Safety, Tolerability and Pharmacokinetic First in Human (FIH) Study for Intravenous (IV) TKM-100802

NCT02041715 | Terminated Phase 1 DMC

• 1 other identifier: TKM-EBOV-002
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1, single-center, placebo-controlled, single-blind, first-in-human, single ascending dose (SAD) study followed by a multiple-dose cohort in healthy male and female subjects.

Conditions

Ebola Virus Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of TKM-100802

  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

  1 month

Study Arms (2)

TKM-100802 for Injection

EXPERIMENTAL

Drug: TKM-100802 for Injection

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

TKM-100802 for Injection DRUG

IV infusion

TKM-100802 for Injection

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 are able to read, review, agree to, and sign the informed consent document at Screening.
• Able to comply with all protocol-specified visit schedules and requirements.
• Healthy male and female subjects 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 (50 kg).
• a. Systolic blood pressure ≥110 mmHg (subject in the seated position and legs dangling) also, 5 minutes after moving from the supine to seated position any drop in systolic pressure must be \<15 mmHg and any increase in pulse \<10 bpm.
• \. Judged by the PI 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 PI and if judged not to be clinically significant, the subject may be considered for study participation.
• \. Adequate hepatic, renal, hematologic and clotting function as defined by total bilirubin, AST, ALT, serum creatinine, D-dimer and International normalized ratio (INR) within normal range as determined by the PI and Sponsor Medical Monitor.
• \. Female subjects 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 subjects 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 (2 separate forms of contraception, 1 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 study treatment. 8. Male subjects 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 study treatment.

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 according to the PI and Sponsor Medical Monitor preclude subject participation in the clinical study.
• Reports an uncontrolled psychiatric disorder or neurologic disease or seizure disorder not controlled by medication.
• Subject has a history of, or 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.
• 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).
• History of allergy to cosyntropin (MAD cohort only).
• Presence of any clinically significant results from laboratory tests, vital signs assessments and ECGs as judged by the PI.
• Reports receiving investigational drugs, biologics, or devices, or any antiviral drugs 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 or planned use during the course of the study.
• A medical condition requiring a prescription treatment which it would be unsafe to discontinue.
• Recent treatment with alternative therapies which, in the view of the PI or the Sponsor 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.

Sponsors & Collaborators

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

Study Sites (1)

Healthcare Discoveries, LLC d/b/a ICON Development Solutions

San Antonio, Texas, 78209, United States

Location

MeSH Terms

Conditions

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

Interventions

Injections; Saline Solution

Condition Hierarchy (Ancestors)

Infections

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Mark Kowalski, MD, PhD

  Arbutus Biopharma Corporation

  STUDY DIRECTOR

• Emanuel DeNoia, MD

  ICON Development Solutions

  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: January 9, 2014
• First Posted: January 22, 2014
• Study Start: January 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 7, 2015

Record last verified: 2015-08

Locations

US (1)