A Study to Assess the Safety, Tolerability and Pharmacokinetics of AVI-7537 in Healthy Adult Volunteers

NCT01593072 | Withdrawn Phase 1 DMC

• 2 other identifiers: 7537-us-101W9113M-10-C-0056
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of healthy male and female subjects with intravenous (IV) infusions of AVI 7537 compared to matched placebo in and to evaluate the pharmacokinetics (PK).

Conditions

Ebola Hemorrhagic Fever

Keywords

Multiple Ascending Dose (MAD); Ebola Virus; Post Exposure Prophylaxis; EHF

Outcome Measures

Primary Outcomes (1)

• The outcome measures are Serial PK Day 1 over 24 hrs(pre-dose,10 min post,30 min post, 1hr 1.5,2,4,6, 8, 12,16,24,28,32,36, and 48 hrs post-dose), daily through level and on Day 14 (last day of dosing) serial PK until 48 hrs post last dose.

  The outcome measures are Serial PK Day 1 over 24 hours (pre-dose, 10 minutes post-dose , 30 minutes, 1 hour, 1.5, 2, 4, 6,. 8, 12,16,24 hours post-dose), daily trough level and on Day 14 (last day of dosing). PK Day 14 over 48 hours (post-dose, 10 minutes, 1.5, 2, 4, 6, 8, 12, 16, 24, 28, 32, 36, and 48 hours post-dose (collection of plasma pre-dose on Day 14 will also serve as the trough sample for that day).

  2 weeks

Secondary Outcomes (1)

• To evaluate the pharmacokinetics (PK) of 14 once daily doses of AVI-7537 in healthy male and female subjects,

  2 weeks

Study Arms (2)

AVI-7537

ACTIVE COMPARATOR

AVI-7537

Drug: AVI-7537

Placebo

OTHER

Normal Saline Solution (NSS)

Other: Normal Saline Solution (NSS)

Interventions

AVI-7537 DRUG

Cohort 1: AVI-7537 at 4.5 mg/kg IV; Cohort 2: AVI-7537 at 9 mg/kg IV;Cohort 3: AVI-7537 at 15 mg/kg IV; Cohort 4: AVI-7537 at 30 mg/kg IV The amount of AVI-7537 required to administer the required dose will be diluted to a volume of approximately 150 mL with normal saline solution (NSS) and given by IV infusion over 30 minutes once a day for 14 days. Infusions will be administered at approximately the same time each day.

AVI-7537

Normal Saline Solution (NSS) OTHER

Normal Saline Solution (NSS)

Placebo

Eligibility Criteria

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

You may qualify if:

• A subject must meet all of the following criteria to be eligible for this study.
• Man or woman 18 to 50 years of age, inclusive, at the time of screening.
• Body mass index 18 kg/m2 to 35 kg/m2, inclusive, at the time of screening and Check-in (Day -1).
• Good general health (no chronic health conditions) as determined by the Investigator.
• Female subjects must be of non-childbearing potential (e.g., be confirmed post-menopausal or have undergone surgical sterilization) or must, in conjunction with their sexual partner(s), use 2 forms of medically acceptable contraception (e.g., oral contraception in conjunction with a male condom) during the screening period and for the entire duration of the study including the 28-day post last dose follow-up.
• Male subjects must either be sterile or agree to use, for the entire duration of the study including the 28 day post last dose follow-up, a male condom and the female sexual partner must also use a medically acceptable form of birth control (e.g. oral contraceptives).
• Male subjects must agree to not donate sperm for at least 30 days after the last infusion of study medication.
• Able to understand the requirements of the study, to provide written informed consent (as evidenced by signature on an informed consent document that is approved by an Institutional Review Board \[IRB\]), and agreeable to abiding by the study restrictions.

You may not qualify if:

• A subject who meets any of the following criteria will be excluded from this study.
• Pregnancy or breastfeeding.
• A positive urine or blood screen for drugs of abuse, including alcohol.
• Use of any tobacco- or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to Check-in (Day -1).
• A positive cotinine test indicating recent nicotine use.
• Donated blood within 90 days or plasma within 30 days of first dose on Day 1.
• Active substance abuse or any medical or psychiatric condition that could jeopardize the subject's safety or the subject's ability to comply with the protocol.
• Use of any medications apart from vitamins, acetaminophen, or hormonal contraception within 14 days of first dose on Day 1. Subjects with mild seasonal allergies may use antihistamines at the discretion of the Investigator after approval by the Sponsor Medical Monitor.
• Participation in any interventional clinical trial within 45 days of first dose on Day 1 (i.e., received any other investigational drug).
• Recipient of an organ transplant (solid or hematopoietic).
• Prolonged QTcF interval \> 440 ms for males or \> 460 ms for females using the average of the triplicate electrocardiograms (ECGs) collected during screening, on Day -1, or just prior to dosing on Day 1.
• Other clinically significant ECG abnormality, as determined by the Investigator.
• Any clinically significant abnormal hematology, chemistry, coagulation, or urinalysis value, as determined by the 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.

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead
• United States Department of Defense: collaborator

Study Sites (1)

Quintiles Phase I Services

Overland Park, Kansas, 66211, United States

Location

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Alison Heald, MD

  Sarepta Therapeutics, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2012
• First Posted: May 7, 2012
• Study Start: August 1, 2012
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: January 24, 2013

Record last verified: 2013-01

Locations

US (1)