Respiratory Syncytial Virus Lower Respiratory Tract Infection
Conditions
Keywords
RSV, Lower Respiratory Tract Infection, pediattric patients
Brief summary
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.
Detailed description
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: * Dose 1: target dose of 3.0 mg/kg * Dose 2: target dose of 6.0 mg/kg * Dose 3: target dose of 9.0 mg/kg 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.
Interventions
BIOLOGICALALX-0171 3.0 mg/kg
BIOLOGICALALX-0171 6.0 mg/kg
BIOLOGICALALX-0171 9.0 mg/kg
OTHERPlacebo
Sponsors
Ablynx, a Sanofi company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
28 Days to 2 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female infant or young child aged 28 days to \< 2 years with gestational age ≥ 33 weeks at screening. 2. Subject weighed between ≥ 3.0 kg and \< 15.0 kg at screening. 3. 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. 4. Subject had a positive RSV diagnostic test at screening. 5. Subject was expected to have to stay in the hospital for at least 24 hours (according to the Investigator's judgment at screening). 6. 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. 7. 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: * Oxygen saturation (peripheral capillary oxygen saturation \[SpO2\]) ≤ 92% on room air or * Requiring oxygen supplementation to maintain oxygen saturation \> 90% with documented pre-supplementation value ≤ 92% * Signs of respiratory distress defined as: * Respiratory rate ≥ 50 per minute in infants up to 12 months of age, and ≥ 40 per minute in children above 12 months and/or * Moderate or marked respiratory muscle retractions 8. Normal psychomotor development.
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, a 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 that would prevent 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 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). 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/min could be provided)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time for Viral Load to Drop Below Assay Quantification Limit (BQL) (Plaque Assay Analysis) | Overall Study Period (i.e., approximately 28 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Global Severity Score on Day 2 (5 Hours Post-dose) | from Baseline untill 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. |
| Time-to-Clinical Response | Overall Study Period (i.e., approximately 28 days) | 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). |
| Time-to-BQL (RT-qPCR) | Overall Study Period (i.e., approximately 28 days) | 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. |
| Time-to-undetectable Viral Load (Plaque Assay Analysis) | Overall Study Period (i.e., approximately 28 days) | 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. |
| Viral Load Changes From Baseline (Plaque Assay Analysis) | From Baseline until Day 14 (Follow-up) (Baseline; Day 1, 5 hours post-dose; Day 3, 2 hours post-dose; and Follow-up reported) | Change from Baseline in RSV Load measured by Plaque Assay (RSV Infected Population) |
| Viral Load Changes From Baseline (RT-qPCR Analysis) | From Baseline until Day 14 (Follow-up) (Baseline; Day 1, 5 hours post-dose; Day 3, 2 hours post-dose; and Follow-up reported) | Change from Baseline in RSV Load measured by RT-qPCR (RSV Infected Population) |
| Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | From Baseline until Day 14 (Follow-up) (Baseline, Day 3, and Follow-up reported) | 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\<x), the endpoint was defined as (AUCt - t\*viral load at baseline) / t. |
| Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | From Baseline until Day 14 (Follow-up) (Baseline, Day 3, and Follow-up reported) | 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\<x), the endpoint was defined as (AUCt - t\*viral load at baseline) / t. |
| Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Overall Study Period (i.e., approximately 28 days) | 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. |
| Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Overall Study Period (i.e., approximately 28 days) | 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. |
Countries
