Safety and Efficacy of Pagibaximab Injection in Very Low Birth Weight Neonates for Prevention of Staphylococcal Sepsis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Phosphate Buffered Saline |
Drug: Placebo
Phosphate Buffered Saline on Days 0, 1, 2, 9, 16 and 23.
|
| Experimental: Pagibaximab 50 mg/mL Pagibaximab at 100 mg/kg intravenously at Days 0, 1, 2, 9, 16 and 23. |
Drug: Pagibaximab 50 mg/mL
Pagibaximab 100 mg/kg dosed on Days 0, 1, 2, 9, 16 and 23
|
Outcome Measures
Primary Outcome Measures
- The Number of Participants With Staphylococcal Sepsis From Study Days 0 to 35. [35 days]
Safety and efficacy
Eligibility Criteria
Criteria
Inclusion Criteria:
-
In-patient at a Neonatal Intensive Care Unit (NICU)
-
Informed consent obtained from the legally authorized representative
-
Less than 48 hours old at the time of first infusion
-
Birth weight between 600 grams and 1200 grams
-
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:
-
Infants with history of a hypersensitivity or severe vasomotor reaction to any antibody preparation.
-
Infants with proven staphylococcal infection prior to randomization.
-
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.
-
Immunodeficiency other than due to prematurity.
-
Currently receiving, recently received, or planned to receive other investigational agents that could interfere with conduct or results of this study.
-
Severe congenital or chromosomal anomaly that would limit life expectancy or required corrective measures during the period of this study
-
Uncontrolled seizures
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Biosynexus Incorporated | Gaithersburg | Maryland | United States | 20877 |
Sponsors and Collaborators
- Biosynexus Incorporated
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- MAB-N007
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Pagibaximab | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Period Title: Overall Study | ||
| STARTED | 792 | 787 |
| COMPLETED | 709 | 713 |
| NOT COMPLETED | 83 | 74 |
Baseline Characteristics
| Arm/Group Title | Pagibaximab | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Total of all reporting groups | ||
| Overall Participants | 792 | 787 | 1579 |
| Age (Weeks) [Mean (Standard Deviation) ] | |||
| 600-900g |
25.7
(1.67)
|
25.9
(1.83)
|
25.8
(1.76)
|
| 901-1200g |
28.0
(1.77)
|
27.9
(1.73)
|
28.0
(1.75)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
390
49.2%
|
393
49.9%
|
783
49.6%
|
| Male |
402
50.8%
|
394
50.1%
|
796
50.4%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
603
76.1%
|
596
75.7%
|
1199
75.9%
|
| Canada |
60
7.6%
|
59
7.5%
|
119
7.5%
|
| Spain |
54
6.8%
|
57
7.2%
|
111
7%
|
| Italy |
27
3.4%
|
30
3.8%
|
57
3.6%
|
| United Kingdom |
25
3.2%
|
28
3.6%
|
53
3.4%
|
| Germany |
23
2.9%
|
17
2.2%
|
40
2.5%
|
| Birth Weight (Number) [Number] | |||
| 600-900g |
381
48.1%
|
371
47.1%
|
752
47.6%
|
| 901-1200g |
411
51.9%
|
416
52.9%
|
827
52.4%
|
| Birth Weight (grams) [Mean (Standard Deviation) ] | |||
| 600-900g |
758.8
(90.28)
|
762.7
(85.05)
|
760.7
(87.70)
|
| 901-1200g |
1047.8
(86.25)
|
1039.0
(85.72)
|
1043.4
(86.05)
|
Outcome Measures
| Title | The Number of Participants With Staphylococcal Sepsis From Study Days 0 to 35. |
|---|---|
| Description | Safety and efficacy |
| Time Frame | 35 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| 1579 very low birth weight subjects were included in the ITT. |
| Arm/Group Title | Pagibaximab | Placebo |
|---|---|---|
| Arm/Group Description | ||
| Measure Participants | 792 | 787 |
| Number [Participants] |
85
10.7%
|
79
10%
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Pagibaximab | Placebo | ||
| Arm/Group Description | ||||
All Cause Mortality |
||||
| Pagibaximab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Pagibaximab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 284/784 (36.2%) | 273/778 (35.1%) | ||
| Blood and lymphatic system disorders | ||||
| Thrombocytopenia | 18/784 (2.3%) | 18 | 14/778 (1.8%) | 15 |
| Cardiac disorders | ||||
| Bradycardia | 4/784 (0.5%) | 4 | 4/778 (0.5%) | 4 |
| Congenital, familial and genetic disorders | ||||
| Patent Ductus Arteriosus | 104/784 (13.3%) | 104 | 110/778 (14.1%) | 110 |
| Gastrointestinal disorders | ||||
| Necrotizing Colitis | 52/784 (6.6%) | 52 | 42/778 (5.4%) | 42 |
| Intestinal Perforation | 28/784 (3.6%) | 28 | 26/778 (3.3%) | 28 |
| Metabolism and nutrition disorders | ||||
| Hyperkalaemia | 12/784 (1.5%) | 12 | 6/778 (0.8%) | 6 |
| Nervous system disorders | ||||
| Intraventricular Haemorrhage | 55/784 (7%) | 56 | 57/778 (7.3%) | 58 |
| Periventricular Leukomalacia | 14/784 (1.8%) | 14 | 15/778 (1.9%) | 15 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary Interstitial Emphysema | 26/784 (3.3%) | 27 | 23/778 (3%) | 25 |
| Pulmonary Haemorrhage | 9/784 (1.1%) | 9 | 12/778 (1.5%) | 12 |
Other (Not Including Serious) Adverse Events |
||||
| Pagibaximab | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 770/784 (98.2%) | 758/778 (97.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 479/784 (61.1%) | 646 | 487/778 (62.6%) | 665 |
| Endocrine disorders | ||||
| Hypothyroidism | 9/784 (1.1%) | 9 | 17/778 (2.2%) | 17 |
| Gastrointestinal disorders | ||||
| Gastrooesophageal Reflux Disease | 85/784 (10.8%) | 85 | 79/778 (10.2%) | 79 |
| Hepatobiliary disorders | ||||
| Hyperbilirubinaemia | 128/784 (16.3%) | 137 | 112/778 (14.4%) | 113 |
| Infections and infestations | ||||
| Ophthalmia Neonatorum | 56/784 (7.1%) | 58 | 41/778 (5.3%) | 48 |
| Investigations | ||||
| Cardiac Murmur | 48/784 (6.1%) | 50 | 45/778 (5.8%) | 49 |
| Metabolism and nutrition disorders | ||||
| Feeding Disorder Neonatal | 204/784 (26%) | 221 | 194/778 (24.9%) | 209 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Irwin Scher, MD |
|---|---|
| Organization | Biosynexus |
| Phone | 301-330-5800 |
| irwinscher@biosynexus.com |
- MAB-N007