Safety and Pharmacokinetics of a Single ZMappTM Administration in Healthy Adult Volunteers

NCT02389192 | Withdrawn Phase 1

• 2 other identifiers: 15009415-I-0094
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: \- Ebola is a virus that can spread quickly and causes serious disease. It is currently causing an outbreak in West Africa. There are no approved treatments for Ebola. ZMappTM is a new drug made of natural infection-fighting substances. Researchers want to see if it can treat Ebola. Objective: \- To assess the safety of ZMappTM and how the body processes it. To measure the immune system response to ZMappTM. Eligibility: \- Healthy people 18 50 years old. Design:

• Participants will be screened with a medical history, physical exam, and blood and urine tests. They will have an electrocardiogram (ECG) to measure heart electrical activity. Small pads will be stuck to the arms, legs, and chest.
• Participants will be admitted to the hospital. They will have a physical exam, medication review, and blood samples.
• Two intravenous (IV) lines will be placed into separate arm veins. A needle will be used to guide plastic tubing into the veins. One will be used to take blood samples. The other will be used to give the study drug.
• Participants will be given drugs to help prevent side effects.
• Participants will be given the study drug by IV over 10 12 hours. Participants will be monitored closely and vital signs taken frequently. They may have another ECG.
• Blood samples will be taken before, during, and after the infusion.
• Participants will stay in the hospital 1 or 2 nights after receiving the drug.
• Participants will have several study visits over 90 days after getting the study drug. They will be asked about side effects. They may have a physical exam, and blood may be drawn.

Conditions

Healthy

Keywords

Ebola; Mono-clonal Antibody

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety of a single IV infusion of 50 mg/kg of ZMappTM

  at 8 time points through 90 days following infusion

• To determine serum pharmacokinetics following an intravenous (IV) infusion of 50 mg/kg of ZMappTM

  at 8 time points through 90 days following infusion

Secondary Outcomes (1)

• To assess the development of anti-drug antibodies (ADAs) elicited following a single IV infusion of 50 mg/kg of ZMappTM

  at 8 time points through 90 days following infusion

Study Arms (1)

OPEN

EXPERIMENTAL

healthy volunteers between the ages of 18-50 to receive a one-time infusion of Zmapp at a dose of 50mg/kg.

Drug: ZMAPP

Interventions

ZMAPP DRUG

ZMappTM, a combination of three mouse/human chimeric monoclonal antibodies (mAbs; c4G6, c2G4, and c13C6-FR1) directed against Ebola virus glycoprotein epitopes

OPEN

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult healthy volunteers 18 to 50 years of age, inclusive.
• Able to understand and provide written informed consent.
• Body mass index 18 kg/m2 to 29 kg/m2, inclusive, at time of screening.
• Female subjects must be of non-childbearing potential (e.g., be confirmed postmenopausal or have undergone surgical sterilization) or must, in conjunction with their sexual partner(s), use a highly effective contraceptive (namely, a long-acting reversible method (IUD, injectable, or implant), or a combination of oral contraception in conjunction with a male condom) during the screening period and for at least 30 days after the infusion of study medication.
• Male subjects must either be sterile or agree to use, for the entire duration of the study, a male condom; the female sexual partner must also use a medically acceptable form of birth control (e.g., oral contraceptives), or a highly effective contraceptive (as described in #4 above).
• Male subjects must agree to not donate sperm for at least 30 days after the infusion of study medication.

You may not qualify if:

• Pregnancy or breastfeeding.
• A positive urine or blood screen for drugs of abuse at time of screening.
• Prior use of any medical intervention involving antibody products.
• Active substance abuse or any medical or psychiatric condition that, in the opinion of the principal investigator, could jeopardize the subject's safety or the subject's ability to comply with the protocol requirements.
• Any chronic medical problem that requires daily medications (except Tylenol, oral contraceptives, vitamins, eye drops, and seasonal allergy medications), or other medical history that in the opinion of the investigator significantly increases the risk associated with a Phase 1 drug.
• Allergy or intolerance of antihistamines, acetominophen, or catabolic steroids.
• Active participation in any interventional clinical trial within 6 months prior to the dosing on Day 0 (i.e., received any other investigational drug).
• Prolonged QTcF interval \> 440 ms for males or \> 460 ms for females.
• Other clinically significant ECG abnormality, as determined by the principal investigator.
• Any clinically significant abnormal hematology, chemistry, coagulation, or urinalysis value, as determined by the principal investigator.
• Glomerular filtration rate (GFR) of \< 80 mL/min, based on the Modification of Diet in Renal Disease equation.
• Urine-albumin-to-creatinine ratio (UACR) \> 30 mg/g.
• Positive serology for Hepatitis B surface antigen
• Positive serology for Anti Hepatitis C Antibody
• Positive ELISA for HIV

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Interventions

ZMapp

Condition Hierarchy (Ancestors)

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

Study Officials

• Richard T Davey, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2015
• First Posted: March 17, 2015
• Study Start: March 11, 2015
• Primary Completion: December 27, 2017
• Study Completion: December 27, 2017
• Last Updated: December 16, 2019

Record last verified: 2017-12-27