STRIVE (Sierra Leone Trial to Introduce a Vaccine Against Ebola) (STRIVE)

• ClinicalTrials.gov Identifier: NCT02378753
• Recruitment Status: Completed
• First Posted: March 4, 2015
• Results First Posted: April 5, 2018
• Last Update Posted: April 5, 2018
• Sponsor: Centers for Disease Control and Prevention
• Collaborators: University of Sierra Leone; Ministry of Health and Sanitation, Sierra Leone; Department of Health and Human Services; eHealth Africa
• Information provided by (Responsible Party): Centers for Disease Control and Prevention

Study Description

Brief Summary:

The 2014 outbreak of Ebola in West Africa is the largest in recorded history with widespread and intense transmission in Guinea, Liberia, and Sierra Leone. The high infectivity of blood and secretions, lack of appropriate personal protective equipment (PPE) and challenges in following infection control and prevention protocols put healthcare workers at high risk during outbreaks, and direct contact with the bodies of deceased Ebola victims can also sustain community transmission. This study will accelerate introduction and use of monovalent recombinant vesicular stomatitis virus Ebola vaccine (rVSVΔG-ZEBOV) among healthcare workers and frontline personnel involved in the Ebola outbreak response in Sierra Leone, while concurrently evaluating the safety and efficacy of the vaccine.

This is an unblinded, randomized trial with phased vaccine introduction in the target population. Participation in the study will be voluntary and open to adults 18 years of age and older who are at high risk of exposure to Ebola infection through their daily work and who work in a selected study area.

Condition or disease	Intervention/treatment	Phase
Hemorrhagic Fever, Ebola	Biological: rVSVΔG-ZEBOV	Phase 2; Phase 3

Detailed Description:

The Ebola outbreak was confirmed in March 2014 with widespread and intense transmission in Guinea, Liberia, and Sierra Leone. While there are no U.S. Food and Drug Administration (FDA)-approved pharmaceuticals to prevent or treat Ebola, two candidate vaccines are being tested in humans for dosing, tolerability, and safety. This study will evaluate monovalent recombinant vesicular stomatitis virus Ebola vaccine that remains replication competent (rVSVΔG-ZEBOV) in Sierra Leone.

The high infectivity of blood and secretions, lack of appropriate personal protective equipment (PPE) and challenges in following infection control and prevention protocols put healthcare workers at high risk during outbreaks, and direct contact with the bodies of deceased Ebola victims can also sustain community transmission.

This unblinded, randomized trial will evaluate vaccine efficacy (VE) and safety with phased vaccine introduction in the target population. Participation in the study will be voluntary and open to adults 18 years of age and older who are at high risk of exposure to Ebola infection through their daily work and who work in a selected study area. This includes: 1) personnel working in healthcare facilities where care is provided for Ebola patients; 2) personnel working in non-Ebola healthcare facilities who may have exposure to undiagnosed Ebola-infected individuals; and 3) personnel working in one of the following job categories: surveillance team, ambulance team, or laboratory worker responsible for swabbing deceased persons. Staff members involved in this study are also eligible to receive the vaccine under this protocol; study staff will be followed for 6 months post-vaccination to monitor for safety of rVSVΔG-ZEBOV.

Eligible participants within a healthcare facility or frontline team will be enrolled and individually randomized to either immediate or deferred vaccination. A single dose of rVSVΔG-ZEBOV will be administered intramuscularly. Immediate vaccination is defined as vaccination within 7 days of enrollment and deferred vaccination is defined as vaccination at the end of an 18-24 week follow-up period. Participants will not be blinded to the randomized assignment of immediate or deferred vaccination. All enrolled participants will have the opportunity to receive rVSVΔG-ZEBOV by the end of the study. Enrollment and vaccination will be phased over time.

Ebola events that occur during the 18-24 week post-enrollment will be included in the VE analysis, with the immediate vaccination arm contributing vaccinated follow-up time and the deferred vaccination arm contributing unvaccinated follow-up time. All participants, regardless of randomized assignment, will be followed for 6 months after vaccination to monitor for safety of rVSVΔG-ZEBOV.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8651 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: [rVSVΔG-ZEBOV] Ebola Prevention Vaccine Evaluation in Sierra Leone
• Study Start Date: April 2015
• Actual Primary Completion Date: November 8, 2016
• Actual Study Completion Date: December 5, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: rVSVΔG-ZEBOV (immediate vaccination); One intramuscular (deltoid) injection of rVSVΔG-ZEBOV (2 x 10^7 plaque forming units)	Biological: rVSVΔG-ZEBOV; The rVSVΔG-ZEBOV vaccine is comprised of a single recombinant VSV isolate (11481 nontypeable) modified to replace the gene encoding the G envelope GP with the gene encoding the envelope GP from ZEBOV (Kikwit, 1995 strain).; Other Name: BPSC-1001
Experimental: rVSVΔG-ZEBOV (deferred vaccination); One intramuscular (deltoid) injection of rVSVΔG-ZEBOV (2 x 10^7 plaque forming units) in participants randomized to receive deferred vaccination (18-24 weeks after enrollment).	Biological: rVSVΔG-ZEBOV; The rVSVΔG-ZEBOV vaccine is comprised of a single recombinant VSV isolate (11481 nontypeable) modified to replace the gene encoding the G envelope GP with the gene encoding the envelope GP from ZEBOV (Kikwit, 1995 strain).; Other Name: BPSC-1001

