Safety Study of Anti-Influenza Virus Monoclonal Antibody to Treat Influenza

Phase 1 Study of TCN-032 (Human Monoclonal Antibody Directed Against the M2 Protein of Influenza A Virus) in Healthy Adult Volunteers

The purpose of this study is to compare the safety profile in healthy volunteers of a single intravenous administration of TCN-032 as compared with placebo.

Study Overview

• Status: Completed
• Conditions: Influenza, Human
• Intervention / Treatment: Biological: TCN-032; Biological: Placebo

Detailed Description

Influenza is a highly communicable acute respiratory disease that is considered to be one of the major infectious disease threats to the human population. Annual vaccination is generally effective only against those strains included in the vaccine. Because of the frequent emergence of divergent variants and the periodic emergence of strains with novel hemagglutinin and/or neuraminidase surface proteins that can result in global pandemics, the availability of potent antiviral agents for the prevention and/or treatment of influenza remains an urgent clinical and public health priority.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • SNBL Clinical Pharmacology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers
• Normal lab tests

Exclusion Criteria:

• Prior treatment with a monoclonal antibody

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Biological: Placebo; Placebo - 0.9% Sodium Chloride for Injection, USP
EXPERIMENTAL: TCN-032	Biological: TCN-032; TCN-032 is a human monoclonal antibody that specifically binds to a conserved epitope of the amino-terminal extracellular domain (M2e) of the influenza virus matrix protein 2 (M2). The drug is intended for use as an antiviral agent for the treatment of disease caused by type A influenza viruses. Treatments within the study will consist of single ascending dose-escalation ranging from 1 to 40 mg/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment - number of participants with adverse events (AE)	Safety will be assessed by physical examinations, vital signs, serial electrocardiograms and clinical laboratory tests (hematology, chemistry and urinalysis). A clinically significant laboratory value will be any abnormal result that is an unexpected or unexplained laboratory value or change in value from the patient's prior values. AEs will be reported by severity and relatedness to study treatment and classified according to MedDRA	60 days post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic analysis (PK)- Evaluate the single, ascending dose PK of TCN-032	PK evaluation of TCN-032 plasma concentrations will include: tmax (time at which maximum concentration is observed),Cmax (maximum observed concentration), t1/2 (terminal-elimination half-life), CL (clearance), Vd (volume of distribution).	60 days post infusion
Immunogenicity - detect and measure generation of anti-drug antibodies (ADA)specific for TCN-032	Immunogenicity will be assessed based on induction of TCN-032 anti-drug antibodies. Baseline and serial post-treatment serum measures of anti-TCN-032 antibodies will be detected by immunoassay and summarized by dose and time point with means, standard deviations, medians, quartiles, and ranges. Change from baseline in anti-TCN-032 antibody levels will be similarly analyzed.	60 days post infusion

Collaborators and Investigators

• Sponsor: Theraclone Sciences, Inc.
• Investigators: Principal Investigator: Mohamed Al-Ibrahim, MD, FACP, SNBL

Publications and helpful links

General Publications

• Grandea AG 3rd, Olsen OA, Cox TC, Renshaw M, Hammond PW, Chan-Hui PY, Mitcham JL, Cieplak W, Stewart SM, Grantham ML, Pekosz A, Kiso M, Shinya K, Hatta M, Kawaoka Y, Moyle M. Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12658-63. doi: 10.1073/pnas.0911806107. Epub 2010 Jul 1.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: July 5, 2011
• First Submitted That Met QC Criteria: July 7, 2011
• First Posted (ESTIMATE): July 8, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): April 2, 2012
• Last Update Submitted That Met QC Criteria: March 30, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Influenza
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: TCN-032-001