Trial Outcomes & Findings for Putative Investigational Therapeutics in the Treatment of Patients With Known Ebola Infection (NCT NCT02363322)

NCT ID: NCT02363322

Last Updated: 2019-06-05

Results Overview

Death at Day 28

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 72 participants
• Primary outcome timeframe: 28 days
• Results posted on: 2019-06-05

Participant Flow

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.

Participant milestones

Measure	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 Treatment A: Optimized standard of care for Ebola virus infection	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: Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
Overall Study STARTED	36	36
Overall Study COMPLETED	35	36
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	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 Treatment A: Optimized standard of care for Ebola virus infection	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: Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	A/Current Standard of Care Alone n=36 Participants 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 n=36 Participants ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMApp: Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus	Total n=72 Participants Total of all reporting groups
Age, Continuous	27.9 years STANDARD_DEVIATION 16.4 • n=5 Participants	24.3 years STANDARD_DEVIATION 18.3 • n=7 Participants	26.1 years STANDARD_DEVIATION 17.4 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	23 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	13 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	31 Participants n=5 Participants	29 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Liberia	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Guinea	5 participants n=5 Participants	7 participants n=7 Participants	12 participants n=5 Participants
Region of Enrollment Sierra Leone	28 participants n=5 Participants	26 participants n=7 Participants	54 participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days

Population: Seven of the eight deaths recorded in ZMapp recipients occurred before day 4, before the second of three planned infusions of ZMapp. The exception was one patient who received a second infusion on day 4 and died later that day. In the group that received the current standard of care alone, all 13 deaths occurred during the first 8 days of follow-up

Death at Day 28

Outcome measures

Measure	A/Current Standard of Care Alone n=35 Participants 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 n=36 Participants ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMApp: Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
Mortality	13 Participants	8 Participants

SECONDARY outcome

Timeframe: 10 Days

Population: Arm A Received the Current Standard of Care Alone and not the ZMapp infusion

Adverse events related to ZMapp infusions

Outcome measures

Measure	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	B/Current Standard of Care Plus ZMapp n=36 Participants ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMApp: Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
Number of Participants With ZMapp Infusion-related Adverse Events Hypotension	—	7 participants
Number of Participants With ZMapp Infusion-related Adverse Events Elevation in fever	—	8 participants
Number of Participants With ZMapp Infusion-related Adverse Events Tachycardia	—	4 participants
Number of Participants With ZMapp Infusion-related Adverse Events Tachypnea	—	3 participants
Number of Participants With ZMapp Infusion-related Adverse Events Hypertension	—	3 participants
Number of Participants With ZMapp Infusion-related Adverse Events Confusion	—	2 participants
Number of Participants With ZMapp Infusion-related Adverse Events Seizure	—	1 participants
Number of Participants With ZMapp Infusion-related Adverse Events Difficulty Breathing	—	1 participants
Number of Participants With ZMapp Infusion-related Adverse Events Chills	—	1 participants
Number of Participants With ZMapp Infusion-related Adverse Events Vomiting	—	1 participants
Number of Participants With ZMapp Infusion-related Adverse Events Agitation	—	1 participants

SECONDARY outcome

Timeframe: 28 days

Time to viral clearance

Outcome measures

Measure	A/Current Standard of Care Alone n=35 Participants 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 n=36 Participants ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMApp: Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
Plasma Viral Load	13 days Interval 0.0 to 28.0	9 days Interval 0.0 to 28.0

Adverse Events

A/Current Standard of Care Alone

Serious events: 13 serious events

Other events: 0 other events

Deaths: 13 deaths

B/Current Standard of Care Plus ZMapp

Serious events: 11 serious events

Other events: 32 other events

Deaths: 8 deaths

Serious adverse events

Measure	A/Current Standard of Care Alone n=35 participants at risk 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 n=36 participants at risk ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMApp: Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
Renal and urinary disorders Worsened renal insufficiency	2.9% 1/35 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	0.00% 0/36 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Nervous system disorders Syncope	2.9% 1/35 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	0.00% 0/36 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Vascular disorders Death due to Hypotensive Shock	2.9% 1/35 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	0.00% 0/36 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Infections and infestations Death due to EVD	28.6% 10/35 • Number of events 10 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	5.6% 2/36 • Number of events 2 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Nervous system disorders Head Injury	2.9% 1/35 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	0.00% 0/36 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Infections and infestations Multi-organ failure due to EVD	5.7% 2/35 • Number of events 2 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	8.3% 3/36 • Number of events 3 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Infections and infestations Death due to sepsis	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Nervous system disorders Generalized seizure	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Vascular disorders Hypovolemic shock due to acute hemorrhage	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Gastrointestinal disorders Severe diarrhea	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Vascular disorders Arterial Hypertension	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Infections and infestations Hospitalization with febrile illness (malaria)	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.

Other adverse events

Measure	A/Current Standard of Care Alone n=35 participants at risk 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 n=36 participants at risk ZMapp (Trademark) + Optimized standard of care to include aggressive fluid resuscitation, hemodynamic support, and other interventions available in an optimized care setting. ZMApp: Triple monoclonal cocktail of antibodies against Zaire species of Ebola virus
Vascular disorders Hypotension	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	19.4% 7/36 • Number of events 7 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Infections and infestations Elevation in Fever	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	22.2% 8/36 • Number of events 8 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Vascular disorders Tachycardia	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	11.1% 4/36 • Number of events 4 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Respiratory, thoracic and mediastinal disorders Tachypnea	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	8.3% 3/36 • Number of events 3 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Vascular disorders Hypertension	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	8.3% 3/36 • Number of events 3 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Nervous system disorders Confusion	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	5.6% 2/36 • Number of events 2 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Nervous system disorders Seizure	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Respiratory, thoracic and mediastinal disorders Difficulty Breathing	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Infections and infestations Chills	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Gastrointestinal disorders Vomiting	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.
Nervous system disorders Agitation	0.00% 0/35 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.	2.8% 1/36 • Number of events 1 • 8 months, from March 2015 through November 2015 Only Serious Adverse Events and Infusion related events were recorded.

Additional Information

Dr. Richard T. Davey, Jr.

NIAID/LIR

Phone: 301-496-8029

Email: rdavey@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place