Outcome Measures

Primary Outcome Measures :

1. Laboratory-confirmed Ebola (Study Diagnostics) [ Time Frame: > 21 days following vaccination ]

   Incidence of Ebola confirmed by the STRIVE study laboratory in each treatment group during the Randomized Portion of the trial. For the vaccine efficacy endpoint, all enrolled participants in both arms were followed for 18-24 weeks after enrollment (after which point participants in the deferred cohort received crossover vaccination). Statistical analysis was to proceed as survival analysis (time-to-event/time-to-infection) of cohort follow-up data during this period.

   There were no laboratory-confirmed cases of Ebola among study participants, so therefore no efficacy analyses were performed.

2. Number of Participants With Occurrence of Serious Adverse Events During the 6 Months Following the Vaccination [ Time Frame: 6 months following vaccination ]
   Number of Participants with Occurrence of SAEs within the 6-month follow-up period following a single dose of rVSVΔG-ZEBOV. Vaccination in the immediate group occurred within 7 days of enrollment if possible, and vaccination in the deferred-vaccination group occurred 18-24 weeks after enrollment.

Secondary Outcome Measures :

1. Death Due to Laboratory-confirmed Ebola [ Time Frame: 6 months following vaccination ]
   Deaths due to Ebola confirmed by the STRIVE study laboratory in each treatment group during the Randomized Portion of the trial. There were no laboratory-confirmed cases of Ebola among study participants, so therefore no efficacy analyses were performed.
2. Ebola Confirmed by Non-study or Study Diagnostics [ Time Frame: 6 months following vaccination ]
   Incidence of Ebola confirmed by the STRIVE study laboratory or by a non-study laboratory in each treatment group during the Randomized Portion of the trial. For the vaccine efficacy endpoint, all enrolled participants in both arms were followed for 18-24 weeks after enrollment (after which point participants in the deferred cohort received crossover vaccination). Statistical analysis was to proceed as survival analysis (time-to-event/time-to-infection) of cohort follow-up data during this period. There were no laboratory-confirmed cases of Ebola among study participants, so therefore no efficacy analyses were performed.
3. Suspected, Probable or Laboratory-confirmed Ebola [ Time Frame: 6 months following vaccination ]
   Incidence of suspected, probable, or laboratory-confirmed Ebola, where "suspected" and "probable" cases are defined by the August 9, 2014 World Health Organization case definition recommendations for use during an Ebola outbreak, and laboratory-confirmed Ebola includes both study laboratory and non-study laboratory diagnostics. An Ebola Screening Form was required to be completed for all participants referred for evaluation of suspected Ebola; the Outcome Measure (Count of Participants) reflects the number of participants in each group for whom an Ebola Screening Form was completed.
4. Number of Participants With Occurrence of Solicited Injection-site and Systemic Reactogenicity Signs and Symptoms, Including Fever, on Vaccination Day and During the 7 Days Following the Vaccination or Enrollment. [ Time Frame: Vaccination day and for 7 days following vaccination ]
   Solicited symptoms were assessed only in safety sub-study participants (the first 449 participants enrolled at the COMAHS Library site), during the 7 days after vaccination (immediate group) or after enrollment without vaccination (deferred group). Participants were actively solicited for the occurrence of local (injection-site) pain, redness, and swelling and the following systemic reactogenicity symptoms: fever, joint pain, joint swelling, muscle pain, fatigue, feeling unwell, chills, headache, vomiting, nausea, diarrhea, abdominal pain, rash, oral ulcers, and skin vesicles (blisters).
5. Number of Participants With Occurrence of Solicited and Unsolicited AEs During the 28 Days Following the Vaccination or Enrollment [ Time Frame: During 28 days following vaccination ]
   Solicited local and systemic reactogenicity symptoms and unsolicited adverse events were assessed in safety sub-study participants (the first 449 participants enrolled at the COMAHS Library site), during the 28 days after vaccination (immediate group) or after enrollment without vaccination (deferred group).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Age 18 years or older.

