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Evaluation of ALX-0171 in Japanese Children Hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03418571
Recruitment Status : Terminated (The Sponsor decided to discontinue ALX-0171 development (due to insufficient evidence of efficacy). As a result, the ALX0171-C203 study was early terminated.)
First Posted : February 1, 2018
Results First Posted : July 15, 2019
Last Update Posted : July 30, 2019
Sponsor:
Information provided by (Responsible Party):
Ablynx

Tracking Information
First Submitted Date  ICMJE January 26, 2018
First Posted Date  ICMJE February 1, 2018
Results First Submitted Date  ICMJE May 2, 2019
Results First Posted Date  ICMJE July 15, 2019
Last Update Posted Date July 30, 2019
Actual Study Start Date  ICMJE March 1, 2018
Actual Primary Completion Date October 24, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
  • Safety and Tolerability of Inhaled ALX-0171 1.5 mg/kg as Measured by the Number of Subjects With at Least 1 Serious or Non-Serious Treatment-emergent Adverse Event (TEAE). [ Time Frame: From the subject's first study drug administration until completion of the subject's last visit, an average of 4 weeks ]
    Number of subjects reported with at least 1 serious or non-serious TEAEs in the ALX-0171 1.5 mg/kg treatment group and placebo treatment group.
  • Safety and Tolerability of Inhaled ALX-0171 1.5 mg/kg as Measured by the Number of Serious and Non-serious TEAEs. [ Time Frame: From the subject's first study drug administration until completion of the subject's last visit, an average of 4 weeks ]
    Number of serious and non-serious TEAEs reported in the ALX-0171 1.5 mg/kg treatment group and placebo treatment group.
Original Primary Outcome Measures  ICMJE
 (submitted: January 26, 2018)
Safety and tolerability as measured by the incidence of treatment-emergent (serious) adverse events [ Time Frame: From time of first dose to 28 days after first dose ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2018)
  • Pharmacokinetics as measured by the concentration of ALX-0171 in serum [ Time Frame: Day 2 - Day 3 ]
  • Time for viral load to drop below assay quantification limit (BQL) [ Time Frame: From day of first dose to 14 days after first dose ]
    Time needed for the viral load to drop below the assay quantification limit (time-to-BQL) in nasal swab specimens.
  • Global Severity Score [ Time Frame: From day of first dose to 14 days after first dose ]
    Evolution over time in Global Severity Score
  • Time to Clinical Response [ Time Frame: From day of first dose to 28 days after first dose ]
    Evaluation of the clinical response of the subjects as defined in the protocol
  • Immunogenicity as measured by the concentration of anti-ALX 0171 antibodies in serum [ Time Frame: From day of first dose to 28 days after first dose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of ALX-0171 in Japanese Children Hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection
Official Title  ICMJE A Randomized, Double-blind, Multicenter, Multiple-dose Study of ALX-0171 Versus Placebo Along With Standard of Care in Japanese Infants and Young Children Hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection
Brief 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.

Detailed Description

Four dose levels were planned to be evaluated in four consecutive cohorts consisting of Japanese infants and young children aged 28 days to <2 years with a gestational age ≥33 weeks who were hospitalized for and diagnosed with respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI):

  • Dose level 1: target dose of 1.5 mg/kg
  • Dose level 2: target dose of 3.0 mg/kg
  • Dose level 3: target dose of 6.0 mg/kg
  • Dose level 4: target dose of 9.0 mg/kg

Each cohort was planned to consist of 15 subjects enrolled and randomly assigned to receive ALX-0171 or placebo, in an allocation ratio of 4:1 (N = 12 active versus N = 3 placebo per cohort).

Due to early termination of the trial, only enrollment of Cohort 1 could be completed as planned. For Cohort 2, only 1 subject was screened but did not meet the eligibility criteria and was considered a screen failure. Therefore, data were not available for treatment groups ALX-0171 3.0 mg/kg, 6.0 mg/kg, and 9.0 mg/kg.

Of note, in line with applicable guidelines, an Independent Data Monitoring Committee (IDMC) was assigned to monitor the study. Upon completing of Cohort 1, the IDMC reviewed the available unblinded safety data and unanimously recommended to continue the study with no changes to the protocol.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Respiratory Syncytial Virus Lower Respiratory Tract Infection
Intervention  ICMJE
  • Biological: ALX-0171 1.5 mg/kg
    ALX-0171 1.5 mg/kg was administered via a single inhalation once daily for 3 consecutive days.
  • Other: Placebo
    Placebo was administered via a single inhalation once daily for 3 consecutive days.
Study Arms  ICMJE
  • Experimental: ALX-0171 1.5 mg/kg
    Intervention: Biological: ALX-0171 1.5 mg/kg
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 15, 2018)
15
Original Estimated Enrollment  ICMJE
 (submitted: January 26, 2018)
60
Actual Study Completion Date  ICMJE October 24, 2018
Actual Primary Completion Date October 24, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 2 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03418571
Other Study ID Numbers  ICMJE ALX0171-C203
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ablynx
Study Sponsor  ICMJE Ablynx
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Monitor Ablynx NV
PRS Account Ablynx
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP