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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001651-49 | EudraCT Number |
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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.
This was a Phase 2b, randomized, double-blind, placebo-controlled, international, multicenter dose-ranging study in infants and toddlers hospitalized for RSV LRTI. The study evaluated 3 dose levels of ALX-0171 in a sequential part (safety Cohorts 1-3) followed by a parallel part (Cohort 4).
An Independent Data Monitoring Committee (IDMC) was assigned to review study data and provide recommendations on proceeding to the next safety cohort and on which dose levels could be taken forward in the parallel part.
Three dose levels of ALX-0171 were evaluated:
The study drug was administered by inhalation once daily for 3 consecutive days along with standard of care treatment, which was determined by the Investigator (or his/her designee) according to institutional practice.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALX-0171 3.0 mg/kg | Experimental | Inhalation of ALX-0171 3.0 mg/kg once daily for 3 consecutive days |
|
| ALX-0171 6.0 mg/kg | Experimental | Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days |
|
| ALX-0171 Dose 9.0mg/kg | Experimental | Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
|
| Placebo | Placebo Comparator | Inhalation of Placebo once daily for 3 consecutive days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ALX-0171 3.0 mg/kg | Biological |
| ||
| ALX-0171 6.0 mg/kg |
| Measure | Description | Time Frame |
|---|---|---|
| Time for Viral Load to Drop Below Assay Quantification Limit (BQL) (Plaque Assay Analysis) | The primary endpoint for this trial was the time needed for the viral load to drop below the quantification limit (time-to-BQL) of the plaque assay in nasal mid-turbinate swab specimens. Time-to-BQL was defined as the time from the first study drug administration to the first occurrence of a value below the quantification limit (BQL), provided the next measured value was also below the limit of quantification. The time to BQL for subjects with missing data and/or who did not reach BQL during the trial were censored at the last non-missing viral load assessment. The primary endpoint was analysed using logrank test to compare time-to-BQL between each of the ALX-0171 treatment groups and the combined placebo group. The tests were performed in a sequential way to preserve the family-wise error rate at 0.05. The comparisons were performed in the following order: ALX-0171 9 mg/kg vs Placebo, followed by ALX-0171 6mg/kg vs Placebo, ALX-0171 3mg/kg vs Placebo. | Overall Study Period (i.e., approximately 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Global Severity Score on Day 2 (5 Hours Post-dose) | A formal comparison for change from Baseline in GSS to Day 2, 5 hours post-dose was performed using a contrast analysis on a longitudinal mixed model with random factor subject and fixed effects baseline value, treatment group and timepoint, including the treatment-by-timepoint interaction term. All data up to and including Day 3 were used in the longitudinal mixed model. The Kenward-Roger approximation of degrees of freedom was used. The model was fitted using an unstructured variance-covariance matrix. The individual pair-wise comparisons were reported (comparison in least square [LS] means for 9.0 mg/kg versus placebo; 6.0mg/kg versus placebo; 3.0 mg/kg versus placebo). Evolution over time in Global Severity Score. The maximum total score is 20 (minimum:0 to manimum:20); higher score indicates more severe disease. |
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Inclusion Criteria:
Male or female infant or young child aged 28 days to < 2 years with gestational age ≥ 33 weeks at screening.
Subject weighed between ≥ 3.0 kg and < 15.0 kg at screening.
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.
Subject had a positive RSV diagnostic test at screening.
Subject was expected to have to stay in the hospital for at least 24 hours (according to the Investigator's judgment at screening).
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.
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:
Signs of respiratory distress defined as:
Normal psychomotor development.
Exclusion Criteria:
Subject was known to have significant comorbidities including:
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.
Subject was known to be immunocompromised.
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.
Subject had significant oral and/or maxillofacial malformations that would prevent proper positioning of the face mask.
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.
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).