Belgium, Bulgaria, Chile, Colombia, Croatia, Czechia, Estonia, Germany, Hungary, Israel, Latvia, Malaysia, Philippines, Poland, Slovakia, Spain, Thailand
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Inhalation of Placebo once daily for 3 consecutive days | 42 |
| ALX-0171 3.0 mg/kg Inhalation of ALX-0171 3.0 mg/kg once daily for 3 consecutive days | 45 |
| ALX-0171 6.0 mg/kg Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days | 43 |
| ALX-0171 9.0mg/kg Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days | 45 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Parent/guardian withdrew consent | 2 | 1 | 1 | 1 |
| Overall Study | Randomized but received no study drug | 1 | 1 | 0 | 0 |
| Overall Study | Subject left country after Day14 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | ALX-0171 3.0 mg/kg | ALX-0171 9.0mg/kg | Total | ALX-0171 6.0 mg/kg | Placebo |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 45 Participants | 45 Participants | 175 Participants | 43 Participants | 42 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 6.933 months STANDARD_DEVIATION 5.8827 | 7.022 months STANDARD_DEVIATION 5.6884 | 6.896 months STANDARD_DEVIATION 5.9234 | 6.657 months STANDARD_DEVIATION 6.2605 | 6.964 months STANDARD_DEVIATION 6.0668 |
| Age, Customized Age categories ≥ 12 months | 9 Participants | 8 Participants | 36 Participants | 9 Participants | 10 Participants |
| Age, Customized Age categories < 6 months | 23 Participants | 25 Participants | 99 Participants | 27 Participants | 24 Participants |
| Age, Customized Age categories ≥ 6 months and < 12 months | 13 Participants | 12 Participants | 40 Participants | 7 Participants | 8 Participants |
| Age, Customized Gestational Age | 38.6 Weeks STANDARD_DEVIATION 1.99 | 38.3 Weeks STANDARD_DEVIATION 1.54 | 38.5 Weeks STANDARD_DEVIATION 1.73 | 38.6 Weeks STANDARD_DEVIATION 1.62 | 38.5 Weeks STANDARD_DEVIATION 1.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 18 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 40 Participants | 157 Participants | 38 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Global Severity Score (GSS) | 9.2 score on a scale STANDARD_DEVIATION 2 | 9.4 score on a scale STANDARD_DEVIATION 2.41 | 9.2 score on a scale STANDARD_DEVIATION 2.23 | 9.3 score on a scale STANDARD_DEVIATION 2.09 | 9.1 score on a scale STANDARD_DEVIATION 2.44 |
| Height | 65.71 centimetres STANDARD_DEVIATION 10.21 | 66.55 centimetres STANDARD_DEVIATION 9.58 | 65.85 centimetres STANDARD_DEVIATION 9.915 | 65.25 centimetres STANDARD_DEVIATION 10.19 | 65.84 centimetres STANDARD_DEVIATION 9.997 |
| Number of days between symtpom onset and the first dose of study drug | 3.34 days STANDARD_DEVIATION 1.144 | 3.25 days STANDARD_DEVIATION 1.149 | 3.25 days STANDARD_DEVIATION 1.088 | 3.23 days STANDARD_DEVIATION 0.845 | 3.16 days STANDARD_DEVIATION 1.207 |
| Race/Ethnicity, Customized Race Asian | 7 Participants | 10 Participants | 27 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Race Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Multiple | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 3 Participants | 4 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race White | 38 Participants | 32 Participants | 141 Participants | 36 Participants | 35 Participants |
| Region of Enrollment Belgium | 3 Participants | 1 Participants | 9 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Bulgaria | 8 Participants | 11 Participants | 32 Participants | 6 Participants | 7 Participants |
| Region of Enrollment Chile | 0 Participants | 4 Participants | 4 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Colombia | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Croatia | 6 Participants | 3 Participants | 23 Participants | 8 Participants | 6 Participants |
| Region of Enrollment Germany | 0 Participants | 2 Participants | 6 Participants | 3 Participants | 1 Participants |
| Region of Enrollment Hungary | 6 Participants | 4 Participants | 25 Participants | 8 Participants | 7 Participants |
| Region of Enrollment Israel | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Latvia | 1 Participants | 5 Participants | 10 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Malaysia | 4 Participants | 3 Participants | 14 Participants | 3 Participants | 4 Participants |
