TITLE: Alnylam ALN-RSV01-106: A multi-center, randomized, double-blinded, placebo-controlled study to evaluate the safety and antiviral activity of aerosolized ALN-RSV01 plus standard of care in lung transplant patients infected with respiratory syncytial virus (RSV).

Why is this study being done? 
Patients who have had a lung transplant at Vanderbilt University Hospital in the past and now have symptoms which indicate that they may have an RSV (respiratory syncytial virus) infection. ALN RSV01 (the study drug) is an investigational drug that is being developed to treat RSV infection. All patients in this study will receive standard treatment for their infection and the study drug will be added to that treatment.

ALN RSV01 is a small interfering ribonucleic acid (siRNA). While DNA (deoxyribonucleic acid) is the substance in cells that contains our genes, RNA is the substance that cells use to produce proteins from those genes. A siRNA is made of 2 short man-made pieces of RNA that are attached together, and can reduce the amount of RNA made by a gene within cells. ALN RSV01 is thought to stop the RSV virus from reproducing in your lungs by reducing the amount of viral RNA in cells lining the lungs. The purpose of this study is to look at how safe the study drug is and how well patients are able to tolerate it. The study will also look at how inhaled ALN RSV01 affects RSV levels in the airway, and will measure the levels of ALN RSV01 in the blood. 

About 21 people who have received lung transplants and now have an RSV infection will take part in this study in the U.S.A. and Australia. We expect 6 patients to take part at Vanderbilt. Patients will be in this study for about 13 weeks (about 90 days).

Who is eligible to participate?
Minimum Age: 18
Maximum Age: 70

What is involved with this study?
After the Screening Visit which includes blood tests, chest X-ray, and nasal swabs, if the patient is eligible, then he/she will proceed to the next phase.

Administration of Study Drug Phase (Days 0, 1, 2)
• After review of all Screening tests, patients will be given either ALN RSV01 or placebo.
• Depending on the time of day the review of test results is done, patients may receive the first dose of ALN RSV01 or placebo that day or the next day. Dosing with ALN RSV01or placebo will be once per day for three days in a row..
• Patients will have a nasal swab taken each day and will be asked to provide a sputum sample each day (if able) for research.
• Patients will have a physical exam of certain body systems as well as a measure of blood pressure and pulse rate (how fast the heart is beating), and will be asked about changes in health status and changes in medication, all for research.
• Patients will have spirometry tests for research purposes.
• There will be pulse oximetry for research purposes.
• Blood and urine tests for routine safety tests for research, to measure blood levels of ALN RSV01, and to test for signs of inflammation. About 7 tablespoons of blood will be drawn each of these dosing days. We will try to draw blood from an existing intravenous (IV) line. If we are not able to draw blood from an IV line, we will need to draw blood from a needle in a vein. On Day 0, Day 1 and Day 2, blood will be drawn 10 times each day, once before getting the study drug, and the rest after taking the study drug for a period lasting up to 8 hours.
• Patients will be asked to complete a Patient Symptom Card each morning and afternoon (see sample attached).

Post Treatment Procedures (Day 3 to Day 6)
• Depending on patient health, they may either be able to go home or remain in the hospital. If able to go home, patients will be followed as an outpatient, and the visit schedule will be decided upon by the patient and the study doctor. Patients will need to be seen at least every other day and on Day 14. If remaining in the hospital, the procedures will be done every day except for the blood and urine, which will need to be done on Days 3 and 6 only.
• Patients will have a nasal swab taken each day and will be asked to provide a sputum sample each day (if able) for research.
• Patients will have a physical exam of certain body systems as well as a measure of blood pressure and pulse rate (how fast the heart is beating), and will be asked about changes in health status and changes in medication, all for research.
• Patients will have spirometry tests for research purposes.
• Patients will have pulse oximetry for research purposes.
• Blood and urine tests will be done for routine safety tests for research only on Days 3 and 6, when about 2 tablespoons of blood will be drawn per day.
• Patients may be a bronchoalveolar lavage (BAL), a test to wash a sample of cells from the lungs for testing. This will be done for research only once after treatment for research, if the doctor decides patient health will allow it to be done.
• Patients will be asked to complete a Patient Symptom Card each morning and afternoon for research.

Post Treatment Procedures (Days 7 thru 13)
Once patients leave the hospital, the procedures for these study visits will be done on the day of scheduled visits in the clinic. If remaining in the hospital, these procedures will be done every day (Days 7-13), unless noted otherwise.
• Patients will have a physical exam of certain body systems as well as a measure of blood pressure and pulse rate (how fast the heart is beating), and will be asked about changes in health status and changes in medication, all for research.
• Patients will have spirometry tests for research purposes (for outpatients, this will be done only on Day 14).
• Pulse oximetry will be done for research purposes.
• Patients will have a nasal swab taken and be asked to provide a sputum sample (if possible) for research.
• Patients will be asked for research purposes about changes in health status and medications.
• Patients will be asked to complete a Patient Symptom Card daily for research.

Post Treatment Procedures (Day 14)
Once patients leave the hospital, the procedures for this study visit will be done in the clinic.
• Patients will have a nasal swab and be asked to provide a sputum sample (if possible) for research.
• Blood and urine tests will be done for routine safety tests for research. About 2 teaspoons of blood will be drawn.
• Patients will have a physical exam as well as a measure of blood pressure and pulse rate (how fast the heart is beating), and will be asked about changes in health status and changes in medication, all for research.
• Patients will have spirometry tests for research purposes (for outpatients, this will be done only on Day 14).
• Pulse oximetry will be done for research purposes.
• Patients will have an ECG for research,
• Patients will be asked to complete a Patient Symptom Card for research.
• Patients will schedule the Day 30 Follow Up visit.

Follow Up Procedures (Day 30)
Patients will be evaluated in the clinic on Day 30.
• Patients will have a physical exam as well as a measure of blood pressure and pulse rate (how fast the heart is beating), and will be asked about changes in health status and changes in medication, all for research.
• Patients will have spirometry tests for research purposes.
• Pulse oximetry will be done for research purposes.
• Blood and urine tests for routine safety tests will be done for research. About 2 teaspoons of blood will be drawn at this visit.
• Patients will schedule the Day 90 Follow Up visit.

Follow Up Procedures (Day 90)
Patients will be evaluated in the clinic on Day 90.
• Patients will be asked for research purposes about changes in health status, and
• Patients will have spirometry tests for research purposes.