Safety, Tolerability and Pharmacokinetic First in Human (FIH) Study of Intravenous (IV) TKM-100201 Infusion

NCT01518881 | Terminated Phase 1 DMC

• 1 other identifier: TKM-EBOV-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, single-center, placebo-controlled, single-blind, first-in-human, single-ascending dose study with additional multiple-ascending dose cohorts in healthy male and female volunteers.

Conditions

Ebola Virus Infection

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of Treatment with TKM-100201

  Subjects will be monitored for treatment-emergent and dose-limiting toxicity (DLT). If there are any adverse events (changes from baseline in laboratory parameters, vitals and/or infusion reactions) during these monitoring periods, the Independent Safety Committee, will discuss the dosing of the remaining subjects. Before proceeding to the next dose cohort, the Independent Safety Committee will evaluate whether dose escalation will be permitted based on demonstration of adequate safety and tolerability.

  1 month

Secondary Outcomes (1)

• Pharmacokinetics - Cmax, Tmax and AUC will be calculated

  29 days post infusion

Study Arms (2)

TKM-100201

EXPERIMENTAL

Drug: TKM-100201

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

TKM-100201 DRUG

IV Infusion

Also known as: TKM-Ebola

TKM-100201

Placebo DRUG

IV infusion

Also known as: Normal Saline

Placebo

Eligibility Criteria

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

You may qualify if:

• Informed of the nature of the study and have agreed to and are able to read, review and sign the informed consent document at screening. The informed consent document will be written in English, therefore the volunteer must have the ability to read and communicate in English.
• Able to comply with all protocol-specified visit schedules and requirements.
• Completed the screening process within 14 days prior to dosing.
• Healthy male and female volunteers 18 to 50 years of age, inclusive, at the time of dosing.
• Body mass index (BMI) between 22 kg/m2 to 35 kg/m2, inclusive, and weigh at least 110 lbs.
• Judged by an Investigator to be in good health as documented by the medical history, physical examination (including but may not be limited to an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems), vital sign assessments, 12-lead ECG, clinical laboratory assessments, and by general observations. Any abnormalities or deviations outside the normal ranges for any of clinical testing (laboratory tests, ECG, vital signs) can be repeated at the discretion of the Investigator(s) and judged to be not clinically significant for study participation.
• Adequate hepatic, renal, hematologic and clotting function as defined by total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine, D-dimer and International normalized ratio (INR) within normal range as determined by the Investigator(s) and Sponsor Medical Monitor.
• Female volunteers must be one of the following:
• naturally postmenopausal (no menses) for \> 2 years and has a documented FSH level \>40 mIU/mL; or
• have a documented history of ovarian failure; or
• surgically postmenopausal (bilateral oophorectomy or hysterectomy). Female volunteers that are surgically postmenopausal must provide documentation of the bilateral oophorectomy or hysterectomy prior to Day 1 dosing to be eligible for participation in the study; or
• Women of childbearing potential (FSH ≤40 mIU/mL) must have negative serum hCG at screening, a negative urine pregnancy test prior to the first study treatment, and must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, or have a vasectomized partner) from screening throughout the duration of study treatment and for 1 month after the last administration of investigational product.
• Male volunteers who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening throughout the duration of study treatment and for 1 month after the last dose of investigational product.

You may not qualify if:

• Evidence or history of clinically significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic or allergic disease at screening or medication for comorbidity which, in dialogue between the Investigator and Medical Monitor would preclude subject participation in the clinical trial.
• Reports an uncontrolled psychiatric disorder or neurologic disease or seizure disorder not controlled by medication.
• Subject has a history of existing clinically significant cardiovascular disease (for example, uncontrolled hypertension, unstable angina, congestive heart failure or serious cardiac arrhythmias). In addition New York Heart Association Functional Classification Class II or greater will be excluded (see Appendix).
• Reports history of coronary heart disease (CHD), CHD-equivalent disease or CHD risk \>20% as designated by the National Cholesterol Education Program Adult Treatment Panel III.
• Current diagnosis or known history of liver disease (e.g. acute or chronic hepatitis or liver cirrhosis).
• Presence of any clinically significant results from laboratory tests, vital signs assessments and ECGs as judged by the Investigator(s).
• Reports receiving any antiviral drugs, investigational drugs, biologics, or devices within 28 days prior to study treatment or planned use during the course of the study.
• Reports receiving naturopathic medications, herbal supplements, or lipid lowering therapies within 28 days prior to study treatment of planned use during the course of the study.
• Recent treatment with alternative therapies which, in the view of the Investigator(s) or the Medical Monitor, could potentially confound clinical and laboratory assessments.
• Demonstrates a marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval \>450 ms)
• Reports concomitant use of any medication that prolongs the QT/QTc interval.
• Reports a history of additional risk factors for torsades de pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome).
• When confirmed upon additional testing, demonstrates a reactive screen for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody.
• Reports infections requiring antibiotic therapy within 30 days of screening (as determined by the Investigator\[s\]).
• Reports a history of Ebola virus exposure.

Sponsors & Collaborators

• Arbutus Biopharma Corporation: lead
• United States Department of Defense: collaborator

Study Sites (1)

Cetero Research

Fargo, North Dakota, 58104, 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

• Gregory M Haugen, M.D.

  Cetero Research, San Antonio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2011
• First Posted: January 26, 2012
• Study Start: January 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: January 9, 2014

Record last verified: 2014-01

Locations

US (1)