| Region of Enrollment Philippines | 1 Participants | 3 Participants | 5 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Poland | 5 Participants | 0 Participants | 13 Participants | 3 Participants | 5 Participants |
| Region of Enrollment Slovakia | 0 Participants | 2 Participants | 4 Participants | 2 Participants | 0 Participants |
| Region of Enrollment Spain | 7 Participants | 1 Participants | 15 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Thailand | 2 Participants | 5 Participants | 10 Participants | 1 Participants | 2 Participants |
| Respiratory Distress Instrument (RDAI) | 8.41 score on a scale STANDARD_DEVIATION 4.07 | 8.11 score on a scale STANDARD_DEVIATION 3.8 | 8.44 score on a scale STANDARD_DEVIATION 3.693 | 8.74 score on a scale STANDARD_DEVIATION 3.19 | 8.5 score on a scale STANDARD_DEVIATION 3.74 |
| Sex: Female, Male Female | 15 Participants | 17 Participants | 75 Participants | 19 Participants | 24 Participants |
| Sex: Female, Male Male | 30 Participants | 28 Participants | 100 Participants | 24 Participants | 18 Participants |
| Weight | 7.188 kilograms STANDARD_DEVIATION 2.2278 | 7.020 kilograms STANDARD_DEVIATION 2.2474 | 7.066 kilograms STANDARD_DEVIATION 2.3059 | 6.988 kilograms STANDARD_DEVIATION 2.4084 | 7.065 kilograms STANDARD_DEVIATION 2.4193 |
| Weight category ≥ 10.0 kg and < 12.0 kg | 4 Participants | 1 Participants | 18 Participants | 7 Participants | 6 Participants |
| Weight category ≥ 12.0 kg and < 15.0 kg | 1 Participants | 2 Participants | 4 Participants | 0 Participants | 1 Participants |
| Weight category ≥ 3.0 kg and < 4.0 kg | 2 Participants | 2 Participants | 5 Participants | 0 Participants | 1 Participants |
| Weight category ≥ 4.0 kg and < 5.0 kg | 6 Participants | 7 Participants | 34 Participants | 13 Participants | 8 Participants |
| Weight category ≥ 5.0 kg and < 7.0 kg | 15 Participants | 14 Participants | 55 Participants | 11 Participants | 15 Participants |
| Weight category ≥ 7.0 kg and < 10.0 kg | 17 Participants | 19 Participants | 59 Participants | 12 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 45 | 0 / 44 | 0 / 46 |
| other Total, other adverse events | 17 / 40 | 16 / 45 | 16 / 44 | 10 / 46 |
| serious Total, serious adverse events | 5 / 40 | 4 / 45 | 3 / 44 | 3 / 46 |
Outcome results
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.
Time frame: Overall Study Period (i.e., approximately 28 days)
Population: 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).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time for Viral Load to Drop Below Assay Quantification Limit (BQL) (Plaque Assay Analysis) | 46.1 hours |
| ALX-0171 3.0 mg/kg | Time for Viral Load to Drop Below Assay Quantification Limit (BQL) (Plaque Assay Analysis) | 14.2 hours |
| ALX-0171 6.0 mg/kg | Time for Viral Load to Drop Below Assay Quantification Limit (BQL) (Plaque Assay Analysis) | 5.1 hours |
| ALX-0171 9.0mg/kg | Time for Viral Load to Drop Below Assay Quantification Limit (BQL) (Plaque Assay Analysis) | 5.1 hours |
Comparison: 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.p-value: <0.001Log Rank
Comparison: 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.p-value: =0.001Log Rank
Comparison: 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.p-value: <0.001Log Rank
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.
Time frame: from Baseline untill Day 2 (5 hours post-dose)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Global Severity Score on Day 2 (5 Hours Post-dose) | -3.6392 score on a scale | Standard Error 0.416 |
| ALX-0171 3.0 mg/kg | Change From Baseline in Global Severity Score on Day 2 (5 Hours Post-dose) | -3.8548 score on a scale | Standard Error 0.4103 |
| ALX-0171 6.0 mg/kg | Change From Baseline in Global Severity Score on Day 2 (5 Hours Post-dose) | -4.1296 score on a scale | Standard Error 0.4129 |
| ALX-0171 9.0mg/kg | Change From Baseline in Global Severity Score on Day 2 (5 Hours Post-dose) | -4.2844 score on a scale | Standard Error 0.4099 |
Comparison: A 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 + 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.p-value: =0.271Mixed Models Analysis
p-value: =0.404Mixed Models Analysis
p-value: =0.713Mixed Models Analysis
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.
