Ebola Virus InfectionPhase 1/2NCT02363322
Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection
A Phase 1/2 study of Ebola Virus Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 11 sites in 4 countries.
Trial summary
Background: Ebola is a viral infection that can spread quickly and causes life-threatening disease. Right now there is an Ebola outbreak in many countries in West Africa. There are no approved treatments for Ebola. But possible treatments are being developed. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Ebola Virus Infection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 13 Mar 2015to 31 Dec 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Males or females with documented positive PCR for Ebola virus infection within 10 days of enrollment
- Willingness of study participant to accept randomization to any assigned treatment arm
- Access to oSOC
- All males and females of childbearing potential, must be willing to use highly effective methods of contraception [e.g. absolute abstinence from potentially reproductive sexual activity, hormonal, surgical or multiple barrier/combined], from time of enrollment for the duration of study participation.
- Must agree not to enroll in another study of an investigational agent prior to completion of last required protocol visit (Day 58)
- Ability to provide informed consent personally, or by a legally-authorized [per applicable local laws and regulations] representative [LAR] if the patient is unable to do so.
Who cannot join
- Any medical condition that, in the opinion of the site investigator, would place the patient at an unreasonably increased risk through participation in this study, including any past or concurrent conditions that would preclude randomization to one or more of the assigned treatment arms.
- Prior treatment with any investigational antiviral drug therapy against Ebola infection other than experimental vaccines, within 5 half-lives or 30 days, whichever is longer, prior to enrollment
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
Sierra Leone7 sites
Police Training School 1 (PTS1), Western Rural District
Freetown
Emergency Ebola Treatment Unit
Goderich
Police Training School 2
Hastings
Chinese Friendship Hospital
Jui
International Medical Corps (IMC) Kambia
Kambia
International Medical Corps (IMC) Lunsar
Port Loko
Adventist Development and Relief Ebola Treatment Unit
Waterloo
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Multicenter Randomized Safety and Efficacy Study of Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection
Background:
- Ebola is a viral infection that can spread quickly and causes life-threatening disease. Right now there is an Ebola outbreak in many countries in West Africa. There are no approved treatments for Ebola. But possible treatments are being developed. Researchers need to study these treatments to see if they help people get better.
Read more
Objective:
- To identify possible Ebola treatments. Also, to learn if adding 1 or more experimental drugs to advanced Ebola care can reduce the risk of death.
Eligibility:
- People who have recently been diagnosed with Ebola, usually by a test called the Polymerase Chain Reaction (PCR), and have been hospitalized in an isolation unit for treatment.
Design:
- Participants will be randomly assigned to Group A or B. Both groups will get advanced level care. One group will also get an experimental drug.
- Participants may have blood tests. They may have another PCR test.
- Researchers will try to learn how the participant got Ebola.
- Participants put in the experimental drug group may start taking medicine within 24 hours of enrollment. It may be given by mouth or intravenously. Additional doses may be needed.
- Participants may have a series of timed blood tests over the first 24 to 48 hours after they take the medicine.
- Blood will be drawn frequently. Other body fluids (urine, stool, vaginal fluid, etc.) may also be collected.
- Participants will be followed for up to 60 days. They may be evaluated for any long-term effects of the experimental treatment(s). They may be asked to return for 1 or more outpatient visits.
- For consenting participants, follow-up will be extended for up to one full year past Day 58 with contact/visits every 1-3 months to assess for a history of signs or symptoms potentially consistent with late onset of virologic relapse syndrome.
Read the detailed description
Ebolaviruses (EBOV) are members of the Filoviridae and are known primarily as the underlying cause of severe viral hemorrhagic fevers with disturbingly high case fatality rates. Between 1994 and the present, there have been many EBOV outbreaks affecting mostly central Africa, with 2 large outbreaks in 1995 in Kikwit, Democratic Republic of Congo (DRC), and in Gulu, Uganda in 2000-2001. However, the 2014 West African outbreak significantly exceeds all previous outbreaks in geographic range, number of patients affected, and in disruption of typical activities of civil society.
There is strong consensus that the most important element necessary to improve survival from Ebola infection is the provision of full hemodynamic support in the form of aggressive fluid replacement, ability to diagnose and correct severe metabolic derangements, and other standards of modern medical care available in resource-rich environments. However, against this background, a small series of investigational agents or interventions have also been proposed as putative antiviral strategies of potential utility in treating this infection. Unfortunately, phase 1/2 data supporting the safety and efficacy of these agents is generally lacking, and thus there should be equipoise as to which, if any, of these interventions should be utilized in the treatment of severe infection.
In this multicenter randomized trial, we propose a flexible trial design with frequent interim monitoring to facilitate early elimination of poorly performing treatments as well as the introduction of new candidate therapies. The trial allows for a series of pairwise comparisons of novel interventions against a background of optimized medical care, with the goal of determining whether one or more of these interventions can improve the mortality over that achievable through optimized standard-of- care (oSOC) alone. The primary endpoint of this trial will be comparative mortality at Day 28, with a number of secondary endpoints that hopefully will generate generalizable knowledge about the relative safety and antiviral activity of these adjunctive interventions.
