Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus Infection of the Upper Respiratory Tract

NCT02254408 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-218-01082014-002474-36
• Study Type: interventional
• Target: 189
• Locations: 15 countries
• Sites: 68

Brief Summary

The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV upper respiratory tract infection (URTI), the effect of presatovir on development of lower respiratory tract complication, being free of any supplemental oxygen progression to respiratory failure, and pharmacokinetics (PK), safety, and tolerability of presatovir.

Conditions

Respiratory Syncytial Virus

Keywords

Respiratory Syncytial Virus (RSV); Antiviral; Hematopoietic Cell Transplant (HCT); Upper respiratory tract infection

Outcome Measures

Primary Outcomes (2)

• Time-Weighted Average Change in Nasal Respiratory Syncytial Virus (RSV ) Viral Load From Baseline (Day 1) to Day 9

  The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.

  Baseline; Day 9

• Percentage of Participants Who Developed a Lower Respiratory Tract Complication

  A Lower Respiratory Tract Complication (LRTC) was defined as one of the below as determined by the adjudication committee: * Primary RSV lower respiratory tract infection (LRTI) * Secondary bacterial LRTI * LRTI due to unusual pathogens * Lower respiratory tract complication of unknown etiology

  Up to Day 28

Secondary Outcomes (1)

• Percentage of Participants Who Developed Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality

  Up to Day 28

Study Arms (2)

Presatovir

EXPERIMENTAL

Participants will receive presatovir on Days 1, 5, 9, 13, and 17, with follow-up visits through Day 28, and may continue in an optional extended monitoring phase with visits through Day 56.

Drug: Presatovir

Placebo

PLACEBO COMPARATOR

Participants will receive placebo on Days 1, 5, 9, 13, and 17, with follow-up visits through Day 28, and may continue in an optional extended monitoring phase with visits through Day 56.

Drug: Placebo

Interventions

Presatovir DRUG

Presatovir 200 mg (4 × 50 mg tablets) administered orally or via nasogastric (NG) tube

Also known as: GS-5806

Presatovir

Placebo DRUG

Tablets administered orally or via nasogastric tube

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Received an autologous or allogeneic HCT using any conditioning regimen
• Documented to be RSV-positive as determined by local testing (eg, polymerase chain reaction, direct fluorescence antibody, respiratory viral panel assay, or culture) using an upper respiratory tract sample collected ≤ 6 days prior to Day 1
• New onset of at least 1 of the following respiratory symptoms for ≤ 7 days prior to Day 1: nasal congestion, runny nose, cough, or sore throat, or worsening of one of these chronic (associated with a previously existing diagnosis, eg, chronic rhinorrhea, seasonal allergies, chronic lung disease) respiratory symptoms ≤ 7 days prior to Day 1
• No evidence of new abnormalities consistent with lower respiratory tract infection (LRTI) on a chest X-ray relative to the most recent chest X-ray, as determined by the local radiologist. If a chest X-ray is not available or was not obtained during standard care \< 48 hours prior to screening, a chest X-ray must be obtained for screening
• O2 saturation ≥ 92% on room air
• An informed consent document signed and dated by the participant or a legal guardian of the participant and the investigator or his/her designee
• A negative urine or serum pregnancy test is required for female participants (unless surgically sterile or greater than two years post-menopausal)
• Male and female participants of childbearing potential must agree to contraceptive requirements as described in the study protocol
• Willingness to complete necessary study procedures and have available a working telephone or email

You may not qualify if:

• Related to concomitant or previous medication use:
• Use of non-marketed (according to region) investigational agents within 30 days, OR use of any monoclonal anti-RSV antibodies within 4 months or 5 half-lives of screening, whichever is longer, OR use of any investigational RSV vaccines after HCT
• Related to medical history:
• Pregnant, breastfeeding, or lactating females
• Unable to tolerate nasal sampling required for this study, as determined by the investigator
• Known history of HIV/AIDS with a CD4 count \<200 cells/μL within the last month
• History of drug and/or alcohol abuse that, in the opinion of the investigator, may prevent adherence to study activities
• Related to medical condition at screening:
• Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, or human metapneumovirus, or coronavirus) within 7 days prior to the screening visit, as determined by local testing (additional testing is not required)
• Clinically significant bacteremia or fungemia within 7 days prior to screening that has not been adequately treated, as determined by the investigator
• Clinically significant bacterial, fungal, or viral pneumonia within 2 weeks prior to screening that has not been adequately treated, as determined by the investigator
• Excessive nausea/vomiting at screening, as determined by the investigator, or an inability to swallow pills that precludes oral administration of the investigational medical product (for participants without an nasogastric tube in place)
• Any condition which, in the opinion of the investigator, would prevent full participation in this trial or would interfere with the evaluation of the trial endpoints
• Related to laboratory results:
• Creatinine clearance \< 30 mL/min (calculated using the Cockcroft-Gault method)

