Evaluation of ALX-0171 in Japanese Children 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 1.5 mg/kg; Placebo
Intervention description: ALX-0171 1.5 mg/kg was administered via a single inhalation once daily for 3 consecutive days.; Placebo was administered via a single inhalation once daily for 3 consecutive days.
Intervention MeSH terms: Gontivimab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 15.0
Sex: All
Minimum age: 28 Days
Maximum age: 2 Years
Healthy volunteers: No

Summary:

      This was a randomized, double-blind, multicenter, Phase II study (NCT03418571) designed to
      support the selection of an optimal dose of inhaled ALX-0171 for further clinical
      development, taking ethnicity into consideration.

      Based on the results of the Phase IIb dose-ranging study ALX0171-C201 (RESPIRE), the Sponsor
      decided to discontinue ALX-0171 development in infants and to early terminate the
      ALX0171-C203 study.
    

Eligibility criteria:

        Main inclusion criteria:

          1. Subject was a Japanese male or female infant or young child aged 28 days to <2 years
             with gestational age ≥33 weeks at screening.

          2. Subject was of Japanese descent, i.e., born in Japan to Japanese parents and had
             Japanese maternal and paternal grandparents.

          3. Subject weighed between ≥3.0 kg and <15.0 kg at screening.

          4. Subject was 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.

          5. Subject had a positive RSV diagnostic test within 4 days of screening.

          6. Subject was expected to have to stay in the hospital for at least 24 hours (according
             to the Investigator's judgment at screening).

          7. Symptoms 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.

          8. Subject fulfilled at least two of the following RSV disease severity criteria at
             screening and randomization:

               -  Inadequate oral feeding that required feeding support (i.e., nasogastric tube or
                  i.v. line),

               -  Inadequate oxygen saturation defined as:

                    -  Peripheral capillary oxygen saturation (SpO2) <95% on room air, or

                    -  Requiring oxygen supplementation to maintain adequate oxygen saturation with
                       documented pre-supplementation value <95%

               -  Signs of respiratory distress defined as:

                    -  Respiratory rate ≥50 breaths per minute in infants up to 12 months of age,
                       and ≥40 breaths per minute in children above 12 months, and/ or

                    -  Moderate or marked respiratory muscle retractions

          9. Subject had normal psychomotor development.

        Others as defined in the protocol

        Main 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, 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 which would have
             prevented 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 current admission, subject was initially hospitalized in an Intensive Care
             Unit (ICU) setting and/or 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/minute
                  could be provided through the nebulizer)

          9. Subject had received 1 or more doses of palivizumab or treatment or prophylaxis with
             any RSV antiviral compound (e.g., ribavirin, i.v. immunoglobulin, or any
             investigational drug or vaccine for RSV [including subject's mother who had been
             vaccinated against RSV]) at any time prior to screening.

         10. Subject was required to continue or start systemic corticosteroid therapy. Subject on
             a maintenance therapy of inhaled corticosteroids could continue this treatment at the
             usual dose. Topical corticosteroids for skin disorders were permitted.

         11. Subject had clinically meaningful abnormalities on a 12-lead electrocardiogram (ECG),
             which according to the Investigor's judgement did not allow participation of the
             subject in the study. A 12-lead ECG performed within 4 days of screening was
             acceptable. If not available, the 12-lead ECG could be performed at the time of
             screening.

        Others as defined in the protocol