HR# 20358 MUSC/Consent
MEDICAL UNIVERSITY OF SOUTH CAROLINA
CONSENT TO BE RESEARCH SUBJECTS
Protocol Title: A Phase 2, Multicenter, Double‑Blinded, Placebo‑Controlled, Multiple‑Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of VX‑809 Alone and in Combination with VX‑770 in Subjects with Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Protocol Number: VX09‑809-102, Version 3.0
Study Sponsor: Vertex Pharmaceuticals Incorporated
130 Waverly Street
Cambridge, Massachusetts 02139-4242 USA
Investigator: Patrick A. Flume, MD
Medical University of South Carolina
96 Jonathan Lucas St.
Charleston, SC 29485
Telephone: (843) 792-3199
24-hour telephone: (843) 792-2123
A. Purpose and Background
Introduction
You are being asked to take part in a research Study to look at an experimental treatment because you have been diagnosed with Cystic Fibrosis (CF) and have the F508del-CFTR gene mutation. CFTR's job is to move chloride across linings of the lung, skin, and other organs. In patients with CF, many health problems happen because CFTR is not working well. It is hoped that VX-770 and VX-809 can help CFTR work better in patients with CF.
The Study is paid for by Vertex Pharmaceuticals Incorporated (Vertex), who is the Sponsor of the Study.
Please read this Consent Form carefully. This form explains the things you will be asked to do before, during, and after the Study. If you decide that you would like to take part in the Study, you will be asked to sign this Consent Form. A copy of the signed Consent Form will be given to you to keep.
Taking part in the Study is voluntary. That means that you can decide not to take part. If you agree to take part, you can change your mind at any time without losing any benefits which you would have gotten if you were not in the Study. Your decision not to be in the Study will not affect the care that you would normally get from your doctor or benefits which you would have gotten if you weren’t in the Study. You can ask any questions about the Study at any time.
Purpose of the Study
Vertex is developing two drugs, VX-809 and VX-770, as a possible treatment for people with cystic fibrosis (CF). VX-809 and VX-770 are experimental drugs, which means that they have not been approved by the United States Food and Drug Administration (FDA), or by any other regulatory agencies for sale or use by the public.
This Study is being done to learn more about the safety, tolerability, how well you manage taking the drug, changes in drug concentration in your blood, and the effect of VX-809 when first given alone and then given in combination with VX-770 to patients with CF.
If you agree to participate, you will be one of about 198 subjects who are eighteen years of age or older, from up to 30 study sites in the United States and other countries around the world. The expected number of participants to be enrolled at the Medical University of South Carolina is 15. Dr. Patrick Flume will be the Principal Investigator (also called the “Study Doctor”) at the Medical University of South Carolina. Dr. Flume and MUSC will receive payment from the Sponsor for participating in the Study.
B. Procedures
This Study is in 3 parts, or “Cohorts”, and the informed consent is for your participation in Cohort 3. Most of the subjects in this Study will be homozygous for the F508del-CFTR gene mutation, but Cohort 2, which is now completed, also enrolled subjects who were heterozygous for the gene mutation. All subjects in Cohort 3 are homozygous for the F508del-CFTR gene mutation and will be enrolled in one of four different Treatment Groups (Treatment Group 1, 2, 3 or 4). Treatment Groups 1 and 2 must be completely enrolled before Treatment Groups 3 and 4 can begin enrolling subjects. Each Treatment Group will receive different doses of VX-809, VX-770, or placebo. The Study Drug in all Treatment Groups in Cohort 3 will be administered for 56 days. In this Consent Form we will refer to VX-809, the combination of VX-809 and VX-770, and placebo as the “Study Drug”.
Your entire participation could last for approximately 91 days (about 13 weeks). Your participation will include a screening period that will last up to 21 days, a treatment period that will last 56 days, and a follow-up visit 6 days after the final dose of Study Drug, as well as a follow‑up telephone call 14 days after the final dose of Study Drug.
