A Phase I/II Multicentre Study in Otherwise Healthy Infants and Toddlers Hospitalised For and Diagnosed With RSV Lower Respiratory Tract Infection to Evaluate the Safety, Tolerability, and Clinical Activity of ALX-0171.

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2014-002841-23-GB
• Date of registration: 06/08/2014
• Prospective Registration: Yes
• Primary sponsor: Ablynx NV
• Public title: A Phase I/II Multicentre Study in Otherwise Healthy Infants and Toddlers Hospitalised For and Diagnosed With RSV Lower Respiratory Tract Infection to Evaluate the Safety, Tolerability, and Clinical Activity of ALX-0171.
• Scientific title: A Phase I/IIa Multicentre Study in Otherwise Healthy Infants and Toddlers Hospitalised For and Diagnosed With Respiratory Syncytial Virus Lower Respiratory Tract Infection, Consisting of an Open-label Lead in Part Followed by a Double-blind, Placebo-controlled Part, to Evaluate the Safety, Tolerability, and Clinical Activity of ALX-0171, Administered Via Inhalation, in Addition to Standard of Care
• Date of first enrolment: 22/09/2014
• Target sample size: 53
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002841-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: yes; Other trial design description: First part of the study is open-label lead-in part; second part is double-blind placebo-controlled; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Bulgaria, Estonia, Hungary, Israel, Latvia, Malaysia, Philippines, Poland, Slovakia, Spain, Thailand, United Kingdom

Contacts

• Name: [e-mail]
• Affiliation: Ablynx NV

• Name: [e-mail]
• Affiliation: Ablynx NV

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 53
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Respiratory Syncytial Virus Lower Respiratory Tract Infection
MedDRA version: 18.0 Level: PT Classification code 10061603 Term: Respiratory syncytial virus infection System Organ Class: 10021881 - Infections and infestations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Product Name: ALX-0171 Nanobody
Product Code: ALX-0171
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: not assigned yet
CAS Number: not assigned
Current Sponsor code: ALX-0171
Other descriptive name: ALX-0171 Nanobody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Nebuliser solution
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: day 0 to day 14

Secondary Objective: 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

Main Objective: To investigate the safety and tolerability of multiple doses of ALX-0171

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.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: day 0 to day 14

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

Secondary ID(s)

ALX0171-C104

Source(s) of Monetary Support

Ablynx NV

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 18/08/2016
• Date Completed: 17/02/2016
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002841-23/results