A randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and efficacy of oral RSV604 in healthy adults experimentally infected with respiratory syncytial virus

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000790-38-GB
• Date of registration: 22/07/2008
• Prospective Registration: No
• Primary sponsor: Novartis Pharma Services AG
• Public title: A randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and efficacy of oral RSV604 in healthy adults experimentally infected with respiratory syncytial virus
• Scientific title: A randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and efficacy of oral RSV604 in healthy adults experimentally infected with respiratory syncytial virus
• Date of first enrolment: 01/07/2008
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000790-38
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
- Healthy male and female subjects age 18 to 45 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. Good general health status will also be determined by a screening evaluation no greater than 45 days prior to the quarantine and challenge phase.
- At Screening, and Baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three (3) minutes, and again after three (3) minutes in the standing position. Vital signs should be within the following ranges:
• oral body temperature between 35.0-37.5 °C
• systolic blood pressure, 90-145 mm Hg
• diastolic blood pressure, 50-95 mm Hg
• pulse rate, 40 - 95 bpm
Vital signs will be taken with the subject resting quietly in a seated position for the remaining asessments.
When blood pressure and pulse will be taken again after 3 minutes standing, there shall be no more than a 20 mm Hg drop in systolic or 10 mm Hg drop in diastolic blood pressure and increase in heart rate (>20 bpm).
All blood pressure measurements at other time-points should be assessed with the subject seated, unless stated otherwise in the protocol design, and utilizing the same arm for each determination.
- Female subjects must be of non-childbearing potential as defined below:
Female subjects must have been surgically sterilized at least 6 months prior to screening. Surgical sterilization procedures must be supported with clinical documentation made available to sponsor and noted in the Relevant Medical History/Current Medical Conditions section of the CRF.
OR
Postmenopausal women must have no regular menstrual bleeding for at least 1 year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40 IU/L at screening.
- Male subjects must be using methods of contraception, (e.g. spermicidal gel plus condom) for the entire duration of the study, up to the Study Completion visit, and refrain from fathering a child in the three months following the last study drug administration.
- Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 to 32 kg/m2. See Appendix 6 of this protocol for BMI ranges.
- Able to communicate well with the investigator, to understand and comply with the requirements of the study. Understand and sign the written informed consent and availability for the required study period, ability to attend scheduled study visits, and willingness to participate in the inpatient challenge.
- Able to tolerate nasal wash procedure.
- A serum neutralizing titer in the lower 50% of the reference laboratory range. This range will be determined using the titers of all samples measured within 160 days of entry. Thus, subjects with titers in the lower half of all screened subjects are preferentially enrolled.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Presence of significant acute or chronic, uncontrolled medical or psychiatric illness.
- Any viral illness of the upper respiratory tract occurring within 60 days of Day 0.
- Significant illness or respiratory infection within two (2) weeks prior to initial dosing.
- Heavy smokers defined as a 10 pack year history.
- Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing.
- Participation in any clinical investigation within four (4) weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations.
- Receipt of any investigational drug within three (3) months.
- A past medical history of clinically significant ECG abnormalities.
- Recent (within the last three [3] years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc).
- Recent (within the last three [3] years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated).
- History of multiple and recurring allergies, or allergy to the investigational compound being used in this study.
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
- Evidence of urinary obstruction or difficulty in voiding at screening.
- Total WBC count which falls outside the range of 4500–11,000/µl, or platelets <100,000/µl at screening.
- Any laboratory test which is abnormal and which is deemed by the investigator(s) to be clinically significant.
- History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result.
- A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.
- History of drug or alcohol abuse within the 12 months prior to study start.
- Concern by the clinician of ability to follow the study protocol procedures.
- Subject is type I or type II diabetic.
- Known IgA deficiency, immotile cilia syndrome, or Kartagener’s syndrome.
- Health care workers (including doctors, nurses, medical students and allied healthcare professionals) anticipated to have patient contact within two weeks of viral challenge.
- Presence of household member or close contact (for an additional two weeks after discharge from the isolation facility) who is: (a) less than 3 years of age; (b) any person with any known immunodeficiency; (c) any person receiving immunosuppressant medications; (d) any person undergoing or soon to undergo cancer chemotherapy within 28 days of challenge; (e) any person who has diagnosed emphysema or COPD, is elderly residing in a nursing home, or with severe lung disease; or (f) any person who has received a transplant (bone marrow or solid organ).


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

Health Condition(s) or Problem(s) studied

infection with respiratory syncytial virus

Intervention(s)

Product Name: RSV 604
Product Code: RSV 604
Pharmaceutical Form: Oral solution
INN or Proposed INN: not yet established
CAS Number: 676128-63-5
Current Sponsor code: RSV604
Other descriptive name: RSV604 benzensulfonate monohydrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Product Name: RSV 604
Product Code: RSV 604
Pharmaceutical Form: Oral solution
INN or Proposed INN: not yet established
CAS Number: 676128-63-5
Current Sponsor code: RSV604
Other descriptive name: RSV604 benzensulfonate monohydrate
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 450-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: - To evaluate the antiviral activity of RSV604, given orally, on nasal RSV load, as measured by RT-PCR, in healthy adults experimentally inoculated with a challenge virus of RSV.
- To evaluate the safety of RSV604 when given on a 5-day regimen to infected healthy adults

Primary end point(s): Viral load, scores to be defined by nasal RSV load, as measured by RT-PCR

Secondary Objective: - To determine the effect of RSV604 on symptom score as well as time to resolution of viral shedding after experimental RSV challenge.
- To explore the relationship of the timing of the administration of RSV604 to potential effects on RSV when given at different intervals after challenge.
- To determine the pharmacokinetics of RSV604 in the setting of experimental infection.
- To explore the exposure-response relationships between RSV604 plasma levels and antiviral activity and symptom score.

Secondary ID(s)

CRSV 604A 2203