- Conditions
- Ebola Virus Infection
- Being tested
- B/Current Standard of Care Plus ZMapp, A/Current Standard of Care Alone
- Keywords
- Medical Countermeasures, VHF, EVD
- Medical subject headings
- Hemorrhagic Fever, Ebola
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
B/Current Standard of Care Plus ZMappDrug
Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
A/Current Standard of Care AloneOther
Optimized standard of care for Ebola virus infection
| Study group | Role | What they receive |
|---|---|---|
| A/Current Standard of Care Alone | Active comparator | A/Current Standard of Care Alone: Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting Receives: Other: A/Current Standard of Care Alone |
| B/Current Standard of Care Plus ZMapp | Experimental | B/Current Standard of Care Plus ZMapp: ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting.
ZMapp 50mg/kg IV administered every third day for 3 infusions. Receives: Drug: B/Current Standard of Care Plus ZMapp; Other: A/Current Standard of Care Alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality
Death at Day 28
Measured: 28 days
Secondary outcomes (2)
Number of Participants With ZMapp Infusion-related Adverse Events
Adverse events related to ZMapp infusions
Measured: 10 Days
Plasma Viral Load
Time to viral clearance
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2015 (estimated)
- Study start13 Mar 2015
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ebola Virus InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- The Ministry of Health and Social Welfare, Liberia, Ministry of Health and Sanitation, Sierra Leone, Institut National de la Santé Et de la Recherche Médicale, France, The Ministry of Health and Public Hygiene, Guinea
- Responsible party
- Sponsor
- Investigators
- Richard T Davey, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02363322
- Sponsor's protocol ID
- 150083
- Other IDs
- 15-I-0083
- Status last verified
- Jun 2018
- First submitted
- 13 Feb 2015
- Last updated
- 5 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Joffe S. Evaluating novel therapies during the Ebola epidemic. JAMA. 2014 Oct 1;312(13):1299-300. doi: 10.1001/jama.2014.12867. No abstract available.
PubMed 25211645Kanapathipillai R. Ebola virus disease--current knowledge. N Engl J Med. 2014 Sep 25;371(13):e18. doi: 10.1056/NEJMp1410741. No abstract available.
PubMed 25251632Piot P, Muyembe JJ, Edmunds WJ. Ebola in west Africa: from disease outbreak to humanitarian crisis. Lancet Infect Dis. 2014 Nov;14(11):1034-1035. doi: 10.1016/S1473-3099(14)70956-9. Epub 2014 Oct 1. No abstract available.
PubMed 25282665PREVAIL II Writing Group; Multi-National PREVAIL II Study Team; Davey RT Jr, Dodd L, Proschan MA, Neaton J, Neuhaus Nordwall J, Koopmeiners JS, Beigel J, Tierney J, Lane HC, Fauci AS, Massaquoi MBF, Sahr F, Malvy D. A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection. N Engl J Med. 2016 Oct 13;375(15):1448-1456. doi: 10.1056/NEJMoa1604330.
PubMed 27732819
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Safety and Efficacy Study of Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection
- ClinicalTrials.gov ID
- NCT02363322
- Acronym / sponsor ID
- 150083
- Conditions
- Ebola Virus Infection
- Keywords
- Medical Countermeasures, VHF, EVD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- The Ministry of Health and Social Welfare, Liberia, Ministry of Health and Sanitation, Sierra Leone, Institut National de la Santé Et de la Recherche Médicale, France, The Ministry of Health and Public Hygiene, Guinea
- Study start
- 13 Mar 2015 (actual)
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 16 Feb 2015 (estimated)
- Results
- Posted 14 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Ebola is a viral infection that can spread quickly and causes life-threatening disease. Right now there is an Ebola outbreak in many countries in West Africa. There are no approved treatments for Ebola. But possible treatments are being developed. Researchers need to study these treatments to see if they help people get better.
Objective:
- To identify possible Ebola treatments. Also, to learn if adding 1 or more experimental drugs to advanced Ebola care can reduce the risk of death.
Eligibility:
- People who have recently been diagnosed with Ebola, usually by a test called the Polymerase Chain Reaction (PCR), and have been hospitalized in an isolation unit for treatment.
Design:
- Participants will be randomly assigned to Group A or B. Both groups will get advanced level care. One group will also get an experimental drug.
- Participants may have blood tests. They may have another PCR test.
- Researchers will try to learn how the participant got Ebola.
- Participants put in the experimental drug group may start taking medicine within 24 hours of enrollment. It may be given by mouth or intravenously. Additional doses may be needed.
- Participants may have a series of timed blood tests over the first 24 to 48 hours after they take the medicine.
- Blood will be drawn frequently. Other body fluids (urine, stool, vaginal fluid, etc.) may also be collected.
- Participants will be followed for up to 60 days. They may be evaluated for any long-term effects of the experimental treatment(s). They may be asked to return for 1 or more outpatient visits.
