FREESIA: Effects of JNJ-53718678 in Adult and Adolescent Participants Who Had a Hematopoietic Stem Cell Transplantation and Who Are Infected With Respiratory Syncytial Virus (RSV)

Sponsor

Janssen Sciences Ireland UC (Industry)

Overall Status

Terminated

CT.gov ID

NCT04056611

Collaborator

(none)

Enrollment

Locations

Arms

25.3

Actual Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of JNJ-53718678 on the development of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTIs) in adult hematopoietic stem cell transplant (HSCT) recipients with RSV upper RTI.

Condition or Disease	Intervention/Treatment	Phase
Respiratory Syncytial Virus Infections	Drug: JNJ-53718678 250 mg Drug: Placebo Drug: JNJ-53718678 125 mg	Phase 2

Detailed Description

RSV is recognized as major respiratory pathogen in infants and young children and causes upper and lower respiratory illness among all age groups, often going undiagnosed. Immunocompromised (IC) participants have a reduced ability to combat infection due to an impaired or weakened immune system. Within the IC population, HSCT recipients are generally regarded as having a particularly high risk for more severe disease caused by RSV, representing a substantial unmet need for antiviral treatment of RSV infections in this participant population. JNJ-53718678 is an investigational, potent, small molecule, respiratory syncytial virus (RSV)-specific fusion inhibitor. The study will include a Screening Period (Day -2 to Day 1), a Treatment Period (Day 1 to Day 21), and a Follow-up Period (1 year). Assessments like chest X-ray, pulse/heart rate, respiratory rate, electrocardiogram (ECG), etc will be performed. Safety and efficacy will be assessed through the study. The total study duration for each participant will be approximately 49 days.

Study Design

Study Type:

Interventional

Actual Enrollment :

3 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Clinical Outcomes, Antiviral Activity, Safety, Tolerability, Pharmacokinetics, and Pharmacokinetics/Pharmacodynamics of JNJ-53718678 in Adult and Adolescent Hematopoietic Stem Cell Transplant Recipients With Respiratory Syncytial Virus Infection of the Upper Respiratory Tract

Actual Study Start Date :

Dec 26, 2019

Actual Primary Completion Date :

Dec 22, 2021

Actual Study Completion Date :

Feb 4, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adult cohort: JNJ-53718678 or Placebo Participants greater than or equal to (>=) 18 to less than or equal to (<=) 75 years of age will receive 250 milligram (mg) JNJ-53718678 twice daily (bid) for 21 days (without coadministration with moderate or strong CYP3A4 inhibitors), or 125 mg JNJ-53718678 bid for 21 days (coadministered with moderate or strong CYP3A4 inhibitors with the exception of posaconazole), or 125 mg once daily (qd) for 21 days (when coadministered with posaconazole), or matching placebo for 21 days.	Drug: JNJ-53718678 250 mg JNJ-53718678 250 mg will be administered orally. Drug: Placebo Matching placebo will be administered orally. Drug: JNJ-53718678 125 mg JNJ-53718678 125 mg will be administered orally.
Experimental: Adolescent cohort: JNJ-53718678 or Placebo Participants >=13 to <18 years of age will receive 250 mg JNJ-53718678 bid for 21 days (without coadministration with moderate or strong CYP3A4 inhibitors), or 125 mg JNJ-53718678 bid for 21 days (coadministered with moderate or strong CYP3A4 inhibitors with the exception of posaconazole), or 125 mg qd for 21 days (when coadministered with posaconazole), or matching placebo for 21 days.	Drug: JNJ-53718678 250 mg JNJ-53718678 250 mg will be administered orally. Drug: Placebo Matching placebo will be administered orally. Drug: JNJ-53718678 125 mg JNJ-53718678 125 mg will be administered orally.