Time frame: Overall Study Period (i.e., approximately 28 days)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Total TE ADA Positive | 10 Participants |
| Placebo | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Total TE ADA Negative | 16 Participants |
| Placebo | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | TE ADA Equivocal | 12 Participants |
| Placebo | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | TE ADA Inconclusive | 1 Participants |
| ALX-0171 3.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Total TE ADA Negative | 17 Participants |
| ALX-0171 3.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | TE ADA Equivocal | 12 Participants |
| ALX-0171 3.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | TE ADA Inconclusive | 1 Participants |
| ALX-0171 3.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Total TE ADA Positive | 15 Participants |
| ALX-0171 6.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | TE ADA Equivocal | 13 Participants |
| ALX-0171 6.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Total TE ADA Negative | 14 Participants |
| ALX-0171 6.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | TE ADA Inconclusive | 1 Participants |
| ALX-0171 6.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Total TE ADA Positive | 16 Participants |
| ALX-0171 9.0mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | TE ADA Inconclusive | 4 Participants |
| ALX-0171 9.0mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Total TE ADA Negative | 13 Participants |
| ALX-0171 9.0mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | Total TE ADA Positive | 15 Participants |
| ALX-0171 9.0mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Anti-drug Antibodies | TE ADA Equivocal | 14 Participants |
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.
Time frame: Overall Study Period (i.e., approximately 28 days)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Positive | 2 Participants |
| Placebo | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Missing | 1 Participants |
| Placebo | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Negative | 36 Participants |
| ALX-0171 3.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Positive | 11 Participants |
| ALX-0171 3.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Missing | 1 Participants |
| ALX-0171 3.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Negative | 33 Participants |
| ALX-0171 6.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Negative | 26 Participants |
| ALX-0171 6.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Positive | 18 Participants |
| ALX-0171 6.0 mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Missing | 0 Participants |
| ALX-0171 9.0mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Positive | 12 Participants |
| ALX-0171 9.0mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Missing | 3 Participants |
| ALX-0171 9.0mg/kg | Immunogenicity; Number of Subjects With Treatment-emergent Neutralizing Antibodies | Post-dose Negative | 31 Participants |
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.
Time frame: Overall Study Period (i.e., approximately 28 days)
Population: 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).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time-to-BQL (RT-qPCR) | 26.7 hours |
| ALX-0171 3.0 mg/kg | Time-to-BQL (RT-qPCR) | 26.8 hours |
| ALX-0171 6.0 mg/kg | Time-to-BQL (RT-qPCR) | 28.9 hours |
| ALX-0171 9.0mg/kg | Time-to-BQL (RT-qPCR) | 6.3 hours |
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).
Time frame: Overall Study Period (i.e., approximately 28 days)
Population: 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).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time-to-Clinical Response | Time-to-Clinical Response | 47.9 hours |
| Placebo | Time-to-Clinical Response | Time-to-adequate oxygen saturation | 53.4 hours |
| Placebo | Time-to-Clinical Response | Time-to-adequate oral feeding | 43.7 hours |
| ALX-0171 3.0 mg/kg | Time-to-Clinical Response | Time-to-Clinical Response | 44.1 hours |
| ALX-0171 3.0 mg/kg | Time-to-Clinical Response | Time-to-adequate oxygen saturation | 38.5 hours |
| ALX-0171 3.0 mg/kg | Time-to-Clinical Response | Time-to-adequate oral feeding | 44.0 hours |
| ALX-0171 6.0 mg/kg | Time-to-Clinical Response | Time-to-adequate oral feeding | 17.6 hours |
| ALX-0171 6.0 mg/kg | Time-to-Clinical Response | Time-to-Clinical Response | 27.9 hours |
| ALX-0171 6.0 mg/kg | Time-to-Clinical Response | Time-to-adequate oxygen saturation | 29.5 hours |
| ALX-0171 9.0mg/kg | Time-to-Clinical Response | Time-to-Clinical Response | 46.3 hours |
| ALX-0171 9.0mg/kg | Time-to-Clinical Response | Time-to-adequate oxygen saturation | 46.5 hours |
| ALX-0171 9.0mg/kg | Time-to-Clinical Response | Time-to-adequate oral feeding | 23.8 hours |
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.
