Dose Ranging Study of ALX-0171 in Infants Hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection
Condition: Respiratory Syncytial Virus Lower Respiratory Tract Infection
MeSH terms: Infections; Communicable Diseases; Respiratory Tract Infections
Intervention: ALX-0171 3.0 mg/kg; ALX-0171 6.0 mg/kg; ALX-0171 9.0 mg/kg; Placebo
Intervention MeSH terms: Gontivimab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 180.0
Sex: All
Minimum age: 28 Days
Maximum age: 2 Years
Healthy volunteers: No
Keywords: RSV, Lower Respiratory Tract Infection, pediattric patients

Summary:

      The primary objective is to evaluate the anti-viral effect and safety of different doses of
      inhaled ALX-0171 in subjects hospitalized for Respiratory Syncytial Virus Lower Respiratory
      Tract Infection (RSV LRTI). The secondary objective is to evaluate the clinical activity,
      pharmacokinetic (PK) properties, pharmacodynamic (PD) effect and immunogenicity of different
      doses of inhaled ALX-0171.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female infant or young child aged 28 days to < 2 years with gestational age ≥
             33 weeks at screening.

          2. Subject weighed between ≥ 3.0 kg and < 15.0 kg at screening.

          3. Subject is otherwise healthy but was hospitalized for and clinically diagnosed with
             RSV LRTI (bronchiolitis or broncho-pneumonia), i.e., showing typical clinical signs
             and symptoms such as tachypnea, wheezing, cough, crackles, use of accessory muscles
             and/or nasal flaring.

          4. Subject had a positive RSV diagnostic test at screening.

          5. Subject was expected to have to stay in the hospital for at least 24 hours (according
             to the Investigator's judgment at screening).

          6. Symptoms were likely related to RSV infection (i.e., the symptoms present needed to be
             probably linked to the current RSV infection according to Investigator's judgment) had
             appeared within 4 days of screening and were not yet improving at screening and
             randomization.

          7. Subject fulfilled at least 2 of the following RSV disease severity criteria at
             screening and randomization:

               -  Inadequate oral feeding that required feeding support (i.e., nasogastric tube or
                  intravenous [i.v.] line)

               -  Inadequate oxygen saturation defined as:

                    -  Oxygen saturation (peripheral capillary oxygen saturation [SpO2]) ≤ 92% on
                       room air or

                    -  Requiring oxygen supplementation to maintain oxygen saturation > 90% with
                       documented pre-supplementation value ≤ 92%

               -  Signs of respiratory distress defined as:

                    -  Respiratory rate ≥ 50 per minute in infants up to 12 months of age, and ≥ 40
                       per minute in children above 12 months and/or

                    -  Moderate or marked respiratory muscle retractions

          8. Normal psychomotor development.

        Exclusion Criteria:

          1. Subject was known to have significant comorbidities including:

               -  Genetic disorders (e.g., trisomy 21, cystic fibrosis),

               -  Hemodynamically significant congenital heart disease (e.g., needing corrective
                  therapy or inotropic support),

               -  Bronchopulmonary dysplasia,

               -  Any hereditary or acquired metabolic (bone) diseases,

               -  Hematologic or other malignancy.

          2. Subject was known to be human immunodeficiency virus (HIV)-positive. If the subject
             was < 6 months of age, a known HIV-positivity of the mother was also exclusionary.

          3. Subject was known to be immunocompromised.

          4. Subject had or was suspected to have an active, clinically relevant concurrent
             infection (e.g., bacterial pneumonia, urinary tract infection). Concurrent acute
             otitis media was not exclusionary.

          5. Subject had significant oral and/or maxillofacial malformations that would prevent
             proper positioning of the face mask.

          6. Subject received invasive mechanical ventilation or non-invasive respiratory support
             (i.e., continuous or bilevel positive airway pressure) in the 4 weeks prior to
             screening.

          7. During the admission, the subject was initially hospitalized in an intensive care unit
             (ICU) setting and/or had received invasive mechanical ventilation or non-invasive
             respiratory support (i.e., continuous or bilevel positive airway pressure).

          8. Subject was critically ill and/or was expected to require invasive mechanical
             ventilation, non invasive respiratory support (i.e., continuous or bilevel positive
             airway pressure), or High Flow oxygen therapy (HFOT) at levels not enabling
             nebulization therapy according to the Investigator's judgment. High Flow oxygen, with
             a maximum flow of 2 L/kg/min, was permitted under the following conditions:

               -  used as Standard of Care outside ICU setting

               -  could be removed for study drug administration (Note: oxygen flow at 2 L/min
                  could be provided)