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Trial registered on ANZCTR


Registration number
ACTRN12610001043022
Ethics application status
Not yet submitted
Date submitted
24/11/2010
Date registered
29/11/2010
Date last updated
29/11/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Partially Blinded, Placebo-Controlled, Pharmacokinetic Study of Intravenously Administered BMS-943539-01-001 in Healthy Male Volunteers
Scientific title
A Phase 1, Partially Blinded, Placebo-Controlled, study of Intravenously Administered BMS-943539 to assess the pharmacokinetics and in particular the mean T-HALF of BMS-943539 across all doses in healthy male subjects.
Secondary ID [1] 253102 0
CA218-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pharmacokinetics of Intravenously Administered BMS-943539 in Healthy Male Volunteers.

BMS-943539 is an Adnectin (protein) which is specifically engineered to bind to Human Serum Albumin (HSA). 258658 0
Condition category
Condition code
Other 258862 258862 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All consented patients would be screened up to 14 days prior to randomization. At screening the patients will be assessed on their suitability to enter the study. Assessments preformed include: medical history, physical exam, laboratory assessment, ECG, concomitant and adverse events. Eligable subjects will be randomized.

Patients randomised to receive BMS-943539 will be administered the study drug via IV at day 1 and day 15 at different dose levels according to cohort. Cohort 1 will receive 0.1mg/kg. Cohort 2 will receive 0.3mg/Kg. Cohort 3 will receive 1.0mg/Kg

Patients will be observed after the 1st infusion on day 1 (observation period 1) and also after the second infusion day 15 (observation period 2).

After all the subjects in Cohort 1 have completed their Day 29 visits; the PK findings have been assessed (expected up to 4 weeks); and assuming criteria surpassing the defined no observed adverse event level (NOAEL) have not been met (see below), Cohort 2 will begin the study. Similarly, Cohort 3 will not begin until completion and PK assessment of Cohort 2, assuming the NOAEL has not been surpassed.
The NOAEL will be defined as the dose level 1 level below the lowest dose level in which either a) 2 or more actively treated (non-placebo) subjects experience any grade 2 National Cancer Institute (NCI; US)-Common Terminology Criteria for Adverse Events (CTCAE v4.03) BMS-943539-related toxicity or b) at least 1 actively treated subject experiences any grade greater than or equal to 3 BMS-943539-related toxicity.

The NOAEL will be the highest dose level completed if neither of these criteria is met. In the case that NOAEL criteria are surpassed in Cohorts 2 or 3, the next lower cohort will be declared the NOAEL and all remaining subjects
will be treated at the NOAEL, such that a total of 37 subjects (28 receiving BMS and 9 receiving placebo)
are treated in the study. This is in order to maintain the statistical precision sought to support the pharmacokinetic (PK) and immunogenicity research hypotheses, and to support an adequate number of subjects with safety observations. If the dose level of Cohort 1 is found to exceed the NOAEL, then no additional subjects will be dosed and the study will terminate.
Intervention code [1] 257620 0
Treatment: Drugs
Comparator / control treatment
All consented patients would be screened up to 14 days prior to randomization. At screening the patients will be assessed on their suitability to enter the study. Assessments preformed include: medical history, physical exam, laboratory assessment, ECG, concomitant and adverse events. Eligable subjects will be randomized.

Patients randomised to receive placebo will receive 0.9% sodium chloride placebo. This will be administered via IV at day 1 and day 15

Patients will be observed after the 1st infusion on day 1 (observation period 1) and also after the second infusion day 15 (observation period 2).
Control group
Placebo

Outcomes
Primary outcome [1] 259667 0
To assess the average time it takes for BMS-943539 to lose half of its pharmacologic activity (mean T-Half) following infusions on day 1 and day 15 in healthy male volunteers.

The mean T-Half will be assessed using Pharmacokinetic sampling and analysis.
Timepoint [1] 259667 0
PK samples will be collected on days 1 and 15 before infusion, 0.5 (mid-infusion) and 1 (end infusion), 1.5, 2, 3, 5, 7, 24, 48, 72, 96 or 120, and 168 hours after the start of each infusion. Also single random sample for BMS-943539 plasma concentration on after infusion on days 29, 36, 43, 50, and 57.
Secondary outcome [1] 266358 0
To assess the safety and tolerability of BMS-943539.

The following assessments will be used to determine the safety and tolerability; medical history, physical exam, vital signs, ECG, and safety laboratory assessments (biochemistry, haematology, coagulation panel, urinalysis).
Timepoint [1] 266358 0
Screening, day -1, day 1-6, day 8, day 14-20, day 22, day 29, day 36, day 43, day 50, day 57
Secondary outcome [2] 266365 0
To assess the immunogenicity of BMS-943539

Autoimmunity tests (ANA, C3, C4) will be performed.
Samples will be collected for the assessment of anti-BMS-943539 antibodies (anti-drug antibodies; ADA). Subjects with positive ADA results at Day 57 will be asked to return for follow-up assessment approximately every 28 days for ADA, ANA, C3, and C4 testing and immunological AE assessment until resolved, judged to be chronic or stable by the investigator, or the subject lost to follow-up.
Timepoint [2] 266365 0
Screening, day 1, day 15, day 22, day 29, day 43, day 57
Secondary outcome [3] 266366 0
To assess the effects of BMS-943539 on PR and QTc intervals

All ECGs will be 12-lead ECG recorded with the subject in the supine position. All ECGs are to be single assessments. Each individual ECG assessment must include assessment of heart rate and PR, QRS, QT, and QTcF (or QTcB) intervals. ECGs should be obtained prior to performing PK sample collection at the matching times.
Timepoint [3] 266366 0
Screening, day -1, day 1-2, day 14-16, day 29

Eligibility
Key inclusion criteria
1) Signed Written Informed Consent
a) The signed informed consent form.
2) Target Population
a) Healthy subjects as determined by no clinically significant deviation from normal
in medical history, physical examination, vital signs, electrocardiograms (ECGs),
and clinical laboratory determinations.
b) Not using prescription (including topical skin preparations other than nonprescription
moisturizers) or over-the-counter medications; herbal supplements;
or drugs of abuse, including alcohol and tobacco, for the duration of participation
in the study (screening duration plus 56 days following first administration of
blinded study treatment). (See also related exclusion criteria 2b, 2c, and 2f.)
c) Agree not to donate blood or plasma to any blood bank or for any purpose (other
than this study) for the duration of participation in the study (screening duration
plus 56 days following first administration of blinded study treatment). (See also
related exclusion criterion 2g.)
d) Body Mass Index (BMI) of 18 to 32 kg/m2 (BMI=weight (kg)/[height(m)]2) and
weight no less than 50 kg.
3) Age and Reproductive Status
a) Men, aged 18 to 60 years.
b) Subjects who are sexually active must agree to use a barrier method of
contraception during the study and for no less than 45 days following the last
dose.
Minimum age
18 Years
Maximum age
60 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Target Disease Exceptions
a) Chronic medical conditions requiring ongoing professional medical attention or treatment.
2) Medical History and Concurrent Diseases
a) Any history of autoimmune disease.
b) Recent (within 6 months) drug or alcohol abuse as defined by DSM IV, Diagnostic Criteria for Drug and Alcohol Abuse
c) Use of nicotine or tobacco containing products (including but not limited to: snuff, chewing tobacco, cigars, cigarettes, pipes, or nicotine patches) within 6 months prior to investigational product administration and during the study;
d) Major surgery within 6 months of treatment Day 1.
e) Concurrent or use within 12 months of treatment day 1 of corticosteroids or other immunosuppressant drugs, with the exception of inhaled or topical corticosteroids, for which there must be no concurrent use or use within 3 months of treatment day 1.
f) Use of prescription medication within 7 days or 5 x the elimination T-HALF, whichever is longer, before treatment Day 1.
g) Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration.
h) Blood transfusion within 4 weeks of study drug administration.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects will be allocated a randomization number by blinded site staff when they are randomized onto the study. This randomization number will be provided to the unblinded pharmacist who will have access to the randomization code list. The subjects randomization number will coincide with the randomization schedule that the unblinded pharmacist has and which describes which infusion the subject will receive - BMS-943539 or placebo. Each randomized subject will be assigned an infusion ( BMS-943539 or placebo) based on the information contained in the randomization schedule. Allocation is not concealed to the pharmacist but it is concealed to all other study staff including the patient.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A randomisation code will be generated by an unblinded independent statistician. This randomisation code list will be provided to the unblinded pharmacist. When the patient is randomised into the study, the blinded study team will assign each patient a randomisation number. The unblinded pharmacist will use the assigned randomisation number and the randomisation code list to determine the subject treatment assignment.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/01/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
37
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 258072 0
Commercial sector/Industry
Name [1] 258072 0
Bristol-Myers Squibb Australia
Country [1] 258072 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb Australia
Address
556 Princes Highway, Noble Park Victoria 3174
Country
Australia
Secondary sponsor category [1] 257263 0
None
Name [1] 257263 0
Address [1] 257263 0
Country [1] 257263 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 260067 0
Ethics committee address [1] 260067 0
Ethics committee country [1] 260067 0
Date submitted for ethics approval [1] 260067 0
24/11/2010
Approval date [1] 260067 0
Ethics approval number [1] 260067 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31919 0
Address 31919 0
Country 31919 0
Phone 31919 0
Fax 31919 0
Email 31919 0
Contact person for public queries
Name 15166 0
Patsy Recabarren
Address 15166 0
PRA International (ANZ)
Suite 1701, 323 Castlereagh Street
Sydney 2000, N.S.W Australia
Country 15166 0
Australia
Phone 15166 0
+61 (0)29289 8515
Fax 15166 0
+61 (0)29289 8501
Email 15166 0
RecabarrenPatsy@praintl.com
Contact person for scientific queries
Name 6094 0
Patsy Recabarren
Address 6094 0
PRA International (ANZ)
Suite 1701, 323 Castlereagh Street
Sydney 2000, N.S.W Australia
Country 6094 0
Australia
Phone 6094 0
+61 (0)29289 8515
Fax 6094 0
+61 (0)29289 8501
Email 6094 0
RecabarrenPatsy@praintl.com

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What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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