Study of the Efficacy and Safety of MEDI4893

NCT02296320 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CD-ID-MEDI4893-1139
• Study Type: interventional
• Target: 213
• Locations: 10 countries
• Sites: 49

Brief Summary

Clinical trial looking at safety and efficacy of MEDI4893 in prevention of pneumonia caused by Staphylococcus aureus in high-risk patients

Conditions

Staphylococcus Aureus Pneumonia

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants With Endpoint Adjudication Committee-Determined (EAC) Staphylococcus Aureus (S Aureus) Pneumonia

  The EAC S aureus pneumonia was based on clinical, radiographic, and microbiologic criteria. Clinical criteria: 1 major criteria (PaO2/FiO2 ratio \< 240 mmHg maintained for at least 4 hours or decrease in PaO2/FiO2 by \>= 50 mmHg maintained for at least 4 hrs or a need to initiate non-invasive mechanical ventilation or re-initiate invasive mechanical ventilation because of respiratory failure or worsening of respiratory status); and at least 2 of minor criteria (systemic signs of infection, production of purulent sputum/endotracheal secretions, new onset of cough, physical examination findings consistent with pneumonia/pulmonary consolidation, dyspnea, and/or tachypnea). Radiographic criteria: new or worsening infiltrate consistent with pneumonia on chest X-ray obtained within 24 hrs of event. Microbiologic criteria: at least 1 culture positive for S aureus (respiratory specimen, or blood, or pleural fluid aspirate or lung tissue culture during episode of pneumonia).

  Day 1 through Day 31

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) Through 31 Days

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  Day 1 through Day 31

• Number of Participants With TEAEs Through 91 Days

  An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  Day 1 through Day 91

• Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs)

  A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  Day 1 through Day 191

• Number of Participants With Adverse Events of Special Interest (AESIs)

  An AESI is one of scientific and medical interest specific to understanding of the study drug and may have required close monitoring and rapid communication by the investigator to the sponsor. An AESI may have been serious or non-serious.

  Day 1 through Day 191

• Number of Participants With New Onset Chronic Diseases (NOCDs)

  An NOCD defined as a newly diagnosed medical condition that is of a chronic, ongoing nature. It is observed after receiving the study drug and is assessed by the investigator as medically significant.

  Day 1 through Day 191

Secondary Outcomes (5)

• Maximum Observed Serum Concentration (Cmax) of MEDI4893

  Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 91

• Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) of MEDI4893

  Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 91

• Observed Serum Concentration of MEDI4893 Through 30 Days Post Dose (C30)

  Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, and 30

• Observed Serum Concentration of MEDI4893 Through 90 Days Post Dose (C90)

  Day 1 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 4, 8, 15, 22, 31, 61, and 90

• Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to MEDI4893

  Pre-dose on Day 1 (Baseline); and on Days 31, 61, and 91

Study Arms (3)

MEDI4893 5000 mg

ACTIVE COMPARATOR

Participants will receive a single intravenous (IV) dose of MEDI4893 5000 milligrams (mg) on Day 1 of the study.

Drug: MEDI4893

Placebo

PLACEBO COMPARATOR

Participants will receive a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.

Other: Placebo

MEDI4893 2000 mg

ACTIVE COMPARATOR

Participants will receive a single IV dose of MEDI4893 2000 mg on Day 1 of the study.

Drug: MEDI4893

Interventions

MEDI4893 DRUG

Participants will receive a single IV dose of MEDI4893 2000 or 5000 mg on Day 1 of the study.

MEDI4893 2000 mg; MEDI4893 5000 mg

Placebo OTHER

Participants will receive a single IV dose of placebo matched to MEDI4893 on Day 1 of the study.

Placebo

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Colonized with Staphylococcus aureus, expected to require prolonged intubation and mechanical ventilation, without any evidence of active pneumonia.

You may not qualify if:

• Staphylococcal disease at randomisation; lung injury score consistent with pneumonia; current lung disease; chronic tracheostomy patients; currently receiving systemic anti-staphylococcal antibiotics; moribund patients.

