E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Syncytial Virus Lower Respiratory Tract Infection |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061603 |
E.1.2 | Term | Respiratory syncytial virus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the safety and tolerability of multiple doses of ALX-0171 |
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E.2.2 | Secondary objectives of the trial |
To evaluate the clinical effect of ALX-0171.
To explore the pharmacodynamics of ALX-0171
To explore the systemic pharmacokinetics of ALX-0171
To explore the immunogenicity of ALX-0171
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is a male or female infant or toddler aged 5 months to < 24 months. For the second part of the study, the subject's age can be between 3 and < 24 months,for the open-label lead-in, Part A, or 3 months to < 24 months for the double-blind part of the study, Part B. Upon implementation of a positive DMC recommendation, subjects may be aged 28 days to < 24 months in Part B. For the expansion cohort, Part C, the subject's age must be 28 days to < 5 months.
2. Subject weighs at least 3.5 kg.
3. Subject is otherwise healthy, but hospitalised for and clinically diagnosed with RSV LRTI (bronchiolitis or broncho-pneumonia), i.e., showing typical clinical signs and symptoms such as tachypnoea, wheezing, cough, crackles, use of accessory muscles, and/or nasal flaring.
4. Subject has appearance of symptoms that are likely related to RSV infection within ≤ 7 days at the time of screening, based on the investigator's judgement.
5. Subject has a positive RSV diagnostic test .
6. Subject is expected to have to stay in the hospital for at least 24 hours (according to the Investigator’s judgement at screening).
7. Subject has normal psychomotor development (according to the Investigator’s judgement at screening).
8. Subject’s gestational age was > 37 weeks.
9. Parent(s)/legal guardian(s) are able and willing to provide written informed consent.
10. The subject and parent(s)/legal guardian(s) are able and willing to comply with the study protocol. |
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E.4 | Principal exclusion criteria |
1. Subject has history of wheezing (i.e., >3 previous episodes of wheezing), as reported by the parent(s)/legal guardian(s), or according to the Investigator’s judgement at screening.
2. Subject is known to have significant comorbidities, including gastro-oesophageal reflux disease, genetic disorders (e.g., trisomy 21, cytic fibrosis), cardiopulmonary diseases (e.g., haemodynamically significant congenital heart disease, or bronchopulmonary dysplasia), any hereditary or acquired metabolic (bone) diseases, haematological or other malignancy, or is known to be human immunodeficiency virus (HIV) positive.
3. Subject is known to be immunocompromised.
4. Subject has any presence of active severe atopic dermatitis requiring daily use of topical anti-inflamatory (corticosteriod or equivalent).
5. Subject has any physician-confirmed food allergy.
6. Subject is suspected of having a clinically relevant infection other than RSV.
7. Subject received mechanical ventilation or long-term respiratory support in past 4 weeks prior to screnning.
8. Subject has significant oral and/or maxillofacial malformations.
9. Subject is critically ill and/or is expected to require invasive mechanical ventilation or non-invasive respiratory support (e.g., continuous or bi-level positive airway pressure, or high flow humidified nasal oxygen) within 24 hours (according to the Investigator’s judgement at screening), with the exception of O2 supplementation via nasal cannula, simple face mask, or headbox.
10. Subject has received 1 or more doses of palivizumab at any time prior to screening, or has received treatment with any antiviral therapy for RSV (e.g., ribavirin or i.v. immunoglobulin) within 1 month prior to screening. Subjects planned to receive palivizumab treatment or other RSV prophylaxis should not be included in the study.
11. Subject is being treated with corticosteroids and requires continued corticosteriod therapy.
12. Subject is being treated with antibiotics and needs continued antibiotic therapy. Note that subjects receiving antibiotics at screening will not be excluded if the antibiotics can be safely stopped according to the Investigator’s judgement. The initiation of antibiotic therapy during the study is allowed.
13. Subject is currently participating in any investigational study, or has previously participated in study ALX0171-C104. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety: Treatment emergent AEs, clinical laboratory test results (clinical chemistry and haematology), physical examination results including lung auscultation, and heart rate and SPO2 levels. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Clinical activity: feeding, respiratory rate, wheezing, crackles/crepitations, coughing, respiratory muscle retractions, general appearance
2) Exploratory pharmacokinetics: ALX-0171 in serum
3) Exploratory pharmacodynamics: viral load (nasal swabs), exploratory biomarkers in serum
4) Exploratory immunogenicity: ADA in serum |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
First part of the study is open-label lead-in part; second part is double-blind placebo-controlled |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Bulgaria |
Estonia |
Hungary |
Israel |
Latvia |
Malaysia |
Philippines |
Poland |
Slovakia |
Spain |
Thailand |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |