Ebola virus glycoprotein, which is expressed on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion.	VSVG-ZEBOV VSVG-ZEBOV: The VSVdeltaG-ZEBOV vaccine is comprised of a single recombinant (vesicular stomatitis virus) VSV isolate (11481 nt) modified to replace the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Ebola virus Zaire strain (ZEBOV)	Placebo	Total of all reporting groups
Overall Number of Baseline Participants		500	500	500	1500
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Inter-Quartile Range) Unit of measure: Years
	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
		30 (25 to 38)	29 (24 to 36)	30 (24 to 39)	30 (24 to 38)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
	Female	185 37.0%	187 37.4%	177 35.4%	549 36.6%
	Male	315 63.0%	313 62.6%	323 64.6%	951 63.4%
Region of Enrollment Measure Type: Number Unit of measure: Participants
Liberia	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
Liberia		500	500	500	1500
Contact past month with someone who had Ebola Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
		1 0.2%	5 1.0%	5 1.0%	11 0.7%
Work involves contact with persons with Ebola Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
		22 4.4%	25 5.0%	22 4.4%	69 4.6%
HIV Positive Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
		25 5.0%	22 4.4%	31 6.2%	78 5.2%
Syphilis positive Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
		30 6.0%	22 4.4%	25 5.0%	77 5.1%
IgG antibody level (EU/mL) Median (Inter-Quartile Range) Unit of measure: EU/mL
	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
		75 (44 to 135)	81 (49 to 141)	79 (50 to 148)	78 (47 to 139)
Positive antibody response Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	500 participants	500 participants	500 participants	1500 participants
		16 3.2%	18 3.6%	26 5.2%	60 4.0%

Outcome Measures

1.Primary Outcome


Title	Serious Adverse Events.
Description	Number of Participants Experiencing Serious Adverse Events in First 30...
Description	Number of Participants Experiencing Serious Adverse Events in First 30 Days
Time Frame	One month

Outcome Measure Data

Analysis Population Description

All Participants Randomized


Arm/Group Title	ChAd3-EBO Z	VSVG-ZEBOV	Placebo (Saline)
Arm/Group Description:	ChAd3-EBO Z ...	VSVG-ZEBOV ...	Placebo
Arm/Group Description:	ChAd3-EBO Z ChAd3-EBO Z: The ChAd3-EBO Z vaccine is comprised of a ChAd3 vector with a DNA fragment insert that encodes the Ebola virus glycoprotein, which is expressed on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion.	VSVG-ZEBOV VSVG-ZEBOV: The VSVdeltaG-ZEBOV vaccine is comprised of a single recombinant (vesicular stomatitis virus) VSV isolate (11481 nt) modified to replace the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Ebola virus Zaire strain (ZEBOV)	Placebo
Overall Number of Participants Analyzed	500	500	500
Measure Type: Count of Participants Unit of Measure: Participants
	6 1.2%	6 1.2%	8 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ChAd3-EBO Z, Placebo (Saline)
	Comments	Each active vaccine is compared to the placebo group
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.68
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	Bernards Exact Test Chi-square

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	VSVG-ZEBOV, Placebo (Saline)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.68
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	Barnard Exact Test Chi-square

2.Primary Outcome


Title	Immunogenicity Measures (ELISA and Neutralization Antigen-specific Assays for Antibody.
Description	Antibody Response at 1-Month (EU/mL) for Participants Without Elevated...
Description	Antibody Response at 1-Month (EU/mL) for Participants Without Elevated Levels at Entry
Time Frame	One month

Outcome Measure Data

Analysis Population Description

Participants with 1-month antibody data without elevated antibody levels at entry


Arm/Group Title	ChAd3-EBO Z	VSVG-ZEBOV	Placebo (Saline)
Arm/Group Description:	ChAd3-EBO Z ...	VSVG-ZEBOV ...	Placebo
Arm/Group Description:	ChAd3-EBO Z ChAd3-EBO Z: The ChAd3-EBO Z vaccine is comprised of a ChAd3 vector with a DNA fragment insert that encodes the Ebola virus glycoprotein, which is expressed on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion.	VSVG-ZEBOV VSVG-ZEBOV: The VSVdeltaG-ZEBOV vaccine is comprised of a single recombinant (vesicular stomatitis virus) VSV isolate (11481 nt) modified to replace the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Ebola virus Zaire strain (ZEBOV)	Placebo
Overall Number of Participants Analyzed	478	477	471
Geometric Mean (95% Confidence Interval) Unit of Measure: EU/mL
	621 (565 to 682)	1000 (910 to 1099)	75 (69 to 80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ChAd3-EBO Z, Placebo (Saline)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Linear regression (analysis of covariance) adjusted for baseline antibody level

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	VSVG-ZEBOV, Placebo (Saline)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline antibody level