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:
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| Name | Affiliation | Role |
|---|---|---|
| Ablynx Clinical Department | Ablynx, a Sanofi company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator site 2 | Brussels | Belgium | ||||
| Investigator site |
A total of 301 subjects were screened.180 subjects were randomized to receive ALX-0171 3.0 mg/kg, ALX-0171 6.0 mg/kg, ALX-0171 9.0 mg/kg or placebo, yielding an overall allocation ratio of 3:1 active to placebo.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Inhalation of Placebo once daily for 3 consecutive days |
| FG001 | ALX-0171 3.0 mg/kg | Inhalation of ALX-0171 3.0 mg/kg once daily for 3 consecutive days |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 30, 2017 | May 22, 2019 |
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|
| ALX-0171 9.0 mg/kg | Biological |
|
| Placebo | Other |
|
|
| from Baseline untill Day 2 (5 hours post-dose) |
| Time-to-Clinical Response | The time-to-clinical response was defined as the time between the first study drug administration and the time of achieving adequate oxygen saturation (defined as SpO2 > 92% over a period of at least 4 hours) and adequate oral feeding (which is sufficient to maintain sufficient hydration, in the judgment of the Investigator). | Overall Study Period (i.e., approximately 28 days) |
| Time-to-BQL (RT-qPCR) | As secondary endpoint, the time-to-BQL using RT-qPCR was summarized using Kaplan Meier (KM) estimates. No p-values were calculated. For RSV load by RT-qPCR, the lower limit of quantification (LLOQ) was 2.4 log10 copies/mL. The upper limit confidence interval (CI) could not be calculated; Values of the 25 percentile are reported here. | Overall Study Period (i.e., approximately 28 days) |
| Time-to-undetectable Viral Load (Plaque Assay Analysis) | The time-to-undetectability (hours), defined as the time from the first study drug administration to the first occurrence of viral titer below the lower limit of quantification (LLOQ), and target not detected provided the next measured value was also below the quantification limit and undetected, were summarized using KM estimates, based on the plaque assay. The time-to-event for subjects with missing data and/or subjects who did not reach undetectability during the trial were censored at the last non-missing viral load assessment. For RSV load by plaque assay the LLOQ was 1.7 log10 pfu/mL. | Overall Study Period (i.e., approximately 28 days) |
| Viral Load Changes From Baseline (Plaque Assay Analysis) | Change from Baseline in RSV Load measured by Plaque Assay (RSV Infected Population) | From Baseline until Day 14 (Follow-up) (Baseline; Day 1, 5 hours post-dose; Day 3, 2 hours post-dose; and Follow-up reported) |
| Viral Load Changes From Baseline (RT-qPCR Analysis) | Change from Baseline in RSV Load measured by RT-qPCR (RSV Infected Population) | From Baseline until Day 14 (Follow-up) (Baseline; Day 1, 5 hours post-dose; Day 3, 2 hours post-dose; and Follow-up reported) |
| Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | The time-weighted average change from baseline to Day x was defined as (AUCx - x* viral load at baseline) /x, where AUCx denotes the AUC between baseline and Day x. For subjects who only had data up to Day t (t\ | From Baseline until Day 14 (Follow-up) (Baseline, Day 3, and Follow-up reported) |
| Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | The time-weighted average change from baseline to Day x was defined as (AUCx - x* viral load at baseline) /x, where AUCx denotes the AUC between baseline and Day x. For subjects who only had data up to Day t (t\ | From Baseline until Day 14 (Follow-up) (Baseline, Day 3, and Follow-up reported) |
| Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | The number of subjects with treatment-emergent (TE) anti-drug antibodies (ADA; TE ADA) based on ADA assay by treatment group for the Safety Population. Blood samples for immunogenicity assessments were collected at Baseline and on Day 14. Immunogenicity data were analyzed using the Safety Population. This population differs from the ITT and mITT Populations as 2 subjects who were originally randomized to placebo, received active treatment once; one subject received ALX-0171 6.0 mg/kg and one subject ALX-0171 9.0 mg/kg. | Overall Study Period (i.e., approximately 28 days) |
| Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Number of subjects with treatment-emergent neutralizing antibodies (TE NAb) as detected with the competitive ligand binding NAb assay. Blood samples for immunogenicity assessments were collected at Baseline and on Day 14. Immunogenicity data were analyzed using the Safety Population. This population differs from the ITT and mITT Populations as 2 subjects who were originally randomized to placebo, received active treatment once; one subject received ALX-0171 6.0 mg/kg and one subject ALX-0171 9.0 mg/kg. | Overall Study Period (i.e., approximately 28 days) |
| Brussels |
| Belgium |
| Investigator Site | Edegem | Belgium |
| Investigator Site | Leuven | Belgium |
| Investigator site | Roeselare | Belgium |
| Investigator Site | Kozloduy | Bulgaria |
| Investigator Site | Plovdiv | Bulgaria |
| Investigator Site | Rousse | Bulgaria |
| Investigator Site | Sofia | Bulgaria |
| Investigator Site | Stara Zagora | Bulgaria |
| Investigator Site | Santiago | Chile |
| Investigator site | Valdivia | Chile |
| Investigator site | Cali | Colombia |
| Investigator Site | Floridablanca | Colombia |
| Investigator Site 1 | Medellín | Colombia |
| Investigator site 2 | Medellín | Colombia |
| Investigator site | Čakovec | Croatia |
| Investigator site | Osijek | Croatia |
| Investigator site | Slavonski Brod | Croatia |
| Investigator site | Varaždin | Croatia |
| Investigator site 1 | Zagreb | Croatia |
| Investigator site 2 | Zagreb | Croatia |
| Investigator site 3 | Zagreb | Croatia |
| Investigator site 4 | Zagreb | Croatia |
| Investigator site | Hradec Králové | Czechia |
| Investigator Site | Tartu | Estonia |
| Investigator site | Bochum | Germany |
| Investigator site | Dresden | Germany |
| Investigator Site | Sankt Augustin | Germany |
| Investigator Site | Wuppertal | Germany |
| Investigator Site | Balassagyarmat | Hungary |
| Investigator site 1 | Budapest | Hungary |
| Investigator Site 2 | Budapest | Hungary |
| Investigator Site 3 | Budapest | Hungary |
| Investigator Site 4 | Budapest | Hungary |
| Investigator site | Debrecen | Hungary |
| Investigator Site | Szeged | Hungary |
| Investigator site | Székesfehérvár | Hungary |
| Investigator Site | Veszprém | Hungary |
| Investigator site | Beersheba | Israel |
| Investigator site | Haifa | Israel |
| Investigator site | Petah Tikva | Israel |
| Investigator Site | Daugavpils | Latvia |
| Investigator Site | Riga | Latvia |
| Investigator site | George Town | Malaysia |
| Investigator Site | Kuala Lumpur | Malaysia |
| Investigator Site | Seremban | Malaysia |
| Investigator Site | Sibu | Malaysia |
| Investigator Site | Alabang | Philippines |
| Investigator site | Manila | Philippines |
| Investigator Site 1 | Quezon City | Philippines |
| Investigator Site 2 | Quezon City | Philippines |
| Investigator site | Lublin | Poland |
| Investigator site | Trzebnica | Poland |
| Investigator site | Banská Bystrica | Slovakia |
| Investigator site | Bratislava | Slovakia |
| Investigator site | Košice | Slovakia |
| Investigator Site | Poprad | Slovakia |
| Investigator Site 1 | Barcelona | Spain |
| Investigator Site 2 | Barcelona | Spain |
| Investigator Site 3 | Barcelona | Spain |
| Investigator Site | Bilbao | Spain |
| Investigator Site | El Palmar | Spain |
| Investigator site 1 | Madrid | Spain |
| Investigator Site 2 | Madrid | Spain |
| Investigator Site | Málaga | Spain |
| Investigator site | Santiago de Compostela | Spain |
| Investigator site | Seville | Spain |
| Investigator Site | Valencia | Spain |
| Investigator Site 1 | Bangkok | Thailand |
| Investigator site 2 | Bangkok | Thailand |
| Investigator Site | Chiang Mai | Thailand |
| Investigator site | Hat Yai | Thailand |
| Investigator Site | Khon Kaen | Thailand |
| FG002 | ALX-0171 6.0 mg/kg | Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days |
| FG003 | ALX-0171 9.0mg/kg | Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
|
| Included in the mITT Population | modified ITT (mITT): All randomized subjects who received at least 1 study drug administration. |
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| Included in the Safety Population | Safety: All subjects who received at least 1 study drug administration, as treated. |
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| COMPLETED |
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| NOT COMPLETED |
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|
modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized).