Arm

Intervention/Treatment

Experimental: Adult cohort: JNJ-53718678 or Placebo

Participants greater than or equal to (>=) 18 to less than or equal to (<=) 75 years of age will receive 250 milligram (mg) JNJ-53718678 twice daily (bid) for 21 days (without coadministration with moderate or strong CYP3A4 inhibitors), or 125 mg JNJ-53718678 bid for 21 days (coadministered with moderate or strong CYP3A4 inhibitors with the exception of posaconazole), or 125 mg once daily (qd) for 21 days (when coadministered with posaconazole), or matching placebo for 21 days.

Drug: JNJ-53718678 250 mg

JNJ-53718678 250 mg will be administered orally.

Drug: Placebo

Matching placebo will be administered orally.

Drug: JNJ-53718678 125 mg

JNJ-53718678 125 mg will be administered orally.

Experimental: Adolescent cohort: JNJ-53718678 or Placebo

Participants >=13 to <18 years of age will receive 250 mg JNJ-53718678 bid for 21 days (without coadministration with moderate or strong CYP3A4 inhibitors), or 125 mg JNJ-53718678 bid for 21 days (coadministered with moderate or strong CYP3A4 inhibitors with the exception of posaconazole), or 125 mg qd for 21 days (when coadministered with posaconazole), or matching placebo for 21 days.

Drug: JNJ-53718678 250 mg

JNJ-53718678 250 mg will be administered orally.

Drug: Placebo

Matching placebo will be administered orally.

Drug: JNJ-53718678 125 mg

JNJ-53718678 125 mg will be administered orally.

Outcome Measures

Primary Outcome Measures

Proportion of Participants who Develop Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI) [Up to Day 28]
The proportion of participants who develop RSV LRTI through Visit Day 28 per the Endpoint Adjudication Committee (EAC) assessment will be reported.

