Ebola Virus InfectionPhase 1NCT01518881
Safety, Tolerability and Pharmacokinetic First in Human (FIH) Study of Intravenous (IV) TKM-100201 Infusion
A Phase 1 study testing TKM-100201 in people with Ebola Virus Infection, run by Arbutus Biopharma Corporation at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Ebola Virus Infection
- What is being tested?
- TKM-100201
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Jul 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
- Reports an occupational health risk of exposure to Ebola virus known to be higher than that of the general population.
- Reports a known or suspected hypersensitivity or previous severe reactions to any of the constituents of the investigational product including oligonucleotide- or lipid-based products, liposomal drug products, and phospholipid-based products (parenteral nutrition, Intralipid).
- Reports a history of clinically significant allergies including food or drug allergies.
- Demonstrates a positive drug or alcohol screen.
- Reports a history of drug or alcohol addiction or abuse within the past 1 year.
- Subject is unwilling to limit alcohol consumption during the study (males: 2 drinks/day [30 g], <12 drinks/week [120 g] and females: 2 drinks/day [20 g], <12drinks/week [120 g]).
- Reports donating blood within 28 days prior to dosing. All volunteers will be advised not to donate blood for four weeks after completing the study.
- ports donating plasma (eg, plasmapheresis) within 14 days prior to dosing. All volunteers will be advised not to donate plasma for four weeks after completing the study.
- Demonstrates, in the opinion of study staff, veins unsuitable for repeated venipuncture or IV infusion (eg, veins difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture).
- Reports being capable of becoming pregnant, breastfeeding, or lactating.
- Demonstrates a positive pregnancy screen.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Placebo-Controlled, Single-Blind, Single-Ascending Dose Study With Additional Multiple-Ascending Dose Cohorts to Evaluate the Safety, Tolerability and Pharmacokinetics of TKM-100201 in Healthy Human Volunteers
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.
Read the detailed description
A maximum of 56 healthy adult (male and female) subjects will participate in this study, in two stages. In Stage 1, the Single-Ascending Dose (SAD) phase of the study will have up to six cohorts with 4 subjects (3 receiving TKM-100201 and 1 receiving saline placebo) in each cohort. Additional cohorts may be enrolled if a maximum tolerated dose (MTD) is not established after the initial six cohorts. In Stage 2, the Multiple-Ascending Dose (MAD) portion of the study will have up to three cohorts with four subjects (3 receiving TKM-100201 and 1 receiving saline placebo) in each cohort. Additional cohorts may be enrolled if a maximum tolerated dose (MTD) is not established after the initial three cohorts.
- Conditions
- Ebola Virus Infection
- Being tested
- TKM-100201, Placebo
- Medical subject headings
- Hemorrhagic Fever, Ebola
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TKM-100201Drug
Also called TKM-Ebola
IV Infusion
PlaceboDrug
Also called Normal Saline
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| TKM-100201 | Experimental | Not described Receives: Drug: TKM-100201 |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 month
Secondary outcomes (1)
Pharmacokinetics - Cmax, Tmax and AUC will be calculated
Time-points: Before infusion, mid-point of infusion, end of infusion and at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48 hours after infusion and day 7, day 10, day 15, day 22 and day 29.
Measured: 29 days post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionJul 2012
- Study completionJul 2012
Why it stopped: Corporate decision to reformulate the investigational product.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ebola Virus InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arbutus Biopharma Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Gregory M Haugen, M.D., Principal investigator, Cetero Research, San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01518881
- Sponsor's protocol ID
- TKM-EBOV-001
- Status last verified
- Jan 2014
- First submitted
- 8 Nov 2011
- Last updated
- 9 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled, Single-Blind, Single-Ascending Dose Study With Additional Multiple-Ascending Dose Cohorts to Evaluate the Safety, Tolerability and Pharmacokinetics of TKM-100201 in Healthy Human Volunteers
- ClinicalTrials.gov ID
- NCT01518881
- Acronym / sponsor ID
- TKM-EBOV-001
- Conditions
- Ebola Virus Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Corporate decision to reformulate the investigational product.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Arbutus Biopharma CorporationIndustry (pharma, biotech, devices)
- Collaborators
- United States Department of Defense
- Study start
- Jan 2012
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 26 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A maximum of 56 healthy adult (male and female) subjects will participate in this study, in two stages. In Stage 1, the Single-Ascending Dose (SAD) phase of the study will have up to six cohorts with 4 subjects (3 receiving TKM-100201 and 1 receiving saline placebo) in each cohort. Additional cohorts may be enrolled if a maximum tolerated dose (MTD) is not established after the initial six cohorts. In Stage 2, the Multiple-Ascending Dose (MAD) portion of the study will have up to three cohorts with four subjects (3 receiving TKM-100201 and 1 receiving saline placebo) in each cohort. Additional cohorts may be enrolled if a maximum tolerated dose (MTD) is not established after the initial three cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TKM-100201 | Experimental | Drug: TKM-100201 |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (26 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TKM-100201Also: TKM-EbolaIV Infusion | Drug | TKM-100201 |
| PlaceboAlso: Normal SalineIV infusion | Drug | Placebo |
Primary outcome
Safety and Tolerability of Treatment with TKM-100201
Time frame: 1 month
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 secondary outcome
Pharmacokinetics - Cmax, Tmax and AUC will be calculated
Time frame: 29 days post infusion
Results and safety
The study was stopped early (reason given: Corporate decision to reformulate the investigational product.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory M Haugen, M.D. principal investigator
Cetero Research, San Antonio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TKM-100201 in people with Ebola Virus Infection, run by Arbutus Biopharma Corporation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Corporate decision to reformulate the investigational product.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of Treatment with TKM-100201 (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2014.