Evaluation of ALX-0171 in Japanese Children Hospitalized for Respiratory Syncytial Virus Lower Respiratory Tract Infection

NCT03418571 | Terminated Phase 2 Results DMC

• 1 other identifier: ALX0171-C203
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 25

Brief Summary

This was a randomized, double-blind, multicenter, Phase II study (NCT03418571) designed to support the selection of an optimal dose of inhaled ALX-0171 for further clinical development, taking ethnicity into consideration. Based on the results of the Phase IIb dose-ranging study ALX0171-C201 (RESPIRE), the Sponsor decided to discontinue ALX-0171 development in infants and to early terminate the ALX0171-C203 study.

Conditions

Respiratory Syncytial Virus Lower Respiratory Tract Infection

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability of Inhaled ALX-0171 1.5 mg/kg as Measured by the Number of Subjects With at Least 1 Serious or Non-Serious Treatment-emergent Adverse Event (TEAE).

  Number of subjects reported with at least 1 serious or non-serious TEAEs in the ALX-0171 1.5 mg/kg treatment group and placebo treatment group.

  From the subject's first study drug administration until completion of the subject's last visit, an average of 4 weeks

• Safety and Tolerability of Inhaled ALX-0171 1.5 mg/kg as Measured by the Number of Serious and Non-serious TEAEs.

  Number of serious and non-serious TEAEs reported in the ALX-0171 1.5 mg/kg treatment group and placebo treatment group.

  From the subject's first study drug administration until completion of the subject's last visit, an average of 4 weeks

Study Arms (2)

ALX-0171 1.5 mg/kg

EXPERIMENTAL

Biological: ALX-0171 1.5 mg/kg

Placebo

PLACEBO COMPARATOR

Other: Placebo

Interventions

ALX-0171 1.5 mg/kg BIOLOGICAL

ALX-0171 1.5 mg/kg was administered via a single inhalation once daily for 3 consecutive days.

ALX-0171 1.5 mg/kg

Placebo OTHER

Placebo was administered via a single inhalation once daily for 3 consecutive days.

Placebo

Eligibility Criteria

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

You may qualify if:

• Subject was a Japanese male or female infant or young child aged 28 days to \<2 years with gestational age ≥33 weeks at screening.
• Subject was of Japanese descent, i.e., born in Japan to Japanese parents and had Japanese maternal and paternal grandparents.
• Subject weighed between ≥3.0 kg and \<15.0 kg at screening.
• Subject was 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 within 4 days of 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 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 two of the following RSV disease severity criteria at screening and randomization:
• Inadequate oral feeding that required feeding support (i.e., nasogastric tube or i.v. line),
• Inadequate oxygen saturation defined as:
• Peripheral capillary oxygen saturation (SpO2) \<95% on room air, or
• Requiring oxygen supplementation to maintain adequate oxygen saturation with documented pre-supplementation value \<95%
• Signs of respiratory distress defined as:
• Respiratory rate ≥50 breaths per minute in infants up to 12 months of age, and ≥40 breaths per minute in children above 12 months, and/ or
• Moderate or marked respiratory muscle retractions

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 which would have prevented 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 current admission, subject was initially hospitalized in an Intensive Care Unit (ICU) setting and/or 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/minute could be provided through the nebulizer)
• Subject had received 1 or more doses of palivizumab or treatment or prophylaxis with any RSV antiviral compound (e.g., ribavirin, i.v. immunoglobulin, or any investigational drug or vaccine for RSV \[including subject's mother who had been vaccinated against RSV\]) at any time prior to screening.
• Subject was required to continue or start systemic corticosteroid therapy. Subject on a maintenance therapy of inhaled corticosteroids could continue this treatment at the usual dose. Topical corticosteroids for skin disorders were permitted.

Sponsors & Collaborators

• Ablynx, a Sanofi company: lead

Study Sites (25)

Investigator Site

Aoi-ku, Japan

Location

Investigator Site

Asahikawa, Japan

Location

Investigator Site

Fuchu-shi, Japan

Location

Investigator site

Fukuyama-shi, Japan

Location

Investigator Site

Funabashi, Japan

Location

Investigator site

Gifu, Japan

Location

Investigator Site

Isesaki, Japan

Location

Investigator Site

Kawasaki, Japan

Location

Investigator Site

Koga, Japan

Location

Investigator Site

Kurashiki, Japan

Location

Investigator Site

Kurume-shi, Japan

Location

Investigator Site

Meguro-ku, Japan

Location

Investigator Site

Minamiku, Japan

Location

Investigator site

Nagano, Japan

Location

Investigator Site

Ōmura, Japan

Location

Investigator site

Saitama-shi, Japan

Location

Investigator Site

Shimotsuke-shi, Japan

Location

Investigator Site

Takatsuki, Japan

Location

Investigator Site

Toshima-ku, Japan

Location

Investigator Site

Toyohira, Japan

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Investigator site

Ueda, Japan

Location

Investigator site

Wako, Japan

Location

Investigator Site

Yachiyo, Japan

Location

Investigator site 1

Yokosuka, Japan

Location

Investigator site 2

Yokosuka, Japan

Location

MeSH Terms

Interventions

gontivimab

Limitations and Caveats

Based on the results of the Phase IIb study ALX0171-C201 (RESPIRE), the Sponsor decided to discontinue ALX-0171 development in infants and to early terminate the ALX0171-C203 study. Therefore, no data are available for the higher dose groups.

Results Point of Contact

• Title: Medical Monitor
• Organization: Ablynx NV

clinicaltrials@ablynx.com

+32 9 262 00 00

Study Officials

• Medical Monitor

  Ablynx NV

  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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2018
• First Posted: February 1, 2018
• Study Start: March 1, 2018
• Primary Completion: October 24, 2018
• Study Completion: October 24, 2018
• Last Updated: July 30, 2019
• Results First Posted: July 15, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (25)