This is a double-blinded, randomized, placebo controlled, multiple dose study:
Placebo-Controlled: This means that a placebo, which is a pill that looks just like the VX-809 or the VX-770 pills but does not contain any medicine, will be taken by some people in this Study. This is done so that the study findings can be looked at fairly.
Double- Blinded: This means that no one (you or the study site staff), will know whether you are taking VX-809 or the VX-809 placebo and the dose of VX-770 or VX-770 placebo. The Study Doctor can find out what treatment group you are in if it is necessary for your medical care.
Multiple Dose: This means that different subjects will receive more than one dose of Study Drug.
Randomized: This means that the choice of whether you will be given VX-809 and VX-770 or a placebo will be assigned by chance, like the flip of a coin. This means that the choice of whether you will be given VX-809 and VX-770 or a placebo will be assigned by chance, like the flip of a coin. Between the four treatment Groups in this Cohort, a total of 30 subjects will receive VX-809 and VX-770 and 8 will receive placebo. No one can choose what anyone receives.
Treatment Period
The diagram below describes the study’s treatment period. It represents the different treatment groups to which you could be randomized after completing the Screening period tests and checks. Your Study Doctor will discuss with you how and when to take the Study Drug.
Study treatment diagram
There are four (4) Treatment Groups (active or placebo) of different dose treatments in Cohort 3. Treatment Groups 1 and 2 (active or placebo) will receive doses of study drug to take every 12 hours and Treatment Groups 3 and 4 (active or placebo) will receive doses of study drug to take every 8 hours for the 56 days on the study. When you are enrolled you will be randomized to one of the four Treatment Groups.
If you are assigned to Treatment Group 1 or Group 2 in Cohort 3, twice a day you will receive either 2 VX-809 pills or VX‑809 matching placebo pills from Day 1 through 28, followed by 2 VX‑809 and 2 VX‑770 pills or VX-809 and VX-770 matching placebo pills from Day 29 through Day 56. If you are assigned to Treatment Group 3 or Group 4 in Cohort 3, three times a day you will receive 2 VX‑809 pills or VX-809 matching placebo pills from Day 1 through 28, followed by three times a day dosing with 2 VX‑809 and 3 VX‑770 or VX-809 and VX-770 matching placebo pills from Day 29 through Day 56.
The information from Treatment Groups 1 and 2 will be reviewed before enrollment in Treatment Groups 3 and 4 can begin.
On Day 56, you will receive only a morning dose of Study Drug. On the days when VX-770 is taken, Days 29-56, the doses of VX-770 should be taken at the same time as VX-809 is taken. Study Drug should be taken in the middle of a standard CF high fat, high calorie meal or snack throughout the Study. The meal or snack should be eaten within 30 minutes. You should take the Study Drug at the same times each day. Your doctor will further discuss with you how to take the Study Drug.
You will be given a supply of Study Drug at each visit, since you will take some of the Study Drug at home. You will be asked to fill out a Study Diary Card to record the dates, times, and amounts of the Study Drug you take as well as the timing of the meal or snack. You must bring all of the full, partially full and/or empty Study Drug packaging along with your Study Diary Card back to the clinic on each of your visits.
There are some Study requirements you must follow during the Study. Your Study Doctor and nurse will also review these with you:
Current CF medicines: You should stay on your current CF medicines.
· If you are taking inhaled tobramycin or other inhaled antibiotics continuously this should not change during the Study.
· If you are taking inhaled antibiotics that are being taken in a cycle (e.g. TOBI), this should not change during the Study. Inhaled antibiotics being taken in a cycle should be taken in a 28 day on/ 28 day off cycle. The Study Doctor will review this with you.
· If you are alternating 2 different antibiotics monthly, you should remain on the same schedule, synchronizing to the first dose of Study Drug as closely as possible.
· If you are taking Acetaminophen (paracetamol) for the treatment of minor pain, you should not take more than 1000 mg per dose and 4 doses per day of paracetamol.