Secondary Outcome Measures

Proportion of Participants who Develop RSV-associated Lower Respiratory Tract Complication (LRTC) [Up to Day 28]
The proportion of participants who develop RSV-associated LRTC through Visit Day 28 per the EAC's assessment will be reported.
Number of Participants with Adverse Events (AEs) [Up to 49 days]
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
Percentage of Participants with Abnormal Clinical Laboratory Findings [Up to 49 days]
Percentage of participants with abnormal clinical laboratory findings will be reported.
Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings [Up to 49 days]
Percentage of participants with abnormal ECGs findings will be reported.
Percentage of Participants with Abnormal Vital Signs Findings [Up to 49 days]
Percentage of participants with abnormal vital signs findings will be reported.
Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment [Up to 49 days]
The proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, (all-cause Mortality) [Up to 49 days]
Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, (all-cause mortality) will be reported.
Proportion of Participants Progressing to Death (All-cause Mortality), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment [Up to 49 days]
Proportion of participants progressing to death (all-cause mortality), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Proportion of Participants Progressing to Death (All-cause Mortality) [Up to 1 year]
Proportion of participants progressing to death (all-cause mortality) will be reported.
Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment [Up to 49 days]
Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) [Up to 49 days]
Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) will be reported.
Number of Supplemental Oxygen (O2) Free Days Through Day 28 [Through Day 28]
Number of supplemental O2 free days will be reported.
Incidence of Supplemental Oxygen Requirement [Up to 28 days]
Incidence of supplemental oxygen requirement in participants will be reported.
Duration of Supplemental Oxygen [Up to 28 days]
Duration of supplemental oxygen requirement in participants will be reported.
Change from Baseline in Respiratory Rate [Baseline up to 49 days]
Change from baseline in respiratory rate as measured by the investigator during scheduled visits will be reported.
Change from Baseline in Heart Rate [Baseline up to 49 days]
Change from baseline in heart rate as measured by the investigator during scheduled visits will be reported.
Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2) [Baseline up to 49 days]
Change from baseline in SpO2 as measured by the investigator during scheduled visits will be reported.
Change from Baseline in Body Temperature [Baseline up to 49 days]
Change from baseline in body temperature as measured by the investigator during scheduled visits will be reported.
Proportion of Participants Hospitalized (of Participants who Were not Hospitalized at Baseline) [Up to 1 year]
Proportion of participants hospitalized (of participants who were not hospitalized at baseline) will be reported.
Proportion of Participants Re-hospitalized [Up to 1 year]
Proportion of participants re-hospitalized (of participants who were hospitalized at baseline and discharged during the study and of participants who were not hospitalized at baseline, required hospitalization, and were discharged during the study) will be reported.
Total Length of Hospital Stay [Up to 49 days]
Total length of hospital stay (time in hospital from first dosing) will be reported.
Total Time in the Intensive Care Unit (ICU) [Up to 49 days]
Total time in the ICU (time in ICU from first dosing) will be reported.
Incidence of Grade 3 and Grade 4 Adverse Events (AEs) [Up to 49 days]
Incidence of Grade 3 and Grade 4 AEs will be assessed by system organ class where Grade 3: Severe and Grade 4: Life-threatening.
Incidence of Respiratory AEs [Up to 49 days]
Incidence of respiratory AEs will be reported.
Incidence of Thoracic-related AEs [Up to 49 days]
Incidence of thoracic-related AEs will be reported.
Incidence of Antibiotic use in Participants who Develop and in Those who do not Develop RSV LRTI or RSV-Associated LRTC per the EAC's Assessment [Up to 49 days]
Incidence of antibiotic use in participants who develop and in those who do not develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.
Time to Resolution of Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale [Up to 49 days]
Time to resolution of symptoms, assessed through an instrument for participant-reported symptoms (RiiQ Symptom Scale) will be reported.
Change from Baseline in Severity of Symptoms Reported by Participants in the RiiQ Symptom Scale Through Day 28 [Baseline up to Day 28]
Change from baseline in severity of symptoms reported by participants in the RiiQ symptom scale through Day 28 will be reported.
Time to Resolution of Respiratory Illness as Assessed by Patient Global Impression of Severity (PGI-S) Scale [Up to 49 days]
Time to resolution of respiratory illness, through the PGI-S Scale, will be reported.
Change from Baseline in Patient Global Impression of Health (PGI-H) Scale Through Day 28 [Baseline up to Day 28]
Change from baseline in PGI-H scale through Day 28 will be reported.
Change from Baseline in Patient Global Impression of Change (PGI-C) Scale Through Day 28 [Baseline up to Day 28]
Change from baseline in PGI-C scale through Day 28 will be reported.
Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours Postdose (AUC [0-24]) of JNJ-53718678 [Up to 24 hours postdose (on Days 1 and 8)]
AUC (0-24h) is defined as area under the plasma concentration-time curve from time 0 to 24 hours postdose.
Trough Plasma Concentration (Ctrough) of JNJ-53718678 [Predose on Days 1 and 8]
Ctrough is defined as the observed plasma concentration before dosing or at the end of the dosing interval.
Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678 [Day 1]
Cmax is defined as the maximum observed plasma concentration of JNJ-53718678 in the dosing interval.
Association of Plasma Concentration-time Data of JNJ-53718678 and Antiviral Activity [Up to 49 days]
The potential association of plasma concentration-time data of JNJ-53718678 with antiviral activity (RSV viral kinetics) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
Association of Plasma Concentration-time Data of JNJ-53718678 and Safety Parameters [Up to 49 days]
The potential association of plasma concentration-time data of JNJ-53718678 with selected safety (including AEs and laboratory abnormalities) parameters will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
Association of Plasma Concentration-time Data of JNJ-53718678 and Clinical Outcomes [Up to 49 days]
The potential association of plasma concentration-time data of JNJ-53718678 with clinical outcomes (proportion of participants developing LRTI) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.
RSV Viral Load and Change from Baseline Over Time [Baseline up to Day 28]
RSV viral load and change from baseline over time will be measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in the mid-turbinate nasal swab specimens.
RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 8, 11, 15, 22 and 28 [Baseline up to Days 8, 11, 15, 22 and 28]
RSV viral load AUC will be determined by quantitative qRT-PCR assay of nasal swabs.
Time to Undetectable RSV Viral Load [Up to 49 days]
Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.
Proportion of Participants with Undetectable RSV Viral Load at Each Timepoint [Up to 49 days]
Proportion of participants with undetectable RSV viral load at each time point throughout the study will be reported.
Change from Baseline for the Health-related Quality of Life (HRQOL) as Assessed by 5-level EuroQol 5-Dimension (EQ-5D-5L) Through Day 28 [Baseline up to Day 28]
Change from baseline for the HRQOL assessment as assessed through the EQ-5D-5L through Day 28 will be reported.
Change from Baseline for the HRQOL as Assessed by RiiQ Impact Scales Through Day 28 [Baseline up to Day 28]
Change from baseline for the HRQOL assessment as assessed through RiiQ impact scales through Day 28 will be reported.
Change from Baseline in the RSV F Gene Sequence [Baseline up to 49 days]
Change from baseline in the RSV F gene sequence will be reported.

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Received an autologous or allogeneic hematopoietic stem cell transplant (HSCT) using any conditioning regimen
Absolute lymphocyte count (ALC) less than (<) 1,000 cells/microliter (mL)
Participant has laboratory confirmed RSV diagnosis within 48 hours of randomization
New onset of at least 1 of the following respiratory symptoms within 4 days prior to the anticipated start of dosing nasal congestion, rhinorrhea, cough or pharyngitis (sore throat), and/or worsening of one of these chronic (associated with previously existing diagnosis, example, chronic rhinorrhea, seasonal allergies, chronic lung disease) respiratory symptoms within 4 days prior to the anticipated start of dosing
Peripheral capillary oxygen saturation (SpO2) greater than or equal to (>=) 92 percent (%) on room air

Exclusion Criteria:

Admitted to the hospital primarily for a lower respiratory tract disease of any cause as determined by the investigator
Requires supplemental oxygen at Screening or any time between Screening and randomization
Documented to be positive for other respiratory viruses (limited to influenza, parainfluenza, human rhinovirus, adenovirus, human metapneumovirus, or coronavirus) within 7 days prior to or at the Screening visit, if determined by local SOC testing (additional testing is not required)
Clinically significant bacteremia or fungemia within 7 days prior to or at Screening that has not been adequately treated, as determined by the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
2	Henry Ford Hospital - Hematology/oncology	Detroit	Michigan	United States	48202
3	University Of Minnesota	Minneapolis	Minnesota	United States	55455
4	Northwell Health Cancer Institute	Lake Success	New York	United States	11042
5	Weill Cornell Medical College	New York	New York	United States	10065
6	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
7	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
8	Baylor Scott & White Research Institute	Dallas	Texas	United States	75246
9	MD Anderson Cancer Center - University of Texas	Houston	Texas	United States	77030
10	Hospital Español De Bahia Blanca	Bahia Blanca		Argentina	8000
11	Hospital Italiano de La Plata	Ciudad De La Plata		Argentina	B1900AX
12	Sanatorio Allende	Cordoba		Argentina	X5000JHQ
13	Hospital Privado-Universitario de Cordoba	Cordoba		Argentina	X5016KEH
14	Clinica Mayo de UMCB	San Miguel de Tucuman		Argentina	T4000IHE
15	Peter MacCallum Cancer Centre	Melbourne		Australia	3000
16	Royal Melbourne Hospital	Melbourne		Australia	3050
17	Westmead Hospital	Westmead		Australia	2145
18	AZ Sint-Jan	Brugge		Belgium	8000
19	Jules Bordet Institute	Brussels		Belgium	1000
20	UZ Brussel	Brussels		Belgium	1090
21	UZ Gent	Gent		Belgium	9000
22	UZ Leuven	Leuven		Belgium	3000
23	CHU de Liège	Liege		Belgium	4000
24	Jessa Ziekenhuis	Limburg		Belgium	3500
25	Hospital de Amor - Barretos	Barretos		Brazil	14784-400
26	Hospital de Clinicas da Universidade Federal De Minas Geraisnas Gerais	Belo Horizonte		Brazil	30130-100
27	Cepon - Centro De Pesquisas Oncologicas	Florianópolis		Brazil	88034-000
28	Hospital Universitario Walter Cantidio	Fortaleza		Brazil	60430-372
