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Safety of Nirsevimab for RSV in Infants with Heart or Lung Disease or Prematurity
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Design
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Preliminary results of an ongoing Phase 2/3 randomized, double-blind, controlled study
N= 925
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Objective
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To report the safety and pharmacokinetics of nirsevimab through the first respiratory syncytial virus (RSV) season in a study spanning two RSV seasons in preterm and chronic lung disease (CLD)-congenital heart disease (CHD) cohorts
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Study Groups
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Preterm cohort (n= 615)
Pavilizumab (n= 206)
Nirsevimab (n= 406)
CHD-CLD cohort (n= 310)
Pavilizumab (n= 98)
Nirsevimab (n= 208)
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Inclusion Criteria
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Preterm: first year of life and born 35 weeks or less; uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus; or aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone
CHD-CLD cohort: infants in their first year of life and documented, hemodynamically significant CHD or infants in their first year of life and a diagnosis of CLD of prematurity requiring medical intervention/management
Entering first RSV season at time of screening
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Exclusion Criteria
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Fever, acute illness, or hospitalization within 7 days of study; history or active of lower respiratory tract infection (LRTI); history or active RSV infection; renal/hepatic impairment; any condition that might interfere with study evaulation
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Methods
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Patients were randomized 2:1 to receive either single fixed intramuscular (IM) dose of nirsevimab, followed by 4 once-monthly IM dose of placebo one IM injection of nirsevimab 50 mg g (if< 5 kg) or 100 mg (if≥ 5 kg) or placebo; or pavilizumab 5 once-monthly IM dose of 15 mg/kg.
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Duration
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1 year |
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Outcome Measures
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Adverse events |
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Baseline Characteristics
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Pavilizumab (n= 309)
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Nirsevimab (n= 616)
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Age group
≤ 3 months
> 3 to ≤ 6 months
> 6 months
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46.6%
32.7%
20.7%
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44.5%
34.1%
21.4%
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Female
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43.0% |
48.2% |
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Weight group, day 1
< 5 kg
≥ 5 kg
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57.2%
42.8%
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56.1%
43.9%
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Gestational age, group
≥ 29 to < 32 weeks
≥ 32 to < 35 weeks
≥ 35 weeks
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23.0%
40.8%
13.6%
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20.8%
42.5%
15.6%
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Results
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Endpoint
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Preterm cohort (n= 615)
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CHD-CLD cohort (n= 310)
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Pavilizumab (n= 206)
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Nirsevimab (n= 406)
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Pavilizumab (n= 98)
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Nirsevimab (n= 208) |
| ≥ 1 adverse events |
134 (65.0%)
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268 (66.0%)
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72 (73.5%)
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148 (71.2%) |
| ≥ 1 treatment-emergent adverse events |
4 (1.9%)
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6 (1.5%)
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2 (2.0%)
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4 (1.9%) |
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≥ 1 adverse event of grade ≥ 3 severity
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7 (3.4%) |
14 (3.4%) |
13 (13.3%) |
30 (14.4%) |
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≥1 Treatment-related adverse event of grade ≥3 severity
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0 |
0 |
0 |
0 |
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Any adverse event with outcome of death*
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0 |
2 (0.5%) |
1 (1.0%) |
3 (1.4%) |
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≥ 1 serious adverse event
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11 (5.3%) |
28 (6.9%) |
20 (20.4%) |
40 (19.2%) |
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≥ 1 serious adverse event, grade ≥ 3 adverse event, or both
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11 (5.3%) |
28 (6.9%) |
21 (21.4%) |
45 (21.6%) |
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≥ 1 treatment-related serious adverse event
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0 |
0 |
0 |
0 |
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≥ 1 Adverse event of special interest**
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0 |
1 (0.2%) |
0 |
1 (0.5%) |
| ≥ 1 Covid-19–related adverse event |
1 (0.5%)
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8 (2.0%)
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1 (1.0%)
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2 (1.0%) |
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*All deaths were deemed unrelated to treatment by the investigator
**Includes hypersensitivity, immune complex disease, and thrombocytopenia
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Adverse Events
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Most common adverse events are infection and infestations, gastrointestinal disorders, administration site disorders |
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Study Author Conclusions
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N/A |
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InpharmD Researcher Critique
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This is a preliminary report of an ongoing two RSV season trial. The significance of the findings are to be confirmed once the full study is available. |