- For consenting participants, follow-up will be extended for up to one full year past Day 58 with contact/visits every 1-3 months to assess for a history of signs or symptoms potentially consistent with late onset of virologic relapse syndrome.
Detailed description
Ebolaviruses (EBOV) are members of the Filoviridae and are known primarily as the underlying cause of severe viral hemorrhagic fevers with disturbingly high case fatality rates. Between 1994 and the present, there have been many EBOV outbreaks affecting mostly central Africa, with 2 large outbreaks in 1995 in Kikwit, Democratic Republic of Congo (DRC), and in Gulu, Uganda in 2000-2001. However, the 2014 West African outbreak significantly exceeds all previous outbreaks in geographic range, number of patients affected, and in disruption of typical activities of civil society.
There is strong consensus that the most important element necessary to improve survival from Ebola infection is the provision of full hemodynamic support in the form of aggressive fluid replacement, ability to diagnose and correct severe metabolic derangements, and other standards of modern medical care available in resource-rich environments. However, against this background, a small series of investigational agents or interventions have also been proposed as putative antiviral strategies of potential utility in treating this infection. Unfortunately, phase 1/2 data supporting the safety and efficacy of these agents is generally lacking, and thus there should be equipoise as to which, if any, of these interventions should be utilized in the treatment of severe infection.
In this multicenter randomized trial, we propose a flexible trial design with frequent interim monitoring to facilitate early elimination of poorly performing treatments as well as the introduction of new candidate therapies. The trial allows for a series of pairwise comparisons of novel interventions against a background of optimized medical care, with the goal of determining whether one or more of these interventions can improve the mortality over that achievable through optimized standard-of- care (oSOC) alone. The primary endpoint of this trial will be comparative mortality at Day 28, with a number of secondary endpoints that hopefully will generate generalizable knowledge about the relative safety and antiviral activity of these adjunctive interventions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A/Current Standard of Care Alone | Active comparator | Other: A/Current Standard of Care AloneA/Current Standard of Care Alone: Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting |
| B/Current Standard of Care Plus ZMapp | Experimental | Drug: B/Current Standard of Care Plus ZMapp, Other: A/Current Standard of Care AloneB/Current Standard of Care Plus ZMapp: ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMapp 50mg/kg IV administered every third day for 3 infusions. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Males or females with documented positive PCR for Ebola virus infection within 10 days of enrollment
- Willingness of study participant to accept randomization to any assigned treatment arm
- Access to oSOC
- All males and females of childbearing potential, must be willing to use highly effective methods of contraception [e.g. absolute abstinence from potentially reproductive sexual activity, hormonal, surgical or multiple barrier/combined], from time of enrollment for the duration of study participation.
- Must agree not to enroll in another study of an investigational agent prior to completion of last required protocol visit (Day 58)
Key exclusion criteria (2 listed)
- Any medical condition that, in the opinion of the site investigator, would place the patient at an unreasonably increased risk through participation in this study, including any past or concurrent conditions that would preclude randomization to one or more of the assigned treatment arms.
- Prior treatment with any investigational antiviral drug therapy against Ebola infection other than experimental vaccines, within 5 half-lives or 30 days, whichever is longer, prior to enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| B/Current Standard of Care Plus ZMappTriple monoclonal cocktail of antibodies against Zaire species of Ebola virus | Drug | B/Current Standard of Care Plus ZMapp |
| A/Current Standard of Care AloneOptimized standard of care for Ebola virus infection | Other | A/Current Standard of Care Alone, B/Current Standard of Care Plus ZMapp |
Primary outcome
Mortality
Time frame: 28 days
Death at Day 28
2 secondary outcomes
Number of Participants With ZMapp Infusion-related Adverse Events
Time frame: 10 Days
Plasma Viral Load
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25211645Joffe S. Evaluating novel therapies during the Ebola epidemic. JAMA. 2014 Oct 1;312(13):1299-300. doi: 10.1001/jama.2014.12867. No abstract available.
- Background: PubMed 25251632Kanapathipillai R. Ebola virus disease--current knowledge. N Engl J Med. 2014 Sep 25;371(13):e18. doi: 10.1056/NEJMp1410741. No abstract available.
- Background: PubMed 25282665Piot P, Muyembe JJ, Edmunds WJ. Ebola in west Africa: from disease outbreak to humanitarian crisis. Lancet Infect Dis. 2014 Nov;14(11):1034-1035. doi: 10.1016/S1473-3099(14)70956-9. Epub 2014 Oct 1. No abstract available.
- Derived from this study: PubMed 27732819PREVAIL II Writing Group; Multi-National PREVAIL II Study Team; Davey RT Jr, Dodd L, Proschan MA, Neaton J, Neuhaus Nordwall J, Koopmeiners JS, Beigel J, Tierney J, Lane HC, Fauci AS, Massaquoi MBF, Sahr F, Malvy D. A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection. N Engl J Med. 2016 Oct 13;375(15):1448-1456. doi: 10.1056/NEJMoa1604330.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard T Davey, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study of Ebola Virus Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 11 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Sierra Leone, Liberia, United States, Guinea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02363322, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2019.