2. Member of target population at the time of enrollment:

   • active worker in an Ebola care, holding, or treatment center (may include physicians, nurses, nurse aides, lab technicians, pharmacists, pharmacy technicians, cleaners, and security and administrative staff);
   • active worker in a facility providing non-Ebola-related healthcare (may include physicians, nurses, nurse aides, lab technicians, pharmacists, pharmacy technicians, cleaners, and security and administrative staff);
   • active frontline worker in one of the following job categories: surveillance team, ambulance team, burial worker, or worker responsible for swabbing deceased persons.
3. Reasonably anticipates living in Sierra Leone for the 18-24 weeks following enrollment.
4. Reachable by phone throughout the 6 month post-vaccination safety follow-up period.
5. Willing to adhere to personal protective equipment (PPE) and infection control recommendations.
6. Able and willing to complete the informed consent process and study procedures.
7. Willing to receive vaccine in either the immediate or the deferred trial arms, according to random assignment.

Exclusion Criteria:

1. History of Ebola (self-report).
2. Prior receipt of experimental Ebola or Marburg vaccine.
3. History of human immunodeficiency virus (HIV) or clinically important immunodeficiency (self-report).
4. Any history of allergy or anaphylaxis to prior vaccines
5. Breast-feeding an infant or child.
6. Any reason the investigator suspects that data collected from this person would be incomplete or of poor quality.
7. Current pregnancy (a negative urine pregnancy test is required for women participants <50 years of age who self-report as not pregnant).
8. Currently being followed for known exposure to Ebola.
9. Known experimental research agents or other vaccine within 28 days (4 weeks) before vaccination.
10. Fever ≥ 38.0°C (100.4°F) at time of vaccination.

Contacts and Locations

Locations

Sierra Leone

College of Medicine and Allied Health Sciences (COMAHS)

Freetown, Western Area Urban, Sierra Leone

Bombali

Bombali District, Sierra Leone

Port Loko

Port Loko District, Sierra Leone

Tonkolili

Tonkolili District, Sierra Leone

Western Area Rural

Western Area District, Sierra Leone

Sponsors and Collaborators

Centers for Disease Control and Prevention

University of Sierra Leone

Ministry of Health and Sanitation, Sierra Leone

Department of Health and Human Services

eHealth Africa

Investigators

• Principal Investigator: Mohamed Samai, MBChB,PhD; University of Sierra Leone

More Information

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

Simon JK, Kennedy SB, Mahon BE, Dubey SA, Grant-Klein RJ, Liu K, Hartzel J, Coller BG, Welebob C, Hanson ME, Grais RF. Immunogenicity of rVSVDeltaG-ZEBOV-GP Ebola vaccine (ERVEBO(R)) in African clinical trial participants by age, sex, and baseline GP-ELISA titer: A post hoc analysis of three Phase 2/3 trials. Vaccine. 2022 Nov 2;40(46):6599-6606. doi: 10.1016/j.vaccine.2022.09.037. Epub 2022 Oct 5.

Legardy-Williams JK, Carter RJ, Goldstein ST, Jarrett OD, Szefer E, Fombah AE, Tinker SC, Samai M, Mahon BE. Pregnancy Outcomes among Women Receiving rVSVDelta-ZEBOV-GP Ebola Vaccine during the Sierra Leone Trial to Introduce a Vaccine against Ebola. Emerg Infect Dis. 2020 Mar;26(3):541-548. doi: 10.3201/eid2603.191018. Epub 2020 Mar 17.

Kabineh AK, Carr W, Motevalli M, Legardy-Williams J, Vincent W, Mahon BE, Samai M. Operationalizing International Regulatory Standards in a Limited-Resource Setting During an Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE) Experience. J Infect Dis. 2018 May 18;217(suppl_1):S56-S59. doi: 10.1093/infdis/jiy111.

Carter RJ, Senesi RGB, Dawson P, Gassama I, Kargbo SAS, Petrie CR, Rogers MH, Samai M, Luman ET. Participant Retention in a Randomized Clinical Trial in an Outbreak Setting: Lessons From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE). J Infect Dis. 2018 May 18;217(suppl_1):S65-S74. doi: 10.1093/infdis/jiy094.

Conteh MA, Goldstein ST, Wurie HR, Gidudu J, Lisk DR, Carter RJ, Seward JF, Hampton LM, Wang D, Andersen LE, Arvay M, Schrag SJ, Dawson P, Fombah AE, Petrie CR, Feikin DR, Russell JBW, Lindblad R, Kargbo SAS, Samai M, Mahon BE. Clinical Surveillance and Evaluation of Suspected Ebola Cases in a Vaccine Trial During an Ebola Epidemic: The Sierra Leone Trial to Introduce a Vaccine Against Ebola. J Infect Dis. 2018 May 18;217(suppl_1):S33-S39. doi: 10.1093/infdis/jiy061.