Time frame: Overall Study Period (i.e., approximately 28 days)
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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time-to-undetectable Viral Load (Plaque Assay Analysis) | 95.9 hours |
| ALX-0171 3.0 mg/kg | Time-to-undetectable Viral Load (Plaque Assay Analysis) | 26.3 hours |
| ALX-0171 6.0 mg/kg | Time-to-undetectable Viral Load (Plaque Assay Analysis) | 21.0 hours |
| ALX-0171 9.0mg/kg | Time-to-undetectable Viral Load (Plaque Assay Analysis) | 5.1 hours |
Secondary
Viral Load Changes From Baseline (Plaque Assay Analysis)
Change from Baseline in RSV Load measured by Plaque Assay (RSV Infected Population)
Time frame: From Baseline until Day 14 (Follow-up) (Baseline; Day 1, 5 hours post-dose; Day 3, 2 hours post-dose; and Follow-up reported)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Viral Load Changes From Baseline (Plaque Assay Analysis) | Baseline | 3.494 log10 pfu/mL | Standard Error 0.2396 |
| Placebo | Viral Load Changes From Baseline (Plaque Assay Analysis) | Day 1, 5 hours post-dose | -0.270 log10 pfu/mL | Standard Error 0.1607 |
| Placebo | Viral Load Changes From Baseline (Plaque Assay Analysis) | Day 3, 2 hours post-dose | -1.936 log10 pfu/mL | Standard Error 0.2317 |
| Placebo | Viral Load Changes From Baseline (Plaque Assay Analysis) | Follow-up | -2.368 log10 pfu/mL | Standard Error 0.2946 |
| ALX-0171 3.0 mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Day 1, 5 hours post-dose | -2.173 log10 pfu/mL | Standard Error 0.2123 |
| ALX-0171 3.0 mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Day 3, 2 hours post-dose | -2.396 log10 pfu/mL | Standard Error 0.2234 |
| ALX-0171 3.0 mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Follow-up | -2.431 log10 pfu/mL | Standard Error 0.2202 |
| ALX-0171 3.0 mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Baseline | 3.312 log10 pfu/mL | Standard Error 0.2165 |
| ALX-0171 6.0 mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Day 3, 2 hours post-dose | -2.134 log10 pfu/mL | Standard Error 0.2525 |
| ALX-0171 6.0 mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Day 1, 5 hours post-dose | -2.189 log10 pfu/mL | Standard Error 0.2676 |
| ALX-0171 6.0 mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Follow-up | -2.279 log10 pfu/mL | Standard Error 0.2576 |
| ALX-0171 6.0 mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Baseline | 3.135 log10 pfu/mL | Standard Error 0.243 |
| ALX-0171 9.0mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Follow-up | -1.416 log10 pfu/mL | Standard Error 0.2821 |
| ALX-0171 9.0mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Day 1, 5 hours post-dose | -1.535 log10 pfu/mL | Standard Error 0.2526 |
| ALX-0171 9.0mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Baseline | 2.385 log10 pfu/mL | Standard Error 0.2526 |
| ALX-0171 9.0mg/kg | Viral Load Changes From Baseline (Plaque Assay Analysis) | Day 3, 2 hours post-dose | -1.516 log10 pfu/mL | Standard Error 0.2558 |
Secondary
Viral Load Changes From Baseline (RT-qPCR Analysis)
Change from Baseline in RSV Load measured by RT-qPCR (RSV Infected Population)
Time frame: From Baseline until Day 14 (Follow-up) (Baseline; Day 1, 5 hours post-dose; Day 3, 2 hours post-dose; and Follow-up reported)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Viral Load Changes From Baseline (RT-qPCR Analysis) | Baseline | 5.236 log10 copies/mL | Standard Error 0.2827 |
| Placebo | Viral Load Changes From Baseline (RT-qPCR Analysis) | Day 1, 5 hours post-dose | -0.221 log10 copies/mL | Standard Error 0.1601 |
| Placebo | Viral Load Changes From Baseline (RT-qPCR Analysis) | Day 3, 2 hours post-dose | -2.156 log10 copies/mL | Standard Error 0.2454 |
| Placebo | Viral Load Changes From Baseline (RT-qPCR Analysis) | Follow-up | -3.413 log10 copies/mL | Standard Error 0.3715 |
| ALX-0171 3.0 mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Day 1, 5 hours post-dose | -0.544 log10 copies/mL | Standard Error 0.1286 |
| ALX-0171 3.0 mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Day 3, 2 hours post-dose | -2.589 log10 copies/mL | Standard Error 0.2138 |
| ALX-0171 3.0 mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Follow-up | -3.665 log10 copies/mL | Standard Error 0.2203 |
| ALX-0171 3.0 mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Baseline | 4.966 log10 copies/mL | Standard Error 0.2095 |
| ALX-0171 6.0 mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Day 3, 2 hours post-dose | -2.310 log10 copies/mL | Standard Error 0.2797 |
| ALX-0171 6.0 mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Day 1, 5 hours post-dose | -0.241 log10 copies/mL | Standard Error 0.2031 |
| ALX-0171 6.0 mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Follow-up | -3.972 log10 copies/mL | Standard Error 0.2032 |
| ALX-0171 6.0 mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Baseline | 5.232 log10 copies/mL | Standard Error 0.1899 |
| ALX-0171 9.0mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Follow-up | -3.033 log10 copies/mL | Standard Error 0.3252 |
| ALX-0171 9.0mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Day 1, 5 hours post-dose | -0.449 log10 copies/mL | Standard Error 0.1883 |
| ALX-0171 9.0mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Baseline | 4.525 log10 copies/mL | Standard Error 0.2937 |
| ALX-0171 9.0mg/kg | Viral Load Changes From Baseline (RT-qPCR Analysis) | Day 3, 2 hours post-dose | -2.025 log10 copies/mL | Standard Error 0.284 |
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\<x), the endpoint was defined as (AUCt - t\*viral load at baseline) / t.
