Presatovir in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract

NCT02254421 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-218-15022014-002475-29
• Study Type: interventional
• Target: 60
• Locations: 5 countries
• Sites: 17

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 lower respiratory tract infection (LRTI).

Conditions

Respiratory Syncytial Virus Infection

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Time-weighted Average Change in Nasal Respiratory Syncytial Viral (RSV) Load From Baseline 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 factors.

  Baseline to Day 9

Secondary Outcomes (3)

• Number of Supplemental O2-Free Days Through Day 28

  Up to Day 28

• Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28

  Up to Day 28

• Percentage of All-Cause Mortality Among Participants Through Day 28

  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 to match 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: 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

Placebo to match presatovir 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
• Evidence of new abnormalities on chest X-ray obtained \< 48 hours prior to screening, determined to be consistent with LRTI by the local radiologist, relative to the most recent previous chest X-ray. If chest X-ray is not available, a chest X-ray must be obtained for screening.
• Documented RSV in both the upper (eg, nasal swab, nasopharyngeal swab, nasal wash) and lower (eg, induced sputum, bronchoalveolar lavage, lung biopsy, but not spontaneous sputum) respiratory tract as determined by local testing (eg, polymerase chain reaction, direct fluorescence antibody, respiratory viral panel assay, or culture). All samples must have been collected ≤ 6 days prior to Day 1, or as determined at screening as per protocol.
• An informed consent document signed and dated by the participant or a legal guardian of the participant and 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
• Use of a moderate or strong cytochrome P450 enzyme inducer including but not limited to rifampin, St. John's Wort, carbamazepine, phenytoin, efavirenz, bosentan, etravirine, modafinil, and nafcillin, within 2 weeks prior to the first dose of study drug
• 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 conditions:
• Requiring invasive mechanical ventilation at the time of randomization
• Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus, or coronavirus), from the lower respiratory tract sample as determined by local testing
• 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 individuals without an NG 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (17)

City of Hope

Duarte, California, United States

Location

University of Chicago

Chicago, Illinois, United States

Location

John Hopkins

Baltimore, Maryland, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Location

University of Michigan

Ann Arbor, Michigan, United States

Location

University of Minnesota

Minneapolis, Minnesota, United States

Location

New York Weill Cornell Medical Center

New York, New York, United States

Location

Duke University

Durham, North Carolina, United States

Location

MD Anderson Cancer Center

Houston, Texas, United States

Location

Fred Hutchison Cancer Research Center

Seattle, Washington, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Location

Hopital Saint-Louis, APHP

Paris, France

Location

Hopital Foch

Suresnes, France

Location

CHU de Bordeaux

Talence, 33404, France

Location

Seoul Saint Mary's Hospital

Seoul, South Korea

Location

Karolinska Institutet

Stockholm, Sweden

Location

University Clinical Basel

Basel, Switzerland

Location

Related Publications (1)

• Marty FM, Chemaly RF, Mullane KM, Lee DG, Hirsch HH, Small CB, Bergeron A, Shoham S, Ljungman P, Waghmare A, Blanchard E, Kim YJ, McKevitt M, Porter DP, Jordan R, Guo Y, German P, Boeckh M, Watkins TR, Chien JW, Dadwal SS. A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Lower Respiratory Tract. Clin Infect Dis. 2020 Dec 31;71(11):2787-2795. doi: 10.1093/cid/ciz1167.

  PMID: 31915807 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections

Interventions

presatovir

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

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 31, 2015
• Primary Completion: April 17, 2017
• Study Completion: April 17, 2017
• Last Updated: September 24, 2018
• Results First Posted: May 11, 2018

Record last verified: 2018-05

Locations

US (11); SE (1); KR (1); CH (1); FR (3)