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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02949011




Registration number
NCT02949011
Ethics application status
Date submitted
27/10/2016
Date registered
31/10/2016
Date last updated
19/11/2019

Titles & IDs
Public title
Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Patients With Influenza at High Risk of Influenza Complications
Scientific title
A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188 Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Patients With Influenza at High Risk of Influenza Complications
Secondary ID [1] 0 0
2016-002688-32
Secondary ID [2] 0 0
1602T0832
Universal Trial Number (UTN)
Trial acronym
CAPSTONE 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Baloxavir Marboxil
Treatment: Drugs - Placebo to Baloxavir Marboxil
Treatment: Drugs - Oseltamivir
Treatment: Drugs - Placebo to Oseltamivir

Experimental: Baloxavir Marboxil - Participants received either 40 mg or 80 mg of baloxavir marboxil orally on Day 1 based on body weight of < 80 kg or = 80 kg at Screening, respectively. Participants also received placebo to oseltamivir orally twice a day (BID) on Days 1 to 5.

Active Comparator: Oseltamivir - Participants received 75 mg oseltamivir twice a day on Days 1 to 5 and placebo to baloxavir marboxil on Day 1.

Placebo Comparator: Placebo - Participants received placebo to baloxavir marboxil on Day 1 and placebo to oseltamivir orally twice a day on Days 1 to 5.


Treatment: Drugs: Baloxavir Marboxil
Tablets taken orally

Treatment: Drugs: Placebo to Baloxavir Marboxil
Matching tablets taken orally

Treatment: Drugs: Oseltamivir
Capsules taken orally

Treatment: Drugs: Placebo to Oseltamivir
Matching placebo capsules taken orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Improvement of Influenza Symptoms
Timepoint [1] 0 0
From Day 1 pretreatment up to Day 14
Secondary outcome [1] 0 0
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point
Timepoint [1] 0 0
Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Secondary outcome [2] 0 0
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point
Timepoint [2] 0 0
Days 2, 3, 4 (optional), 5, 6 (optional), and 9.
Secondary outcome [3] 0 0
Change From Baseline in Virus Titer at Each Time Point
Timepoint [3] 0 0
Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Secondary outcome [4] 0 0
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point
Timepoint [4] 0 0
Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Secondary outcome [5] 0 0
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer
Timepoint [5] 0 0
Day 1 to Day 9
Secondary outcome [6] 0 0
Area Under the Curve (AUC) Adjusted by Baseline in Viral RNA
Timepoint [6] 0 0
Day 1 to Day 9
Secondary outcome [7] 0 0
Time to Cessation of Viral Shedding Determined by Virus Titer
Timepoint [7] 0 0
Day 1 to Day 9
Secondary outcome [8] 0 0
Time to Cessation of Viral Shedding Determined by Virus RNA
Timepoint [8] 0 0
Day 1 to Day 9
Secondary outcome [9] 0 0
Percentage of Participants Whose Symptoms Were Improved at Each Time Point
Timepoint [9] 0 0
12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment
Secondary outcome [10] 0 0
Time to Alleviation of Symptoms
Timepoint [10] 0 0
Initiation of study treatment up to Day 14
Secondary outcome [11] 0 0
Time to Improvement of the Four Systemic Symptoms
Timepoint [11] 0 0
Initiation of study treatment up to Day 14
Secondary outcome [12] 0 0
Time to Improvement of the Three Respiratory Symptoms
Timepoint [12] 0 0
Initiation of study treatment up to Day 14
Secondary outcome [13] 0 0
Time to Resolution of Fever
Timepoint [13] 0 0
Initiation of study treatment up to Day 14
Secondary outcome [14] 0 0
Percentage of Participants Reporting Normal Temperature at Each Time Point
Timepoint [14] 0 0
12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment
Secondary outcome [15] 0 0
Body Temperature at Each Time Point
Timepoint [15] 0 0
12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment
Secondary outcome [16] 0 0
Time to Improvement of Individual Symptoms
Timepoint [16] 0 0
Initiation of study treatment up to Day 14
Secondary outcome [17] 0 0
Time to Return to Preinfluenza Health Status
Timepoint [17] 0 0
Baseline to Day 14
Secondary outcome [18] 0 0
Percentage of Participants Requiring Systemic Antibiotics for Infections Secondary to Influenza Infection
Timepoint [18] 0 0
Day 2 to Day 22
Secondary outcome [19] 0 0
Percentage of Participants With Influenza-related Complications
Timepoint [19] 0 0
Day 1 to Day 22
Secondary outcome [20] 0 0
Percentage of Participants With Adverse Events (AEs)
Timepoint [20] 0 0
From first dose of study drug to Day 22

Eligibility
Key inclusion criteria
1. Patients or their legal guardians who provide written informed consent to participate
in the study on a voluntary basis. For adolescent patients, informed consent/assent of
voluntary participation should be obtained in accordance with local requirements.