Time frame: From Baseline until Day 14 (Follow-up) (Baseline, Day 3, and Follow-up reported)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Baseline | 3.494 log10 pfu/mL | Standard Error 0.2396 |
| Placebo | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Follow-Up | -2.096 log10 pfu/mL | Standard Error 0.2443 |
| Placebo | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Day 3 | -1.014 log10 pfu/mL | Standard Error 0.154 |
| ALX-0171 3.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Baseline | 3.312 log10 pfu/mL | Standard Error 0.2165 |
| ALX-0171 3.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Follow-Up | -2.295 log10 pfu/mL | Standard Error 0.2116 |
| ALX-0171 3.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Day 3 | -1.924 log10 pfu/mL | Standard Error 0.1659 |
| ALX-0171 6.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Day 3 | -1.804 log10 pfu/mL | Standard Error 0.2098 |
| ALX-0171 6.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Baseline | 3.135 log10 pfu/mL | Standard Error 0.243 |
| ALX-0171 6.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Follow-Up | -2.028 log10 pfu/mL | Standard Error 0.2217 |
| ALX-0171 9.0mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Baseline | 2.385 log10 pfu/mL | Standard Error 0.2526 |
| ALX-0171 9.0mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Follow-Up | -1.419 log10 pfu/mL | Standard Error 0.2488 |
| ALX-0171 9.0mg/kg | Viral Load Time-weighted Average Changes From Baseline (Plaque Assay Analysis) | Day 3 | -1.330 log10 pfu/mL | Standard Error 0.2434 |
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\<x), the endpoint was defined as (AUCt - t\*viral load at baseline) / t.
Time frame: From Baseline until Day 14 (Follow-up) (Baseline, Day 3, and Follow-up reported)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Baseline | 5.236 log10 copies/mL | Standard Error 0.2827 |
| Placebo | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Follow-up | -2.684 log10 copies/mL | Standard Error 0.2263 |
| Placebo | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Day 3 | -0.933 log10 copies/mL | Standard Error 0.1421 |
| ALX-0171 3.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Baseline | 4.966 log10 copies/mL | Standard Error 0.2095 |
| ALX-0171 3.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Follow-up | -2.828 log10 copies/mL | Standard Error 0.2099 |
| ALX-0171 3.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Day 3 | -1.209 log10 copies/mL | Standard Error 0.1301 |
| ALX-0171 6.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Day 3 | -1.113 log10 copies/mL | Standard Error 0.1932 |
| ALX-0171 6.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Baseline | 5.232 log10 copies/mL | Standard Error 0.1899 |
| ALX-0171 6.0 mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Follow-up | -2.756 log10 copies/mL | Standard Error 0.1831 |
| ALX-0171 9.0mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Baseline | 4.525 log10 copies/mL | Standard Error 0.2937 |
| ALX-0171 9.0mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Follow-up | -2.292 log10 copies/mL | Standard Error 0.2581 |
| ALX-0171 9.0mg/kg | Viral Load Time-weighted Average Changes From Baseline (RT-qPCR Analysis) | Day 3 | -0.842 log10 copies/mL | Standard Error 0.1842 |