Adverse Events

Time Frame	First 30 days after vaccination
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	ChAd3-EBO Z		VSVG-ZEBOV		Placebo (Saline)
Arm/Group Description	ChAd3-EBO Z ...		VSVG-ZEBOV ...		Placebo
Arm/Group Description	ChAd3-EBO Z ChAd3-EBO Z: The ChAd3-EBO Z vaccine is comprised of a ChAd3 vector with a DNA fragment insert that encodes the Ebola virus glycoprotein, which is expressed on the virion surface and is critical for attachment to host cells and catalysis of membrane fusion.		VSVG-ZEBOV VSVG-ZEBOV: The VSVdeltaG-ZEBOV vaccine is comprised of a single recombinant (vesicular stomatitis virus) VSV isolate (11481 nt) modified to replace the gene encoding the G envelope glycoprotein with the gene encoding the envelope glycoprotein from the Ebola virus Zaire strain (ZEBOV)		Placebo
All-Cause Mortality
	ChAd3-EBO Z		VSVG-ZEBOV		Placebo (Saline)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/500 (0.00%)		0/500 (0.00%)		1/500 (0.20%)
Serious Adverse Events Serious Adverse Events
	ChAd3-EBO Z		VSVG-ZEBOV		Placebo (Saline)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/500 (1.20%)		6/500 (1.20%)		8/500 (1.60%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/500 (0.20%)	1	0/500 (0.00%)	0	0/500 (0.00%)	0
Gastrointestinal disorders
Diarrhoea ^† 1	1/500 (0.20%)	1	0/500 (0.00%)	0	0/500 (0.00%)	0
Infections and infestations
Malaria ^† 1	2/500 (0.40%)	2	6/500 (1.20%)	6	6/500 (1.20%)	6
Typhoid fever ^† 1	1/500 (0.20%)	1	0/500 (0.00%)	0	0/500 (0.00%)	0
Pheumocystis jirovecii pheumonia ^† 1	0/500 (0.00%)	0	0/500 (0.00%)	0	1/500 (0.20%)	1
Injury, poisoning and procedural complications
Chest injury ^† 1	1/500 (0.20%)	1	0/500 (0.00%)	0	0/500 (0.00%)	0
Reproductive system and breast disorders
Vaginal haemorrhage ^† 1	0/500 (0.00%)	0	0/500 (0.00%)	0	1/500 (0.20%)	1
1 Term from vocabulary, MedDRA (10.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	ChAd3-EBO Z		VSVG-ZEBOV		Placebo (Saline)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/500 (0.00%)		0/500 (0.00%)		0/500 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Greg Grandits
Organization:	Division of Biostatistics, University of Minnesota
Phone:	612-626-9033
EMail:	grand001@umn.edu

Publications:

Feldmann H, Geisbert TW. Ebola haemorrhagic fever. Lancet. 2011 Mar 5;377(9768):849-62. doi: 10.1016/S0140-6736(10)60667-8. Review.

Chertow DS, Kleine C, Edwards JK, Scaini R, Giuliani R, Sprecher A. Ebola virus disease in West Africa--clinical manifestations and management. N Engl J Med. 2014 Nov 27;371(22):2054-7. doi: 10.1056/NEJMp1413084. Epub 2014 Nov 5.

Colloca S, Barnes E, Folgori A, Ammendola V, Capone S, Cirillo A, Siani L, Naddeo M, Grazioli F, Esposito ML, Ambrosio M, Sparacino A, Bartiromo M, Meola A, Smith K, Kurioka A, O'Hara GA, Ewer KJ, Anagnostou N, Bliss C, Hill AV, Traboni C, Klenerman P, Cortese R, Nicosia A. Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species. Sci Transl Med. 2012 Jan 4;4(115):115ra2. doi: 10.1126/scitranslmed.3002925.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Antonello J, Grant-Klein RJ, Nichols R, Kennedy SB, Dubey S, Simon JK. Serostatus cutoff levels and fold increase to define seroresponse to recombinant vesicular stomatitis virus - Zaire Ebola virus envelope glycoprotein vaccine: An evidence-based analysis. Vaccine. 2020 Jun 26;38(31):4885-4891. doi: 10.1016/j.vaccine.2020.04.061. Epub 2020 Jun 1.

Logue J, Tuznik K, Follmann D, Grandits G, Marchand J, Reilly C, Sarro YDS, Pettitt J, Stavale EJ, Fallah M, Olinger GG, Bolay FK, Hensley LE. Use of the Filovirus Animal Non-Clinical Group (FANG) Ebola virus immuno-assay requires fewer study participants to power a study than the Alpha Diagnostic International assay. J Virol Methods. 2018 May;255:84-90. doi: 10.1016/j.jviromet.2018.02.018. Epub 2018 Feb 23.

Kennedy SB, Bolay F, Kieh M, Grandits G, Badio M, Ballou R, Eckes R, Feinberg M, Follmann D, Grund B, Gupta S, Hensley L, Higgs E, Janosko K, Johnson M, Kateh F, Logue J, Marchand J, Monath T, Nason M, Nyenswah T, Roman F, Stavale E, Wolfson J, Neaton JD, Lane HC; PREVAIL I Study Group. Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia. N Engl J Med. 2017 Oct 12;377(15):1438-1447. doi: 10.1056/NEJMoa1614067.

Coller BG, Blue J, Das R, Dubey S, Finelli L, Gupta S, Helmond F, Grant-Klein RJ, Liu K, Simon J, Troth S, VanRheenen S, Waterbury J, Wivel A, Wolf J, Heppner DG, Kemp T, Nichols R, Monath TP. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic. Vaccine. 2017 Aug 16;35(35 Pt A):4465-4469. doi: 10.1016/j.vaccine.2017.05.097. Epub 2017 Jun 21.

Layout table for additonal information

Responsible Party:	National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
ClinicalTrials.gov Identifier:	NCT02344407
Other Study ID Numbers:	999915071 15-I-N071 ( Other Identifier: NIH IRB Protocol ID number )
First Submitted:	January 22, 2015
First Posted:	January 26, 2015
Results First Submitted:	May 25, 2017
Results First Posted:	August 1, 2017
Last Update Posted:	April 15, 2020

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