A Phase 1/2 interventional study of B/Current Standard of Care Plus ZMapp and A/Current Standard of Care Alone in Ebola Virus Infection, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 11 sites in 4 countries. Per ClinicalTrials.gov, last updated 2019-06-05.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1/2, Interventional, and Treatment
Background:
Objective:
Eligibility:
Design:
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.
104 studies on the registry are indexed under Hemorrhagic Fever, Ebola; 13 are open to participants now.
This study's enrollment of 72 is below the median of 94 across 81 interventional studies indexed under Hemorrhagic Fever, Ebola.
Browse Hemorrhagic Fever, Ebola studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
EXCLUSION CRITERIA:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Other: A/Current Standard of Care Alone
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.
Drug: B/Current Standard of Care Plus ZMapp · Other: A/Current Standard of Care Alone
Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
Optimized standard of care for Ebola virus infection
Mortality
Death at Day 28
Time frame: 28 days
Number of Participants With ZMapp Infusion-related Adverse Events
Adverse events related to ZMapp infusions
Time frame: 10 Days
Plasma Viral Load
Time to viral clearance
Time frame: 28 days
Beginnning in March 2015 through November 2015 a total of 72 patients were enrolled at sites in Liberia, Sierra Leone, Guinea, and the United States.
| Milestone | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp |
|---|---|---|
| Started | 36 | 36 |
| Completed | 35 | 36 |
| Not completed | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
Death at Day 28
| Participants | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp |
|---|---|---|
| Mortality | 13 | 8 |
Adverse events related to ZMapp infusions
| participants | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp |
|---|---|---|
| Hypotension | — | 7 |
| Elevation in fever | — | 8 |
| Tachycardia | — | 4 |
| Tachypnea | — | 3 |
| Hypertension | — | 3 |
| Confusion | — | 2 |
| Seizure | — | 1 |
| Difficulty Breathing | — | 1 |
| Chills | — | 1 |
| Vomiting | — | 1 |
| Agitation | — | 1 |
Time to viral clearance
| days | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp |
|---|---|---|
| Plasma Viral Load | 13 (0 to 28) | 9 (0 to 28) |
Collected over 8 months, from March 2015 through November 2015. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| A/Current Standard of Care Alone | 13/35 (37.1%) | 13/35 (37.1%) | 0/35 (0%) |
| B/Current Standard of Care Plus ZMapp | 8/36 (22.2%) | 11/36 (30.6%) | 32/36 (88.9%) |
| Event | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp |
|---|---|---|
| Death due to EVDInfections and infestations | 10/35 | 2/36 |
| Multi-organ failure due to EVDInfections and infestations | 2/35 | 3/36 |
| Worsened renal insufficiencyRenal and urinary disorders | 1/35 | 0/36 |
| SyncopeNervous system disorders | 1/35 | 0/36 |
| Death due to Hypotensive ShockVascular disorders | 1/35 | 0/36 |
| Head InjuryNervous system disorders | 1/35 | 0/36 |
| Death due to sepsisInfections and infestations | 0/35 | 1/36 |
| Generalized seizureNervous system disorders | 0/35 | 1/36 |
| Hypovolemic shock due to acute hemorrhageVascular disorders | 0/35 | 1/36 |
| Severe diarrheaGastrointestinal disorders | 0/35 | 1/36 |
| Event | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp |
|---|---|---|
| Elevation in FeverInfections and infestations | — | 8/36 |
| HypotensionVascular disorders | — | 7/36 |
| TachycardiaVascular disorders | — | 4/36 |
| TachypneaRespiratory, thoracic and mediastinal disorders | — | 3/36 |
| HypertensionVascular disorders | — | 3/36 |
| ConfusionNervous system disorders | — | 2/36 |
| SeizureNervous system disorders | — | 1/36 |
| Difficulty BreathingRespiratory, thoracic and mediastinal disorders | — | 1/36 |
| ChillsInfections and infestations | — | 1/36 |
| VomitingGastrointestinal disorders | — | 1/36 |
| Age, Continuous(years) | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp | Total |
|---|---|---|---|
| Mean | 27.9 ± 16.4 | 24.3 ± 18.3 | 26.1 ± 17.4 |
| Sex: Female, Male(Participants) | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp | Total |
|---|---|---|---|
| Female | 17 | 23 | 40 |
| Male | 19 | 13 | 32 |
| Race (NIH/OMB)(Participants) | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 31 | 29 | 60 |
| White | 1 | 0 | 1 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 7 | 11 |
| Region of Enrollment(participants) | A/Current Standard of Care Alone | B/Current Standard of Care Plus ZMapp | Total |
|---|---|---|---|
| Liberia | 2 | 3 | 5 |
| United States | 1 | 0 | 1 |
| Guinea | 5 | 7 | 12 |
| Sierra Leone | 28 | 26 | 54 |
PDFs hosted by the registry, ClinicalTrials.gov.
This study is completed, as verified in Jun 2018. You cannot join it, but the record below documents what was studied.
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