Sponsors & Collaborators

• MedImmune LLC: lead
• Innovative Medicines Initiative: collaborator
• Antibacterial Resistance Leadership Group: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (49)

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Detroit, Michigan, 48202, United States

Location

Research Site

Arlon, 6700, Belgium

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Brussels, Belgium

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La Louvière, 7100, Belgium

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Lodelinsart, 6042, Belgium

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Yvoir, 5530, Belgium

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Brno, 656 91, Czechia

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Děčín, 405 99, Czechia

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Kyjov, 697 01, Czechia

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Prague, 128 08, Czechia

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Teplice, 415 29, Czechia

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Angers, 49933, France

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Clermont-Ferrand, 63003, France

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Garches, 92380, France

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Grenoble, 38043, France

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Le Chesnay, 78157, France

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Lille, 59037, France

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Limoges, 87042, France

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Lyon, 69394, France

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Nantes, 44093, France

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Orléans, 45100, France

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Pierre-Bénite, 69495, France

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Poitiers, 86201, France

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Rennes, 35033, France

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Tours, 37044, France

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Berlin, 12351, Germany

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Berlin, 13353, Germany

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Erfurt, 99089, Germany

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Heidelberg, 69120, Germany

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Jena, 07740, Germany

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Alexandroupoli, 68100, Greece

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Athens, 14564, Greece

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Ioannina, 455 00, Greece

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Larissa, 41110, Greece

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Larissa, 41221, Greece

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Kistarcsa, 02143, Hungary

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Vác, 2600, Hungary

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Ponte de Lima, 4990-041, Portugal

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Getafe, 28905, Spain

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Madrid, 28040, Spain

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Oviedo, 33011, Spain

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Terrassa, 08221, Spain

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Valencia, 46014, Spain

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Valencia, 46026, Spain

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Geneva, 1211, Switzerland

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Lausanne, CH-1011, Switzerland

Location

Related Publications (2)

• Francois B, Jafri HS, Chastre J, Sanchez-Garcia M, Eggimann P, Dequin PF, Huberlant V, Vina Soria L, Boulain T, Bretonniere C, Pugin J, Trenado J, Hernandez Padilla AC, Ali O, Shoemaker K, Ren P, Coenjaerts FE, Ruzin A, Barraud O, Timbermont L, Lammens C, Pierre V, Wu Y, Vignaud J, Colbert S, Bellamy T, Esser MT, Dubovsky F, Bonten MJ, Goossens H, Laterre PF; COMBACTE Consortium and the SAATELLITE Study Group. Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial. Lancet Infect Dis. 2021 Sep;21(9):1313-1323. doi: 10.1016/S1473-3099(20)30995-6. Epub 2021 Apr 21.

  PMID: 33894131 DERIVED

• Yu XQ, Robbie GJ, Wu Y, Esser MT, Jensen K, Schwartz HI, Bellamy T, Hernandez-Illas M, Jafri HS. Safety, Tolerability, and Pharmacokinetics of MEDI4893, an Investigational, Extended-Half-Life, Anti-Staphylococcus aureus Alpha-Toxin Human Monoclonal Antibody, in Healthy Adults. Antimicrob Agents Chemother. 2016 Dec 27;61(1):e01020-16. doi: 10.1128/AAC.01020-16. Print 2017 Jan.

  PMID: 27795368 DERIVED

Related Links

• CD-ID-MEDI4893-1139 Protocol amendment 5\_redacted\_FINAL\_APPROVED
• CD-ID-MEDI4893-1139 Statistical Analysis Plan\_Final v4.0\_Redacted\_FINAL\_APPROVED

MeSH Terms

Conditions

Pneumonia, Staphylococcal

Interventions

suvratoxumab

Condition Hierarchy (Ancestors)

Staphylococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia, Bacterial; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Hasan S. Jafri
• Organization: MedImmune, LLC

information.center@astrazeneca.com

301-398-4431

Study Officials

• MedImmune LLC

  MedImmune LLC

  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: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2014
• First Posted: November 20, 2014
• Study Start: October 10, 2014
• Primary Completion: October 2, 2018
• Study Completion: October 2, 2018
• Last Updated: December 23, 2019
• Results First Posted: October 25, 2019

Record last verified: 2019-12

Locations

DE (5); PT (1); GR (5); US (2); HU (2); BE (5); ES (8); CH (2); CZ (5); FR (14)