Bronchodilators: If you are taking bronchodilators (short acting inhaled medicine), please do not take them the morning of the visits when you have Spirometry (a breathing test to see how well your lungs are working) testing (for Cohort 1 this will be at Screening, Day 1, 7, 14, 21, 22 and 27 and for Cohort 2 at Screening, Day 1, 14, 28, 42, 56, 57/58 and 62). If possible, you should not take your short acting inhaled medicine within 4 hours, long acting inhaled medicines within 12 hours and daily inhaled medicines within 24 hours of these visits. You will be given a bronchodilator diary to record the time and date of all bronchodilators taken within 24 hours of spirometry assessment.
Herbal medicines: There are certain herbal medications, like St. John’s Wort, that you must not take for 14 days before the first time you take the Study Drug and as long as you are participating in the Study. Please discuss all herbal medications you are taking with your study doctor.
Food and drink: You must not eat/drink grapefruit, grapefruit juice, marmalade or Seville oranges (also known as blood oranges) for 14 days before the first time you take the Study Drug and as long as you are participating in the Study. These foods contain substances that may interfere with how drugs can work.
Study Procedures
General Checks and Tests that will be done throughout the Study:
· Medical History: Questions will be asked about your health up to now, including allergies, illnesses, conditions, treatments, operations, general health, medicines, herbal and natural remedies.
· Concomitant Medications: You will be asked about any medicines that you are currently taking.
· Adverse Events: An adverse event is when something that happens to you, or something you experience, or is an abnormality in one of your laboratory tests, that is not typically expected. You will be asked how you are feeling and if you have had any changes to your health and well being since your last visit.
· Study Diary Card: You will be asked to fill this out at home detailing the times and dates when you take your Study Drug, as well as other general information regarding your use of the Study Drug. On the days before you will have a blood sample to test for Study Drug, you will also record the times that you eat your meals. You will also include other current medicines that you are taking and any adverse events.
· Physical Exam: You will have a complete physical exam in the Screening visit and which will include an exam of your overall body (head, neck, thyroid (a gland in your neck that helps regulate your metabolism); ears, eyes, nose, throat; lungs; heart; chest, lymph nodes (glands throughout your body that help fight infection); abdomen; skin; muscles and skeleton; nervous system). Your height and weight will be measured. Physical exams will not include looking at your reproductive organs. An abbreviated exam will be done at the Follow-up visit.
· Vital Signs: Your blood pressure, temperature, heart rate (beat), and respiratory (breathing) rate will be measured after you have been sitting for 5 minutes.
· Electrocardiogram (ECG, heart tracing): An ECG measures the electrical activity of your heart. You will be asked to lie down and small sticky pads like Band-Aids will be placed on your arms, legs, and across your chest. You will be asked to lie still for a few minutes and to hold your breath for a few seconds.
· Ambulatory ECG (Cohort 1 only): A small ECG machine (about the size of a digital camera) will record your heart tracing for 48 hours during the Screening period and for 24 hours during Day 14 and Day 21 visits. Small sticky pads will be placed on your chest that will connect to a small ECG recorder.
· Spirometry (Lung Function Test): Spirometry is a breathing test to see how well your lungs are working. This test is done by breathing into a tube connected to a machine that can measure airflow. You will be asked to take a deep breath and then blow out as hard and as long as possible for 3 tries. For study purposes you may not be provided the spirometry results while you are taking the Study Drug,
· Sweat Chloride Testing: Your sweat will be collected and sent to a lab for measurements. We will measure chemicals, such as salt, in your sweat. To collect the sweat, 2 sticky pads will be attached to the skin on your arm for 5 minutes. A gel-like medicine called pilocarpine is put on the pads and causes the sweat glands to produce more sweat. The pads stay on for about 5 minutes, then are removed and replaced by a disc to collect sweat for about 30 minutes. The entire procedure will then be repeated on your other arm.