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (68)

Mayo Clinic Arizona

Phoenix, Arizona, United States

Location

City of Hope

Duarte, California, United States

Location

UCLA David Geffen School of Medicine

Los Angeles, California, United States

Location

Stanford University

Stanford, California, United States

Location

Emory University

Atlanta, Georgia, United States

Location

NorthSide Medical Center

Atlanta, Georgia, United States

Location

Northwestern University

Chicago, Illinois, United States

Location

University of Chicago

Chicago, Illinois, United States

Location

Loyola University

Maywood, Illinois, United States

Location

John Hopkins

Baltimore, Maryland, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Location

University of Massachusetts Memorial Cancer Center

Boston, Massachusetts, United States

Location

University of Michigan

Ann Arbor, Michigan, United States

Location

Wayne State University

Detroit, Michigan, United States

Location

University of Minnesota

Minneapolis, Minnesota, United States

Location

Washington University

St Louis, Missouri, United States

Location

Memorial Sloan Kettering

New York, New York, United States

Location

New York Presbyterian Hospital Cornell Medical Center

New York, New York, United States

Location

Duke University

Durham, North Carolina, United States

Location

University Hospital Case Medical

Cleveland, Ohio, United States

Location

Oregon Health Sciences University

Portland, Oregon, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Location

MD Anderson Cancer Center

Houston, Texas, United States

Location

Texas Transplant Institute (SCRI)

San Antonio, Texas, United States

Location

University of Utah

Salt Lake City, Utah, United States

Location

Fred Hutchison Cancer Research Center

Seattle, Washington, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Location

Westmead Hospital

Westmead, New South Wales, Australia

Location

Royal Brisbane & Women's Hospital

Herston, Australia

Location

Royal Melbourne Hospital

Melbourne, Australia

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, Brazil

Location

Fundacao Faculdade Regional Medicina de Sao Jose do Rio Preto

São Paulo, Brazil

Location

Fundação Antonio Prudente - Hospital do Câncer AC Camargo

São Paulo, Brazil

Location

Hospital Israelita Albert Einstein

São Paulo, Brazil

Location

Hospital Santa Marcelina

São Paulo, Brazil

Location

Hospital Universitario USP

São Paulo, Brazil

Location

Instituto Brasileiro de Controle do Câncer-IBCC

São Paulo, Brazil

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Location

Tom Baker Cancer Centre

Calgary, Canada

Location

CHU de Bordeaux

Bordeaux, France

Location

Hopital Saint-Louis, APHP

Paris, France

Location

Hopital Foch

Suresnes, France

Location

Institut Universitaire du Cancer Oncopole

Toulouse, France

Location

Universitatsklinikum Wurzburg

Würzburg, Germany

Location

Soroka Medical Center

Beersheba, Israel

Location

Rambam Medical Center

Haifa, Israel

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

VUmc cancer center

Amsterdam, Netherlands

Location

Erasmus Medical Center (Rotterdam)

Rotterdam, Netherlands

Location

Singapore General Hospital

Singapore, Singapore

Location

UMC National University Health System

Singapore, Singapore

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Seoul Saint Mary's Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Hospital universitario Virgen del Rocio

Seville, Spain

Location

Karolinska Institutet

Stockholm, Sweden

Location

University Clinic Basel

Basel, Switzerland

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Chang Gung Medical Foundation-LinKou Branch

Taoyuan District, Taiwan

Location

Leeds Teaching Hospitals Trust

Leeds, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

Related Publications (1)

• Chemaly RF, Dadwal SS, Bergeron A, Ljungman P, Kim YJ, Cheng GS, Pipavath SN, Limaye AP, Blanchard E, Winston DJ, Stiff PJ, Zuckerman T, Lachance S, Rahav G, Small CB, Mullane KM, Patron RL, Lee DG, Hirsch HH, Waghmare A, McKevitt M, Jordan R, Guo Y, German P, Porter DP, Gossage DL, Watkins TR, Marty FM, Chien JW, Boeckh M. A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients. Clin Infect Dis. 2020 Dec 31;71(11):2777-2786. doi: 10.1093/cid/ciz1166.

  PMID: 31793991 DERIVED

MeSH Terms

Conditions

Respiratory Tract Infections

Interventions

presatovir

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  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: September 29, 2014
• First Posted: October 1, 2014
• Study Start: January 23, 2015
• Primary Completion: July 14, 2017
• Study Completion: July 14, 2017
• Last Updated: August 6, 2018
• Results First Posted: August 6, 2018

Record last verified: 2018-07

Locations

BR (7); TW (4); SG (2); NL (2); CH (1); IL (6); DE (1); FR (4); US (27); CA (2); GB (2); SE (1); ES (1); AU (3); KR (5)