Dose Ranging Study of ALX-0171 in Infants Hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection

NCT02979431 | Completed Phase 2 Results DMC

• 2 other identifiers: ALX0171-C2012016-001651-49
• Study Type: interventional
• Target: 180
• Locations: 16 countries
• Sites: 63

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.

Conditions

Respiratory Syncytial Virus Lower Respiratory Tract Infection

Keywords

RSV, Lower Respiratory Tract Infection, pediattric patients

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (10)

• Change From Baseline in Global Severity Score on Day 2 (5 Hours Post-dose)

  from Baseline untill Day 2 (5 hours post-dose)

• Time-to-Clinical Response

  Overall Study Period (i.e., approximately 28 days)

• Time-to-BQL (RT-qPCR)

  Overall Study Period (i.e., approximately 28 days)

• Time-to-undetectable Viral Load (Plaque Assay Analysis)

  Overall Study Period (i.e., approximately 28 days)

• 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)

Study Arms (4)

ALX-0171 3.0 mg/kg

EXPERIMENTAL

Inhalation of ALX-0171 3.0 mg/kg once daily for 3 consecutive days

Biological: ALX-0171 3.0 mg/kg

ALX-0171 6.0 mg/kg

EXPERIMENTAL

Inhalation of ALX-0171 6.0 mg/kg once daily for 3 consecutive days

Biological: ALX-0171 6.0 mg/kg

ALX-0171 Dose 9.0mg/kg

EXPERIMENTAL

Inhalation of ALX-0171 9.0 mg/kg once daily for 3 consecutive days

Biological: ALX-0171 9.0 mg/kg

Placebo

PLACEBO COMPARATOR

Inhalation of Placebo once daily for 3 consecutive days

Other: Placebo

Interventions

ALX-0171 3.0 mg/kg BIOLOGICAL

ALX-0171 3.0 mg/kg

ALX-0171 6.0 mg/kg BIOLOGICAL

ALX-0171 6.0 mg/kg

ALX-0171 9.0 mg/kg BIOLOGICAL

ALX-0171 Dose 9.0mg/kg

Placebo OTHER

Also known as: Matching Placebo

Placebo

Eligibility Criteria

• Age: 28 Days - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• 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
• Normal psychomotor development.

You may not qualify if:

• 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.
• Subject was known to be immunocompromised.
• 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:
• 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)

Sponsors & Collaborators

• Ablynx, a Sanofi company: lead

Study Sites (74)

Investigator site 2

Brussels, Belgium

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Brussels, Belgium

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Edegem, Belgium

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Leuven, Belgium

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Roeselare, Belgium

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Kozloduy, Bulgaria

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Plovdiv, Bulgaria

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Rousse, Bulgaria

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Sofia, Bulgaria

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Stara Zagora, Bulgaria

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Santiago, Chile

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Valdivia, Chile

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Cali, Colombia

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Floridablanca, Colombia

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Medellín, Colombia

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Medellín, Colombia

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Čakovec, Croatia

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Osijek, Croatia

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Slavonski Brod, Croatia

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Varaždin, Croatia

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Zagreb, Croatia

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Zagreb, Croatia

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Zagreb, Croatia

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Zagreb, Croatia

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Hradec Králové, Czechia

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Tartu, Estonia

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Bochum, Germany

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Dresden, Germany

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Sankt Augustin, Germany

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Wuppertal, Germany

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Balassagyarmat, Hungary

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Budapest, Hungary

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Budapest, Hungary

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Budapest, Hungary

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Budapest, Hungary

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Debrecen, Hungary

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Szeged, Hungary

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Székesfehérvár, Hungary

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Veszprém, Hungary

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Beersheba, Israel

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Haifa, Israel

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Petah Tikva, Israel

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Daugavpils, Latvia

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Riga, Latvia

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George Town, Malaysia

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Kuala Lumpur, Malaysia

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Seremban, Malaysia

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Sibu, Malaysia

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Alabang, Philippines

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Manila, Philippines

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Quezon City, Philippines

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Quezon City, Philippines

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Lublin, Poland

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Trzebnica, Poland

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Banská Bystrica, Slovakia

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Bratislava, Slovakia

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Košice, Slovakia

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Poprad, Slovakia

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Barcelona, Spain

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Barcelona, Spain

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Barcelona, Spain

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Bilbao, Spain

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El Palmar, Spain

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Madrid, Spain

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Madrid, Spain

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Málaga, Spain

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Santiago de Compostela, Spain

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Seville, Spain

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Valencia, Spain

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Bangkok, Thailand

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Bangkok, Thailand

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Chiang Mai, Thailand

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Hat Yai, Thailand

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Khon Kaen, Thailand

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MeSH Terms

Interventions

gontivimab

Results Point of Contact

• Title: Medical Monitor
• Organization: Ablynx NV

clinicaltrials@ablynx.com

+32 (0)9262 00 00

Study Officials

• Ablynx Clinical Department

  Ablynx, a Sanofi company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 1, 2016
• Study Start: January 11, 2017
• Primary Completion: May 25, 2018
• Study Completion: May 25, 2018
• Last Updated: October 18, 2019
• Results First Posted: October 18, 2019

Record last verified: 2019-09

Locations

ES (1); CO (4); PL (2); HU (9); BU (5); CR (8); DE (4); PH (4); CZ (1); SL (4); BE (5); MY (4); CL (2); LA (2); TH (5); IL (3)