29	Fundacao Amaral Carvalho	Jau		Brazil	17210-080
30	Hospital de Clínicas de Porto Alegre	Porto Alegre		Brazil	90035-007
31	Sociedade Beneficiante de Senhoras - Hospital Sirio Libanes	Sao Paulo		Brazil	01308-060
32	Hospital de Base de São José do Rio Preto	São José do Rio Preto		Brazil	15090-000
33	Hospital Beneficencia Portuguesa	São Paulo		Brazil	01321-001
34	Fundacao Antonio Prudente	São Paulo		Brazil	01508-010
35	UMHAT 'Sveti Georgi'-Plovdiv	Plovdiv		Bulgaria	4002
36	Specialized Hospital for Active Treatment of Haematologic Diseases	Sofia		Bulgaria	1756
37	Multiprofile Hospital for Active Treatment 'Sveta Marina' EAD	Varna		Bulgaria	9010
38	Hôpital d'Instruction des Armées Percy	Clamart		France	92190
39	Institut Universitaire du Cancer Toulouse - Oncopole	Toulouse		France	31059
40	Rambam Medical Center	Haifa		Israel	3525408
41	Hadassah Medical Center	Jerusalem		Israel	91120
42	Sheba Medical Center	Ramat Gan		Israel	57261
43	Sourasky (Ichilov) Medical Center	Tel Aviv		Israel	64239
44	Ospedale San Raffaele HSR Istituto Scientifico Universitario San Raffaele	Milano		Italy	20132
45	Ematologia Fondazione Univ. Policlinico Gemelli Università Cattolica del Sacro Cuore	Roma		Italy	168
46	Akita University Hospital	Akita		Japan	010-8543
47	Chiba University Hospital	Chiba		Japan	260-8677
48	Tokai University Hospital	Isehara		Japan	259-1193
49	Japanese Red Cross Society Nagano Hospital	Nagano		Japan	380-8582
50	Okayama University Hospital	Okayama		Japan	700-8558
51	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
52	Hospital Ampang	Ampang Jaya		Malaysia	68000
53	Penang General Hospital	Georgetown		Malaysia	10190
54	University Malaya Medical Centre	Kuala Lumpur		Malaysia	59100
55	Sunway Medical Centre	Petaling Jaya, Selangor		Malaysia	47500
56	Leiden University Medical Center	Leiden		Netherlands	2333 ZA
57	Hosp. Univ. Vall D Hebron	Barcelona		Spain	08035
58	Hosp. de La Santa Creu I Sant Pau	Barcelona		Spain	8041
59	Hosp. Gral. Univ. Gregorio Marañon	Madrid		Spain	28007
60	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
61	Hosp. Clinico Univ. de Salamanca	Salamanca		Spain	37007
62	Hosp. Univ. Marques de Valdecilla	Santander		Spain	39008
63	Hosp. Virgen Del Rocio	Sevilla		Spain	41013
64	Skanes universitetssjukhus	Malmö		Sweden	20502
65	Kaohsiung Medical University Hospital	Kaohsiung		Taiwan	807
66	China Medical University Hospital	Taichung		Taiwan	40447
67	National Cheng Kung University Hospital	Tainan		Taiwan	70403
68	National Taiwan University Hospital	Taipei		Taiwan	10002
69	Kings College Hospital NHS Trust	London		United Kingdom	SE5 9RS

Sponsors and Collaborators

Janssen Sciences Ireland UC

Investigators

Study Director: Janssen Sciences Ireland UC Clinical Trial, Janssen Sciences Ireland UC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Janssen Sciences Ireland UC

ClinicalTrials.gov Identifier:

NCT04056611

Other Study ID Numbers:

CR108662
53718678RSV2005
2019-001551-39

First Posted:

Aug 14, 2019

Last Update Posted:

Mar 18, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Infections

Virus Diseases

Respiratory Syncytial Virus Infections

Study Results

No Results Posted as of Mar 18, 2022