Jarrett OD, Seward JF, Fombah AE, Lindblad R, Jalloh MI, El-Khorazaty J, Dawson P, Burton D, Zucker J, Carr W, Bah MM, Deen GF, George PM, James F, Lisk DR, Pratt D, Russell JBW, Sandy JD, Turay P, Hamel MJ, Schrag SJ, Walker RE, Samai M, Goldstein ST. Monitoring Serious Adverse Events in the Sierra Leone Trial to Introduce a Vaccine Against Ebola. J Infect Dis. 2018 May 18;217(suppl_1):S24-S32. doi: 10.1093/infdis/jiy042.

Samai M, Seward JF, Goldstein ST, Mahon BE, Lisk DR, Widdowson MA, Jalloh MI, Schrag SJ, Idriss A, Carter RJ, Dawson P, Kargbo SAS, Leigh B, Bawoh M, Legardy-Williams J, Deen G, Carr W, Callis A, Lindblad R, Russell JBW, Petrie CR, Fombah AE, Kargbo B, McDonald W, Jarrett OD, Walker RE, Gargiullo P, Bash-Taqi D, Gibson L, Fofanah AB, Schuchat A; STRIVE Study Team. The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An Evaluation of rVSV∆G-ZEBOV-GP Vaccine Tolerability and Safety During the West Africa Ebola Outbreak. J Infect Dis. 2018 May 18;217(suppl_1):S6-S15. doi: 10.1093/infdis/jiy020. Erratum In: J Infect Dis. 2018 Jul 2;218(3):508-507.

Carter RJ, Idriss A, Widdowson MA, Samai M, Schrag SJ, Legardy-Williams JK, Estivariz CF, Callis A, Carr W, Webber W, Fischer ME, Hadler S, Sahr F, Thompson M, Greby SM, Edem-Hotah J, Momoh RM, McDonald W, Gee JM, Kallon AF, Spencer-Walters D, Bresee JS, Cohn A, Hersey S, Gibson L, Schuchat A, Seward JF. Implementing a Multisite Clinical Trial in the Midst of an Ebola Outbreak: Lessons Learned From the Sierra Leone Trial to Introduce a Vaccine Against Ebola. J Infect Dis. 2018 May 18;217(suppl_1):S16-S23. doi: 10.1093/infdis/jix657.

Fombah AE, Goldstein ST, Jarrett OD, Jalloh MI, El-Khorazaty J, Lisk DR, Legardy-Williams J, Pratt DA, George PM, Russell JBW, Schrag SJ, Dawson P, Deen GF, Carr W, Lindblad R, James F, Bah MM, Yillia JF, Sandy JD, Turay PE, Conteh MA, Slutsker L, Mahon BE, Samai M, Seward JF. Health Conditions in an Adult Population in Sierra Leone: Data Reported From the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE). J Infect Dis. 2018 May 18;217(suppl_1):S75-S80. doi: 10.1093/infdis/jix603.

Callis A, Carter VM, Ramakrishnan A, Albert AP, Conteh L, Barrie AA, Fahnbulleh L, Koroma MM, Saidu S, Williams O, Samai M. Lessons Learned in Clinical Trial Communication During an Ebola Outbreak: The Implementation of STRIVE. J Infect Dis. 2018 May 18;217(suppl_1):S40-S47. doi: 10.1093/infdis/jix558.

Edem-Hotah J, McDonald W, Abu PM, Luman ET, Carter RJ, Koker A, Goldstein ST. Utilizing Nurses to Staff an Ebola Vaccine Clinical Trial in Sierra Leone during the Ebola Outbreak. J Infect Dis. 2018 May 18;217(suppl_1):S60-S64. doi: 10.1093/infdis/jix389.

Jusu MO, Glauser G, Seward JF, Bawoh M, Tempel J, Friend M, Littlefield D, Lahai M, Jalloh HM, Sesay AB, Caulker AF, Samai M, Thomas V, Farrell N, Widdowson MA. Rapid Establishment of a Cold Chain Capacity of -60 degrees C or Colder for the STRIVE Ebola Vaccine Trial During the Ebola Outbreak in Sierra Leone. J Infect Dis. 2018 May 18;217(suppl_1):S48-S55. doi: 10.1093/infdis/jix336.

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.

• Responsible Party: Centers for Disease Control and Prevention
• ClinicalTrials.gov Identifier: NCT02378753
• Other Study ID Numbers: CDC-NCIRD-6689
• First Posted: March 4, 2015
• Results First Posted: April 5, 2018
• Last Update Posted: April 5, 2018
• Last Verified: July 2016

• Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Centers for Disease Control and Prevention:

Ebola; Sierra Leone; vaccine; rVSVΔG-ZEBOV

Additional relevant MeSH terms:

Hemorrhagic Fever, Ebola; Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections