SAPPHIRE - A study to see if pimodivir in combination with standard of care treatment is useful and safe in the treatment of adolescent, adult and elderly hospitalized patients with influenza A infection.

• Register: EUCTR
• Last refreshed on: 15 September 2020
• Main ID: EUCTR2017-002156-84-LV
• Date of registration: 18/12/2017
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: SAPPHIRE - A study to see if pimodivir in combination with standard of care treatment is useful and safe in the treatment of adolescent, adult and elderly hospitalized patients with influenza A infection.
• Scientific title: A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pimodivir in Combination With the Standard-of-care Treatment in Adolescent, Adult, and Elderly Hospitalized Patients With Influenza A Infection
• Date of first enrolment: 26/02/2018
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002156-84
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Add-on design to SoC (investigator's choice: antiviral therapy and/or supportive care); If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Chile, Czech Republic, France, Germany, Hungary, India, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Peru, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female, 13 to 85 years of age, inclusive. Note: Adolescent subjects (13-17 years) will be enrolled in selected countries and study sites consistent with local regulations.
• Tested positive for influenza A infection after the onset of symptoms using a polymerase chain reaction (PCR)-based or other rapid molecular diagnostic assay.
• Requires hospitalization to treat influenza infection and/or to treat complications of influenza infection (eg, radiological signs of lower respiratory tract disease, septic shock, central nervous system [CNS] involvement, myositis, rhabdomyolysis, acute exacerbation of chronic kidney disease, severe dehydration, myocarditis, pericarditis, ischemic heart disease, exacerbation of underlying chronic pulmonary disease, including asthma, chronic obstructive pulmonary disease [COPD], decompensation of previously controlled diabetes mellitus), including subjects admitted to the intensive care unit (ICU). Note: For the purpose of the protocol, subjects admitted under “observation” status with an anticipated length of stay beyond 24 hours are eligible for enrollment.
• Enrollment and initiation of study drug treatment =96 hours after onset of influenza symptoms.
• Being on invasive mechanical ventilation or having an SpO2 <94% on room air during screening. Subjects with known pre-influenza SpO2 <94% must have an SpO2 decline =3% from pre-influenza SpO2 during screening.
• Having a screening/baseline National Early Warning Score (NEWS) of =4.

Treatment Extension Criteria - Subjects will be given the option for treatment extension in case all of the following conditions are met:
• The subject completed the 5-day treatment period.
• The subject is still hospitalized.
• The subject is on invasive mechanical ventilation or has an ongoing respiratory deficiency as evidenced by having an SpO2 <94% on room air, or in case of known pre-influenza SpO2 <94% (eg, due to COPD), the current blood oxygen saturation on room air is lower than pre-influenza infection levels by at least 3%.
• The subject is expected to derive clinical benefit from extending the treatment period, in the opinion of the investigator.
• The investigator agrees to extend treatment with the same SOC. If the SOC contained no influenza antiviral during the first treatment period, no influenza antiviral can be started in the treatment extension as part of the SOC.
Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270

Exclusion criteria:
• Received more than 3 doses of influenza antiviral medication (eg, oseltamivir [OST] or zanamivir), or any dose of ribavirin within 2 weeks, prior to first study drug intake. Received intravenous (IV) peramivir more than one day prior to screening.
• Unwilling to undergo regular nasal mid-turbinate (MT) swabs or has any physical abnormality which limits the ability to collect regular nasal MT specimens.
• Unstable angina pectoris or myocardial infarction within 30 days prior to screening (inclusive).
• Presence of clinically significant heart arrhythmias, uncontrolled, unstable atrial arrhythmia, or sustained ventricular arrhythmia, or risk factors for Torsade de Pointes syndrome.
• Known severe hepatic impairment (Child Pugh C cirrhosis) or chronic hepatitis C infection undergoing hepatitis C antiviral therapy.
• Severely immunocompromised in the opinion of the investigator (eg, known cluster of differentiation 4+ [CD4+] count <200 cells/mm3, absolute neutrophil count <750/mm3, first course of chemotherapy completed within 2 weeks prior to screening, history of stem cell transplant within 1 year prior to screening, any history of a lung transplant).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Influenza A Infection
MedDRA version: 20.1 Level: LLT Classification code 10022002 Term: Influenza A virus infection System Organ Class: 100000004862

Intervention(s)

Product Name: Pimodivir
Product Code: JNJ-63623872-ZCD
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Pimodivir
CAS Number: 1777721-70-6
Other descriptive name: JNJ-63623872-ZCD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the hospital recovery scale as assessed on Day 6.

Secondary Objective: Compare pimodivir (Pi) in combination with SOC treatment (tmt) to placebo in combination with SOC tmt (Pi + SOC tmt vs. Placebo + SOC tmt) regarding:
* Safety, tolerability
* All-cause mortality
* Incidence, duration of antibiotic tmt
* No. of subjects needing extended tmt, requiring re-hospitalization, not hospitalized at Day 6
* Time to clinical response
* Time to improvement of respiratory status
Evaluate superiority of Pi+SOC vs.Pl+SOC with respect to:
* Time in hospital, time in ICU, time on mechanical ventilation, time to return to daily activities
* Clinical outcome on hospital recovery scale
* Incidence of complications associated with influenza after start of study tmt
* Time to viral negativity a. viral load over time by qRT-PCR and viral culture
To assess PK of Pi; PK/PD relationships of Pi
Investigate:
* Acceptability (taste, swallowability) of Pi formulation in adolescents
* Emergence of viral resistance against Pi

Main Objective: The primary objective is to evaluate superiority of pimodivir in combination with standard-of-care (SOC) treatment compared to placebo in combination with SOC treatment on Day 6, with respect to the clinical outcome on the hospital recovery scale.

Timepoint(s) of evaluation of this end point: The hospital recovery scale assesses a subject’s clinical status and will be assessed as the subject’s condition on Day 6 as the primary endpoint.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-4, 6-11, 13-14: Day 33
5. Days 2-5 and 7-14
12. and 15: Day 6
16. Days 1 and 5
17 - 19: Day 19

Secondary end point(s): 1. Safety and tolerability based on assessment of adverse events (AEs), clinical laboratory assessments, 12-lead electrocardiograms (ECGs), vital signs, and peripheral capillary oxygen saturation.
2. Time from start of study drug to hospital discharge and total length of hospital stay.
3. Time from ICU admission to ICU discharge and total time in ICU.
4. Time from start to end of mechanical ventilation and total time on mechanical ventilation.
5. The hospital recovery scale as assessed each separate day from Days 2 to 14 (excluding the primary time point).
6. Time to return to daily activities.
7. Incidence of complications associated with influenza after the start of study treatment.
8. All-cause mortality.
9. Incidence and duration of antibiotic treatment.
10. The number (proportion) of subjects needing extended treatment.
11. The number (proportion) of subjects requiring re-hospitalization.
12. The number (proportion) of subjects not hospitalized at Day 6.
13. Time to clinical response.
14. Time to respiratory response.
15. PK parameters of pimodivir (ie, plasma concentration just prior to the beginning or at the end of a dosing interval [Ctrough], Cmax, tmax, and AUC12h), as determined by population PK analysis.
16. The acceptability of the pimodivir formulation in adolescents, as measured by a taste and swallowability questionnaire.
17. Time to viral negativity by qRT-PCR and viral culture.
18. Viral load over time by qRT-PCR and viral culture.
19. The emergence of viral resistance against pimodivir detected by genotyping and/or phenotyping.

Secondary ID(s)

NCT03376321

2017-002156-84-SE

63623872FLZ3001

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date: 26/01/2018
Contact: