E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Respiratory Syncytial Virus (RSV) infection |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10061603 |
E.1.2 | Term | Respiratory syncytial virus infection |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the ability of RSV604 to significantly reduce nasopharyngeal viral load during 5 days of intravenous therapy compared with placebo in immunocompromised adult patients with evidence of RSV infection. To determine the safety and tolerability of RSV604 when administered intravenously in immunocompromised adult patients with RSV infection. |
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E.2.2 | Secondary objectives of the trial |
• To explore for exposure-response relationships between RSV604 plasma levels and viral load reduction. • To assess the duration of RSV shedding in response to RSV604 versus placebo when combined with standard of care supportive therapy. • To evaluate clinical outcome in response to RSV604 therapy.
Exploratory objectives • To perform exploratory pharmacogenetic assessments to examine whether individual genetic variation in genes relates to the response to RSV604 versus placebo. • To asses if inflammatory cytokines and chemokines in serum can be used as biomarkers predictive of severity and progression of RSV infection and response to RSV604. • To assess change in FEV1 from Day 1 to Day 5 in response to RSV604 therapy.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evidence of RSV infection in patients who are immunocompromised based on underlying disease, disease treatment or immunosuppressive therapy, excluding HIV patients. This includes patients with evidence of RSV infection who meet any one of the following conditions: • Allogeneic stem cell transplant recipients • Autologous stem cell transplant recipients within one year of transplant • Lung, heart, kidney or heart-lung transplant recipients • Patients receiving chemotherapy or immunocompromised from a hematological malignancy (leukemia and lymphoma) • Solid tumor patients with advanced immunosuppressive regimens, as determined by the investigator (e.g. renal cell carcinoma, metastatic malignant melanoma) 2. Age 18 years or greater with no evidence of moderate to severe CNS depressed function. 3. Weight must be between 40 – 140 kg, inclusive. 4. Female subjects of child bearing potential must be using a double-barrier local contraception, i.e. intra-uterine device plus condom, or spermicidal gel plus condom until end of study. OR: Postmenopausal women must have no regular menstrual bleeding for at least 1 years prior to inclusion. OR: 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. 5. Male subjects must be using a double-barrier local contraception, i.e., spermicidal gel plus condom, for the entire duration of the study, up to Study Completion visit,. 6. Able to communicate well with the investigator, to understand and comply with the requirements of the study. Able to understand and sign the written informed consent.
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E.4 | Principal exclusion criteria |
1. Participation in experimentally unlicensed therapeutic antiviral investigation within one week prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 2. Prior use of ribavirin within 2 weeks. 3. History of active or recent significant hemolysis. 4. Documented history of allergy to benzodiazepines. 5. History of a positive HIV (ELISA and Western blot) test results. If results are older than 6 months, another HIV test must be performed. 6. Significant hepatic impairment (alanine transaminase (ALT) >3x upper level of normal (ULN), total bilirubin >3x ULN). 7. Significant renal impairment (Creatinine clearance less than 65% of normal as calculated by the Cockcroft-Gault method). (Cockcroft and Gault, 1976) 8. Past medical history of clinically significant ECG abnormalities or a family history (grandparents, parents and siblings) of a prolonged QT-interval syndrome. 9. Patients, who in the opinion of the investigator, should not participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Decrease in nasopharyngeal RSV viral load |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 16 |