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Inhalation of Placebo once daily for 3 consecutive days |
| BG001 | ALX-0171 3.0 mg/kg | Inhalation of ALX-0171 3.0 mg/kg once daily for 3 consecutive days |
| BG002 | ALX-0171 6.0 mg/kg | Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days |
| BG003 | ALX-0171 9.0mg/kg | Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | The age reported is the age at the time of informed consent signing. | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Mean | Standard Deviation | months |
| |||||||||||||
| Age, Customized | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Count of Participants | Participants |
| |||||||||||||||
| Age, Customized | Age, Customized; Gestational Age | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Mean | Standard Deviation | Weeks |
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| Sex: Female, Male | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Count of Participants | Participants |
| |||||||||||||||
| Ethnicity (NIH/OMB) | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Count of Participants | Participants |
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| Race/Ethnicity, Customized | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Count of Participants | Participants |
| |||||||||||||||
| Region of Enrollment | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Count of Participants | Participants |
| |||||||||||||||
| Number of days between symtpom onset and the first dose of study drug | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Mean | Standard Deviation | days |
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| Global Severity Score (GSS) | The GSS is a composite score based on the ReSVinet Scale (Justicia-Grande et al., 2016) that allowed for objective categorization of infants with respiratory infections based on seven different items (i.e., feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnea, general condition, and fever). The sum of the sub-item scores provides the GSS total score (range: 0-20). Higher score indicates more severe disease. | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Mean | Standard Deviation | score on a scale |
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| Respiratory Distress Instrument (RDAI) | The RDAI instrument is a 17-point scoring system based on wheezing and retraction. The sum of the subscores provides the RDAI total score, with total range 0 to 17. Higher scores indicating more severe disease. | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Mean | Standard Deviation | score on a scale |
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| Height | Mean | Standard Deviation | centimetres |
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| Weight | Mean | Standard Deviation | kilograms |
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| Weight category | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Time for Viral Load to Drop Below Assay Quantification Limit (BQL) (Plaque Assay Analysis) | The primary endpoint for this trial was the time needed for the viral load to drop below the quantification limit (time-to-BQL) of the plaque assay in nasal mid-turbinate swab specimens. Time-to-BQL was defined as the time from the first study drug administration to the first occurrence of a value below the quantification limit (BQL), provided the next measured value was also below the limit of quantification. The time to BQL for subjects with missing data and/or who did not reach BQL during the trial were censored at the last non-missing viral load assessment. The primary endpoint was analysed using logrank test to compare time-to-BQL between each of the ALX-0171 treatment groups and the combined placebo group. The tests were performed in a sequential way to preserve the family-wise error rate at 0.05. The comparisons were performed in the following order: ALX-0171 9 mg/kg vs Placebo, followed by ALX-0171 6mg/kg vs Placebo, ALX-0171 3mg/kg vs Placebo. | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Posted | Median | 95% Confidence Interval | hours | Overall Study Period (i.e., approximately 28 days) |
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| Secondary | Change From Baseline in Global Severity Score on Day 2 (5 Hours Post-dose) | A formal comparison for change from Baseline in GSS to Day 2, 5 hours post-dose was performed using a contrast analysis on a longitudinal mixed model with random factor subject and fixed effects baseline value, treatment group and timepoint, including the treatment-by-timepoint interaction term. All data up to and including Day 3 were used in the longitudinal mixed model. The Kenward-Roger approximation of degrees of freedom was used. The model was fitted using an unstructured variance-covariance matrix. The individual pair-wise comparisons were reported (comparison in least square [LS] means for 9.0 mg/kg versus placebo; 6.0mg/kg versus placebo; 3.0 mg/kg versus placebo). Evolution over time in Global Severity Score. The maximum total score is 20 (minimum:0 to manimum:20); higher score indicates more severe disease. | Posted | Least Squares Mean | Standard Error | score on a scale | from Baseline untill Day 2 (5 hours post-dose) |
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| Secondary | Time-to-Clinical Response | The time-to-clinical response was defined as the time between the first study drug administration and the time of achieving adequate oxygen saturation (defined as SpO2 > 92% over a period of at least 4 hours) and adequate oral feeding (which is sufficient to maintain sufficient hydration, in the judgment of the Investigator). | modified Intent-to-Treat Population (mITT): All randomized subjects who received at least 1 study drug administration. In this population, the subjects were classified as randomized (i.e.,using the treatment to which the subject was randomized). | Posted | Median | 95% Confidence Interval | hours | Overall Study Period (i.e., approximately 28 days) |
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| Secondary | Time-to-BQL (RT-qPCR) | As secondary endpoint, the time-to-BQL using RT-qPCR was summarized using Kaplan Meier (KM) estimates. No p-values were calculated. For RSV load by RT-qPCR, the lower limit of quantification (LLOQ) was 2.4 log10 copies/mL. The upper limit confidence interval (CI) could not be calculated; Values of the 25 percentile are reported here. | The modified ITT (mITT) population consisted of all randomized subjects who received at least 1 administration of study drug. When using this population, the subjects were classified as randomized (i.e., using the treatment to which the subject was randomized). | Posted | Median | 95% Confidence Interval | hours | Overall Study Period (i.e., approximately 28 days) |
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| Secondary | Time-to-undetectable Viral Load (Plaque Assay Analysis) | The time-to-undetectability (hours), defined as the time from the first study drug administration to the first occurrence of viral titer below the lower limit of quantification (LLOQ), and target not detected provided the next measured value was also below the quantification limit and undetected, were summarized using KM estimates, based on the plaque assay. The time-to-event for subjects with missing data and/or subjects who did not reach undetectability during the trial were censored at the last non-missing viral load assessment. For RSV load by plaque assay the LLOQ was 1.7 log10 pfu/mL. | RSV-Infected Population: A central RSV test was used for defining the RSV-Infected population. The RSV-Infected population consisted of all randomized subjects with RSV infection, as confirmed by RT-qPCR (hVIVO quantitative PCR assay) on Day 1 (pre- or post-dose), who received at least 1 administration of study drug. | Posted | Median | 95% Confidence Interval | hours | Overall Study Period (i.e., approximately 28 days) |
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| Secondary | Viral Load Changes From Baseline (Plaque Assay Analysis) | Change from Baseline in RSV Load measured by Plaque Assay (RSV Infected Population) | RSV-Infected Population: A central RSV test was used for defining the RSV-Infected population. The RSV-Infected population consisted of all randomized subjects with RSV infection, as confirmed by RT-qPCR (hVIVO quantitative PCR assay) on Day 1 (pre- or post-dose), who received at least 1 administration of study drug. | Posted | Mean | Standard Error | log10 pfu/mL | From Baseline until Day 14 (Follow-up) (Baseline; Day 1, 5 hours post-dose; Day 3, 2 hours post-dose; and Follow-up reported) |
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| Secondary | Viral Load Changes From Baseline (RT-qPCR Analysis) | Change from Baseline in RSV Load measured by RT-qPCR (RSV Infected Population) | RSV-Infected Population: A central RSV test was used for defining the RSV-Infected population. The RSV-Infected population consisted of all randomized subjects with RSV infection, as confirmed by RT-qPCR (hVIVO quantitative PCR assay) on Day 1 (pre- or post-dose), who received at least 1 administration of study drug. | Posted | Mean | Standard Error | log10 copies/mL | From Baseline until Day 14 (Follow-up) (Baseline; Day 1, 5 hours post-dose; Day 3, 2 hours post-dose; and Follow-up reported) |
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| Secondary | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | The time-weighted average change from baseline to Day x was defined as (AUCx - x* viral load at baseline) /x, where AUCx denotes the AUC between baseline and Day x. For subjects who only had data up to Day t (t\ | RSV-Infected Population: A central RSV test was used for defining the RSV-Infected population. The RSV-Infected population consisted of all randomized subjects with RSV infection, as confirmed by RT-qPCR (hVIVO quantitative PCR assay) on Day 1 (pre- or post-dose), who received at least 1 administration of study drug. | Posted | Mean | Standard Error | log10 pfu/mL | From Baseline until Day 14 (Follow-up) (Baseline, Day 3, and Follow-up reported) |
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| Secondary | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | The time-weighted average change from baseline to Day x was defined as (AUCx - x* viral load at baseline) /x, where AUCx denotes the AUC between baseline and Day x. For subjects who only had data up to Day t (t\ | RSV-Infected Population: A central RSV test was used for defining the RSV-Infected population. The RSV-Infected population consisted of all randomized subjects with RSV infection, as confirmed by RT-qPCR (hVIVO quantitative PCR assay) on Day 1 (pre- or post-dose), who received at least 1 administration of study drug. | Posted | Mean | Standard Error | log10 copies/mL | From Baseline until Day 14 (Follow-up) (Baseline, Day 3, and Follow-up reported) |
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| Secondary | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | The number of subjects with treatment-emergent (TE) anti-drug antibodies (ADA; TE ADA) based on ADA assay by treatment group for the Safety Population. Blood samples for immunogenicity assessments were collected at Baseline and on Day 14. Immunogenicity data were analyzed using the Safety Population. This population differs from the ITT and mITT Populations as 2 subjects who were originally randomized to placebo, received active treatment once; one subject received ALX-0171 6.0 mg/kg and one subject ALX-0171 9.0 mg/kg. | The Safety Population consisted of all subjects who received at least 1 administration of study drug. When using this population, the subjects were classified as treated (i.e., using the treatment that the subject actually received). Number of subjects with non-missing ADA results were: placebo:39; ALX-0171 3.0mg/kg:45; 6.0mg/kg:44; 9.0mg/kg:46. | Posted | Count of Participants | Participants | Overall Study Period (i.e., approximately 28 days) |
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| Secondary | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Number of subjects with treatment-emergent neutralizing antibodies (TE NAb) as detected with the competitive ligand binding NAb assay. Blood samples for immunogenicity assessments were collected at Baseline and on Day 14. Immunogenicity data were analyzed using the Safety Population. This population differs from the ITT and mITT Populations as 2 subjects who were originally randomized to placebo, received active treatment once; one subject received ALX-0171 6.0 mg/kg and one subject ALX-0171 9.0 mg/kg. | The Safety Population consisted of all subjects who received at least 1 administration of study drug. When using this population, the subjects were classified as treated (i.e., using the treatment that the subject actually received).Number of subjects with non-missing NAb results were: placebo:39; ALX-0171 3.0mg/kg:45; 6.0mg/kg:44; 9.0mg/kg:46. | Posted | Count of Participants | Participants | Overall Study Period (i.e., approximately 28 days) |
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All adverse events (AEs) were reported from first study drug intake to the end of study visit (Day 28) or withdrawal visit.