2. Male or female patients = 12 years at the time of signing the informed consent/assent
form.

3. Patients with a diagnosis of influenza confirmed by all of the following:

1. Fever = 38ºC (axillary) during the predose examinations or within the 4 hours
prior if antipyretics were taken

2. A positive rapid influenza diagnostic test (RIDT) result OR A patient with a
negative RIDT may be enrolled if the patient reports contact with a known case of
influenza within the prior 7 days and all other inclusion criteria are met.

3. At least 1 each of the following general and respiratory symptoms associated with
influenza is present with a severity of moderate or greater:

i. General symptoms (headache, feverishness or chills, muscle or joint pain, or
fatigue) ii. Respiratory symptoms (cough, sore throat, or nasal congestion)

4. The time interval between the onset of symptoms and the predose examinations is 48
hours or less. The onset of symptoms is defined as either:

1. Time of the first increase in body temperature (an increase of at least 1ºC from
normal body temperature)

2. Time when the patient experiences at least 1 new general or respiratory symptom

5. If a women of childbearing potential, agrees to use a highly effective method of
contraception for 3 months after the first dose of study drug

6. Patients will be considered at high risk* of influenza complications due to the
presence of at least 1 of the following inclusion criteria:

1. Asthma or chronic lung disease (such as chronic obstructive pulmonary disease or
cystic fibrosis)

2. Endocrine disorders (including diabetes mellitus)

3. Residents of long-term care facilities (eg, nursing homes)

4. Compromised immune system (including patients receiving corticosteroids not
exceeding 20 mg of prednisolone or equivalent, and patients being treated for
human immunodeficiency virus [HIV] infection with a CD4 count > 350 cells/mm³
within the last 6 months)

5. Neurological and neurodevelopmental disorders (including disorders of the brain,
spinal cord, peripheral nerve, and muscle, eg, cerebral palsy, epilepsy [seizure
disorders], stroke, muscular dystrophy, or spinal cord injury)

6. Heart disease (such as congenital heart disease, congestive heart failure, or
coronary artery disease), excluding hypertension without any other heart-related
symptoms

7. Adults aged = 65 years

8. American Indians and Alaskan Natives

9. Blood disorders (such as sickle cell disease)

10. Metabolic disorders (such as inherited metabolic disorders and mitochondrial
disorders)

11. Morbid obesity (body mass index = 40 kg/m²)

12. Women who are within 2 weeks postpartum and are not breastfeeding
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with severe influenza virus infection requiring inpatient treatment.

2. Patients with known allergy to oseltamivir (Tamiflu®).

3. Patients unable to swallow tablets or capsules.

4. Patients who have previously received baloxavir marboxil.

5. Patients weighing = 40 kg.

6. Patients who have been exposed to an investigational drug within 30 days prior to the
predose examinations.

7. Women who are pregnant, breastfeeding, or have a positive pregnancy test at the
predose examinations. The following female patients who have documentation of either a
or b below do not need to undergo a pregnancy test at the predose examinations:

1. Postmenopausal women (defined as cessation of regular menstrual periods for 2
years or more and confirmed by a follicle-stimulating hormone test)

2. Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or
tubal ligation

8. Patients with concurrent infections at the predose examinations requiring systemic
antimicrobial therapy.

9. Patients with liver disease associated with hepatic impairment.

10. Patients with cancer within the last 5 years (unless nonmelanoma skin cancer).

11. Patients with untreated HIV infection or treated HIV infection with a CD4 count below
350 cells/mm3 in the last 6 months.

12. Patients with immunosuppression following organ or bone marrow transplants.

13. Patients exceeding 20 mg of prednisolone or equivalent dose of chronic systemic
corticosteroids.

14. Patients who have received peramivir, laninamivir, oseltamivir, zanamivir,
rimantadine, umifenovir or amantadine within 30 days prior to the predose
examinations.

15. Patients who have received an investigational monoclonal antibody for a viral disease
in the last year.

16. Patients with known creatinine clearance = 60 mL/min.

17. Patients who, in the opinion of the investigator, would be unlikely to comply with
required study visits, self-assessments, and interventions

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/04/2018
Sample size
Target
Accrual to date
Final
2184
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Shionogi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the efficacy of a single, oral dose of
baloxavir marboxil compared with placebo by measuring the time to improvement of influenza
symptoms in patients with influenza presenting within 48 hours of symptom onset.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02949011
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Shionogi Clinical Trials Administrator Clinical Support Help Line
Address 0 0
Shionogi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries