E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Lung transplant patients with Human respiratory syncytial virus (RSV) infection |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052200 |
E.1.2 | Term | Respiratory syncytial virus infection NOS |
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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 assess the safety and tolerability of aerosolized ALN-RSV01 versus placebo administered once daily for 3 days in lung transplant patients infected with RSV |
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E.2.2 | Secondary objectives of the trial |
- Evaluate effects of ALN-RSV01 versus placebo on the clinical endpoints of RSV infection in lung transplant patients - Determine RSV infection characteristics by quantitative RT-PCR (qRT-PCR) analysis of nasal swab and sputum samples, including peak viral load, time to peak viral load, duration of viral shedding and viral AUC - Characterize plasma pharmacokinetics of aerosolized ALN-RSV01. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The study population is lung transplant patients infected with RSV. Key Inclusion Criteria include: - Adults ≥18 years old - Single or bilateral lung transplant recipients - Provide written informed consent - Greater than 90 days post current lung transplant - Rejection-free for a minimum of 1 month - Confirmed RSV infection by local laboratory’s testing methods and able to initiate study drug treatment within 3 days of positive RSV test. - If female, agrees to use appropriate double barrier contraception for a period of 30 days after the last dose of study medication. If the subject is using oral, implanted or injectable contraception, she must have been using them for at least 3 months prior to Day -3 |
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E.4 | Principal exclusion criteria |
1. Antimicrobial therapy for a known viral, bacterial, or fungal respiratory co-infection at the time of RSV diagnosis (Empiric therapy for suspected infection is permitted) 2. Bronchiolitis obliterans syndrome (BOS) Grade 3, or any stage BOS (see Appendix 4) with FEV1 that has not been stable for at least 3 months prior to onset of signs or symptoms of RSV infection. 3. Active treatment for acute graft rejection 4. Hospitalization that requires intubation or mechanical ventilation 5. Presence of tracheotomy 6. Past history of severe bronchospasm associated with aerosol drug use 7. Treatment with another investigational drug not approved in the US and/or EU, or participation in a clinical trial follow-up phase within 30 days prior to Screen (Day -3 to Day 0) 8. If female, the patient is pregnant, lactating or breast feeding 9. Any other disease or condition, which in the investigator’s medical opinion would preclude the patient’s participation in a clinical trial (e.g. recent MI, acute or chronic renal or liver failure) 10. Use of alemtuzumab (Campath®) within 9 months prior to Screen; anti-thymocyte globulin (ATG) or thymoglobulin within 3 months of Screen; or concurrent use of ≥ 0.3 mg/kg/day prednisone or equivalent as maintenance therapy (see Appendix 3) 11. Known hypersensitivity to oligonucleotides 12. Previous enrollment in an ALN-RSV01 study 13. Is employed or is a first-degree relative of anyone employed by Alnylam, a participating clinical trial site, to any Contract Research Organization (CRO) involved in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Treatment emergent AEs - Vital signs - Clinical laboratory and cytokine\CRP assessments - ECG parameters - Spirometry parameters - Pulse oximetry parameters - Physical exams (Complete and Directed) |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 20 |