Staphylococcal Sepsis
Conditions
Keywords
Staphylococcal, Coagulase Negative Staphylococcus, Monoclonal antibodies, Very Low Birth Weight Infants, Prophylaxis
Brief summary
Evaluate the safety, PK and efficacy comparing Pagibaximab Injection to placebo in preventing staphylococcal sepsis in very low birth weight infants. 1550 infants will be enrolled prior to 48 hours of life and will be randomized 1:1 to receive active drug or placebo on study days 0, 1, 2, 9, 16, and 23.
Detailed description
Phase 2b/3, randomized, double-blind, multicenter, placebo-controlled study evaluating the safety, efficacy and pharmacokinetics (PK) of pagibaximab (100 mg/kg/dose) in comparison to placebo for the prevention of staphylococcal sepsis in VLBW infants (600 -1200 grams). Subjects monitored for treatment related adverse events and tolerability to infusion of study drug. Neonatal sepsis will be assessed in the presence of clinical signs and symptoms and one blood culture positive for S. aureus or two blood cultures positive for Coagulase Negative Staphylococci (CoNS). The study period will be 35 days after the first dose or until, death, discharge, or transfer, whichever occurs first.
Interventions
DRUGPlacebo
Phosphate Buffered Saline on Days 0, 1, 2, 9, 16 and 23.
DRUGPagibaximab 50 mg/mL
Pagibaximab 100 mg/kg dosed on Days 0, 1, 2, 9, 16 and 23
Sponsors
Biosynexus Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 48 Hours
Healthy volunteers
Yes
Inclusion criteria
1. In-patient at a Neonatal Intensive Care Unit (NICU) 2. Informed consent obtained from the legally authorized representative 3. Less than 48 hours old at the time of first infusion 4. Birth weight between 600 grams and 1200 grams 5. Estimated gestation age ≤33 weeks For multiple gestations, twins may be enrolled if they each meet the entry criteria. They will both be assigned to the same treatment group.
Exclusion criteria
1. Infants with history of a hypersensitivity or severe vasomotor reaction to any antibody preparation. 2. Infants with proven staphylococcal infection prior to randomization. 3. Infants with a concomitant infection or other medical condition, whose participation, in the opinion of the Investigator and/or medical advisor, may create an unacceptable additional risk. 4. Immunodeficiency other than due to prematurity. 5. Currently receiving, recently received, or planned to receive other investigational agents that could interfere with conduct or results of this study. 6. Severe congenital or chromosomal anomaly that would limit life expectancy or required corrective measures during the period of this study 7. Uncontrolled seizures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Staphylococcal Sepsis From Study Days 0 to 35. | 35 days | Safety and efficacy |
Countries
United States
Participant flow
Recruitment details
The first subject was enrolled on 29 Mar 2009 and the last randomized subject completed the trial on 20 Jan 2011. The trial was conducted in the neonatal intensive care unit.
Participants by arm
| Arm | Count |
|---|---|
| Pagibaximab | 792 |
| Placebo | 787 |
| Total | 1,579 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 63 | 53 |
| Overall Study | Other Reason | 11 | 11 |
| Overall Study | Withdrawal by Subject | 9 | 10 |
Baseline characteristics
| Characteristic | Pagibaximab | Placebo | Total |
|---|---|---|---|
| Age Continuous 600-900g | 25.7 Weeks STANDARD_DEVIATION 1.67 | 25.9 Weeks STANDARD_DEVIATION 1.83 | 25.8 Weeks STANDARD_DEVIATION 1.76 |
| Age Continuous 901-1200g | 28.0 Weeks STANDARD_DEVIATION 1.77 | 27.9 Weeks STANDARD_DEVIATION 1.73 | 28.0 Weeks STANDARD_DEVIATION 1.75 |
| Birth Weight 600-900g | 758.8 grams STANDARD_DEVIATION 90.28 | 762.7 grams STANDARD_DEVIATION 85.05 | 760.7 grams STANDARD_DEVIATION 87.7 |
| Birth Weight 901-1200g | 1047.8 grams STANDARD_DEVIATION 86.25 | 1039.0 grams STANDARD_DEVIATION 85.72 | 1043.4 grams STANDARD_DEVIATION 86.05 |
| Region of Enrollment Canada | 60 participants | 59 participants | 119 participants |
| Region of Enrollment Germany | 23 participants | 17 participants | 40 participants |
| Region of Enrollment Italy | 27 participants | 30 participants | 57 participants |
| Region of Enrollment Spain | 54 participants | 57 participants | 111 participants |
| Region of Enrollment United Kingdom | 25 participants | 28 participants | 53 participants |
| Region of Enrollment United States | 603 participants | 596 participants | 1199 participants |
| Sex: Female, Male Female | 390 Participants | 393 Participants | 783 Participants |
| Sex: Female, Male Male | 402 Participants | 394 Participants | 796 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 770 / 784 | 758 / 778 |
| serious Total, serious adverse events | 284 / 784 | 273 / 778 |
Outcome results
Primary
The Number of Participants With Staphylococcal Sepsis From Study Days 0 to 35.
Safety and efficacy
Time frame: 35 days
Population: 1579 very low birth weight subjects were included in the ITT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pagibaximab | The Number of Participants With Staphylococcal Sepsis From Study Days 0 to 35. | 85 Participants |
| Placebo | The Number of Participants With Staphylococcal Sepsis From Study Days 0 to 35. | 79 Participants |