A treatment-emergent AE (TEAE) was defined as any AE starting or worsening in severity (for preexisting conditions) from the start of study drug administration, until completion of the subject's last visit.
Adverse event data were analyzed using the Safety Population. This population differs from the ITT and mITT Populations as 2 subjects who were originally randomized to placebo, received active treatment once; one subject received ALX-0171 6.0 mg/kg and one subject ALX-0171 9.0 mg/kg.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Inhalation of Placebo once daily for 3 consecutive days | 0 | 40 | 5 | 40 | 17 | 40 |
| EG001 | ALX-0171 3.0 mg/kg | Inhalation of ALX-0171 3.0 mg/kg once daily for 3 consecutive days | 0 | 45 | 4 | 45 | 16 | 45 |
| EG002 | ALX-0171 6.0 mg/kg | Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days | 0 | 44 | 3 | 44 | 16 | 44 |
| EG003 | ALX-0171 9.0mg/kg | Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days | 0 | 46 | 3 | 46 | 10 | 46 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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| Vessel puncture site phlebitis | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Pneumonia bacterial | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Bronchiolitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Pneumonococcal bacteraemia | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Respiratory syncytial virus infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Pneumonia viral | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
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| Rhinorrhea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (21.0) | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Conjuctivitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
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Publication of any results from this study will be according to the principles of the Declaration of Helsinki, and will require prior review and written agreement of the Sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Monitor | Ablynx NV | +32 (0)9262 00 00 | clinicaltrials@ablynx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 31, 2018 | May 22, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000712591 | gontivimab |
Not provided
Not provided
Not provided
| Between 18 and 65 years |
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| >=65 years |
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| ≥ 6 months and < 12 months |
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| ≥ 12 months |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Black or African American |
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| Multiple |
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| Other |
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| White |
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| Bulgaria |
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| Chile |
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| Colombia |
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| Croatia |
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| Germany |
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| Hungary |
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| Israel |
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| Latvia |
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| Malaysia |
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| Philippines |
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| Poland |
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| Slovakia |
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| Spain |
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| Thailand |
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| ≥ 4.0 kg and < 5.0 kg |
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| ≥ 5.0 kg and < 7.0 kg |
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| ≥ 7.0 kg and < 10.0 kg |
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| ≥ 10.0 kg and < 12.0 kg |
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| ≥ 12.0 kg and < 15.0 kg |
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The primary endpoint was analysed using log-rank test to compare time-to-BQL between each of the ALX-0171 treatment groups and the combined placebo group. The tests were performed in a sequential way to preserve the family-wise error rate at 0.05.
| Log Rank |
| =0.001 |
| Superiority |
| The primary endpoint was analysed using log-rank test to compare time-to-BQL between each of the ALX-0171 treatment groups and the combined placebo group. The tests were performed in a sequential way to preserve the family-wise error rate at 0.05. | Log Rank | <0.001 | Superiority |
| OG003 | ALX-0171 9.0mg/kg | Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
|
|
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Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
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Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
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|
Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days |
| OG003 | ALX-0171 9.0mg/kg | Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
|
|
Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days
|
|
|
|
| ALX-0171 9.0mg/kg |
Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
|
|
| ALX-0171 9.0mg/kg |
Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
|
|
Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days |
| OG003 | ALX-0171 9.0mg/kg | Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
|
|
Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days |
| OG003 | ALX-0171 9.0mg/kg | Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days |
|
|