NCT02363322

Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection

Completed Phase 1, PHASE2 Results posted Last updated 5 June 2019

What this trial tests

Phase 1, PHASE2 trial testing B/Current Standard of Care Plus ZMapp in Ebola Virus Infection in 72 participants. Completed in 31 December 2017.

Timeline

13 March 2015

Primary endpoint
31 December 2017

31 December 2017

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	72
Start date	13 March 2015
Primary completion	31 December 2017
Estimated completion	31 December 2017
Sites	11 locations across Liberia, United States, Sierra Leone, Guinea

Drugs / interventions tested

• B/Current Standard of Care Plus ZMapp — full drug profile →
• A/Current Standard of Care Alone

Conditions studied

• Ebola Virus Infection — all drugs for Ebola Virus Infection →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Eligibility, any sex, with Ebola Virus Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mortality Primary · 28 days

Death at Day 28

Group	Value	95% CI
A/Current Standard of Care Alone	13
B/Current Standard of Care Plus ZMapp	8

Number of Participants With ZMapp Infusion-related Adverse Events Secondary · 10 Days

Adverse events related to ZMapp infusions

Hypotension

Group	Value	95% CI
B/Current Standard of Care Plus ZMapp	7

Elevation in fever

Group	Value	95% CI
B/Current Standard of Care Plus ZMapp	8

Tachycardia

Group	Value	95% CI
B/Current Standard of Care Plus ZMapp	4

Tachypnea

Group	Value	95% CI
B/Current Standard of Care Plus ZMapp	3

Hypertension

Group	Value	95% CI
B/Current Standard of Care Plus ZMapp	3

Confusion

Group	Value	95% CI
B/Current Standard of Care Plus ZMapp	2

Seizure

Group	Value	95% CI
B/Current Standard of Care Plus ZMapp	1

Difficulty Breathing

Group	Value	95% CI
B/Current Standard of Care Plus ZMapp	1

Plasma Viral Load Secondary · 28 days

Time to viral clearance

Group	Value	95% CI
A/Current Standard of Care Alone	13	0 – 28
B/Current Standard of Care Plus ZMapp	9	0 – 28

Adverse events — posted to ClinicalTrials.gov

Time frame: 8 months, from March 2015 through November 2015. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

A/Current Standard of Care Alone

Serious: 13/35 (37%)

Deaths: 13/35

B/Current Standard of Care Plus ZMapp

Serious: 11/36 (31%)

Deaths: 8/36

Serious adverse events (12 terms)

Reaction	System	A/Current Standard of Care…	B/Current Standard of Care…
Death due to EVD	Infections and infestations	—	—
Multi-organ failure due to EVD	Infections and infestations	—	—
Worsened renal insufficiency	Renal and urinary disorders	—	—
Syncope	Nervous system disorders	—	—
Death due to Hypotensive Shock	Vascular disorders	—	—
Head Injury	Nervous system disorders	—	—
Death due to sepsis	Infections and infestations	—	—
Generalized seizure	Nervous system disorders	—	—
Hypovolemic shock due to acute hemorrhage	Vascular disorders	—	—
Severe diarrhea	Gastrointestinal disorders	—	—
Arterial Hypertension	Vascular disorders	—	—
Hospitalization with febrile illness (malaria)	Infections and infestations	—	—

Other adverse events (11 terms — click to expand)

Reaction	System	A/Current Standard of Care…	B/Current Standard of Care…
Elevation in Fever	Infections and infestations	—	—
Hypotension	Vascular disorders	—	—
Tachycardia	Vascular disorders	—	—
Tachypnea	Respiratory, thoracic and mediastinal disorders	—	—
Hypertension	Vascular disorders	—	—
Confusion	Nervous system disorders	—	—
Seizure	Nervous system disorders	—	—
Difficulty Breathing	Respiratory, thoracic and mediastinal disorders	—	—
Chills	Infections and infestations	—	—
Vomiting	Gastrointestinal disorders	—	—
Agitation	Nervous system disorders	—	—

Most-reported serious reactions: Death due to EVD, Multi-organ failure due to EVD, Worsened renal insufficiency, Syncope, Death due to Hypotensive Shock, Head Injury, Death due to sepsis, Generalized seizure.

Data from ClinicalTrials.gov NCT02363322 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Ebola virus disease.
   Jacob ST, Crozier I, Fischer WA, Hewlett A, et al · · 2020 · cited 428× · PMID 32080199 · DOI 10.1038/s41572-020-0147-3
2. A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection.
   PREVAIL II Writing Group, Multi-National PREVAIL II Study Team, Davey RT, Dodd L, et al · · 2016 · cited 378× · PMID 27732819 · DOI 10.1056/nejmoa1604330
3. Antibody therapies for the prevention and treatment of viral infections.
   Salazar G, Zhang N, Fu TM, An Z. · · 2017 · cited 135× · PMID 29263875 · DOI 10.1038/s41541-017-0019-3
4. Plants as Factories for Human Pharmaceuticals: Applications and Challenges.
   Yao J, Weng Y, Dickey A, Wang KY. · · 2015 · cited 134× · PMID 26633378 · DOI 10.3390/ijms161226122
5. Drug combination therapy for emerging viral diseases.
   Shyr ZA, Cheng YS, Lo DC, Zheng W. · · 2021 · cited 125× · PMID 34023496 · DOI 10.1016/j.drudis.2021.05.008
6. Protected to death: systematic exclusion of pregnant women from Ebola virus disease trials.
   Gomes MF, de la Fuente-Núñez V, Saxena A, Kuesel AC. · · 2017 · cited 65× · PMID 29297366 · DOI 10.1186/s12978-017-0430-2
7. Insights from clinical research completed during the west Africa Ebola virus disease epidemic.
   Rojek A, Horby P, Dunning J. · · 2017 · cited 56× · PMID 28461209 · DOI 10.1016/s1473-3099(17)30234-7
8. A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus.
   McCarthy SD, Majchrzak-Kita B, Racine T, Kozlowski HN, et al · · 2016 · cited 47× · PMID 26752302 · DOI 10.1371/journal.pntd.0004364