A Study of the Efficacy and Safety of VX-150 in Subjects With Osteoarthritis of the Knee

Inclusion Criteria:

- Willing and able to comply with scheduled visits, treatment plan, study restrictions,
laboratory tests, contraceptive guidelines, and other study procedures.

- Subjects (male and female [of non-childbearing potential]) will be between the ages
of 40 and 80 years, inclusive. Female subjects must have a negative pregnancy test at
Screening and on Day 1 of each Treatment Period and must not be nursing; male
subjects must not have a female partner who is pregnant or nursing.

- Body mass index (BMI) of 18.0 to 38.0 kg/m2, inclusive, and a total body weight of 50
to 150 kg.

- Ambulatory with osteoarthritis of the knee with symptoms for at least 6 months and
pain on the majority of days for the past 30 days. Symptoms must include knee joint
pain. In subjects with bilateral knee osteoarthritis, the more symptomatic knee will
be considered the index knee.

- Radiographic evidence of at least one tibiofemoral osteophyte in the index knee
within 12 months before the Day 1 Visit.

- WOMAC pain subscale score

Exclusion Criteria:

- History in the past 10 years of reactive arthritis, rheumatoid arthritis, psoriatic
arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel
disease, sarcoidosis, amyloidosis or fibromyalgia.

- History in the past 10 years of malignancy with the exception of resected basal cell
carcinoma, squamous cell carcinoma of the skin or resected cervical atypia or
carcinoma in situ.

- History of cardiac dysrhythmias requiring anti-arrythmia treatment(s).

- History of abnormal laboratory results ≥2.5 × upper limit of normal (ULN) indicative
of any significant medical disease which in the opinion of the investigator would
preclude the subjects participation in the study.

- A known or clinically suspected infection with human immunodeficiency virus or
hepatitis B or C viruses.

- Other serious, acute or chronic medical or psychiatric illness that in the judgment
of the investigator could compromise subject safety, limit the subject's ability to
complete the study and/or compromise the objectives of the study.

- Either participated within 3 months in another investigational study in which the
subject was exposed to study drugs or vaccines,or will participate concurrently in
such study.

- History of drug or alcohol dependence in the past 3 years, or a positive test for
drugs of abuse at the Screening Visit.

- Requires opioids for pain relief.

- Changed analgesic treatment regimen within 30 days of the Screening Visit.

- Received or plan to receive short acting hyaluronic acid, corticosteroid, or other
intra-articular injections as follows:

1. in the index knee within 3 months of the Screening Visit, or at any time during
the study

2. in any other joint within 4 weeks of the Screening Visit, or at any time during
the study

- Received or plan to receive long acting hyaluronic acid or other intra-articular
injections as follows:

1. in the index knee within 6 months of the Screening Visit, or at any time during
the study

2. in any other joint within 4 weeks of the Screening Visit, or at any time during
the study

- History of arthroscopic or open surgery within 12 months before the Screening Visit,
or have a planned surgery during, or immediately after, study follow-up.

- History of joint replacement surgery in the index knee.

- Significant hip pain, ipsilateral to the index knee that may interfere with
assessments of index knee pain.

- Clinical signs and symptoms of an active knee infection.

- Current use of a handicap assistance device (unilateral assistance device such as a
cane is permitted).

- Started a new physical therapy, weight loss, or exercise program within 3 months of
the Screening Visit, or are not willing to maintain a stable program during the
course of the study.

- Lab abnormalities at the screening visit.