A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Ability of CMX001 to Prevent or Control CMV Infection in R+ Hematopoietic Stem Cell Transplant Recipients

Inclusion Criteria:

1. Age ≥ 18 years. Males must be able and willing to use adequate contraceptive methods
throughout the treatment and follow-up phases of the study. Females must be
postmenopausal,surgically sterile or, for those female subjects of reproductive
potential, willing to agree to use 2 acceptable methods of birth control throughout
the treatment phase of the study, with at least one being a barrier method.

2. Allogeneic HSCT recipients who were CMV seropositive before transplantation (i.e., R+
patients).

3. Recipients who are less than 30 days post qualifying transplant. [Note: Under extreme
circumstances due to timing issues associated with logistics, patients may be
enrolled, i.e.receive first dose of study drug, up to Day 32 post-transplant. Sites
must first contact the Chimerix Medical Monitor to receive permission for FDD to be
Days 31 or 32 post-transplant.]

4. Recipients must have evidence of engraftment before randomization and receiving their
first dose of study drug. Evidence of engraftment will be defined as one of the
following:

- Absolute neutrophil count (ANC) increasing for 3 consecutive days with a count ≥
500 cells/mm3 by the third day OR

- Three (3) consecutive days with an ANC ≥ 500 cells/mm3. [Notes: For sites where
standard site practice is to monitor white blood count (WBC) early after
transplant as opposed to ANC, then engraftment will be defined as WBC increasing
for 3 consecutive days with an ANC ≥ 500 cell/mm3 on the third day. For
non-myeloablative or reduced-intensity transplants (i.e., mini-transplants)
where ANC does not fall below 500 cells/mm3, the site definition of engraftment
should be used.] Able to ingest and absorb oral medication (in the judgment of
the investigator and based on lack of significant GI events). [Note: Use of TPN
(total parenteral nutrition) is not in and of itself exclusionary as long as the
reason for use would not disqualify the patient based on this criterion.]

6. Willing and able to understand and provide written informed consent. 7. To the best of
his or her knowledge, willing and able to participate in all required study activities for
the duration of the study.

Exclusion Criteria:

1. Females who are pregnant or currently nursing.

2. Patients with a BMI > 35 kg/m2.

3. Patients with hypersensitivity to cidofovir or CMX001.

4. Recipients for whom the current, predose clinical course of CMV infection suggests
that the investigator would not be able to withhold treatment for CMV for a minimum
of 5, but preferably 7 days following the subject's first dose of study drug. [Note:
Patients who, with a high probability, will not be able to have their first efficacy
assessment because of CMV infection should not be enrolled into the study. That is,
investigators should not enroll recipients with increasing CMV viral loads predose
such that, in the PI's opinion, continuation along the same clinical course would
result in discontinuation (due to requirement for CMV treatment with a prohibited
medication) within the first week.]

5. Recipients who received any of the following:

• GCV, vGCV, foscarnet or CDV within 14 days prior to enrollment;

• any anti-CMV therapy following transplantation (including Cytogam®1),

- any CMV vaccine,

- any investigational drug with antiviral activity against dsDNA viruses within 14
days prior to enrollment, [Note: An investigational drug is defined as a drug
that is not approved for any indication by the FDA.]

- any other investigational drug (i.e., those without any "anti-dsDNA virus"
activity; for example, anti-influenza compounds) within 14 days prior to
enrollment without the prior written consent of the medical monitor.

Patients receiving high dose ACV (> 2000 mg total oral daily dose or > 5 mg/kg IV three
times daily) or vACV (Valtrex; > 3000 mg total daily dose) at the time of dosing. [Note:
These doses are for patients with normal renal function; patients who dose reduce on the
FDD are not excluded from the study.] 7. Patients with active CMV disease diagnosed within
6 months prior to enrollment; patients with CMV DNAemia requiring intervention with
antiviral therapy at the time of enrollment.

8. Patients who are HIV positive; patients with active HCV or HBV infection as evidenced
by plasma levels of HCV RNA or HBV DNA, respectively. [Note: Tests for viral
serology/infection performed prior to transplant and within 6 months of dosing may be used
to satisfy this criteria.] 9. HSCT recipients who, other than the qualifying HSCT,
received another allogeneic HSCT within the past 2 years. [Note: Patients who received one
or more autologous transplants in addition to the qualifying allogeneic HSCT are not
excluded from participation.] 10. Patients with renal insufficiency as evidenced by GFR <
30 mL/min. [Note: GFR will be calculated by the central laboratory using the MDRD study
formula.] 11. Patients with a current diagnosis of hypotony, uveitis, or retinitis or any
intraocular pathology that would predispose the patient to any one of these conditions.

12. Patients with hepatic dysfunction as evidenced by ALT or AST > 5 x ULN or direct
bilirubin > 2.5 x ULN. [Note: for these laboratory values, one retest is allowed per visit
(i.e.,screening or predose) at the central laboratory, local laboratory retest results may
be used at the discretion of the medical monitor.] 13. Patients with the following active
autoimmune disorders; myasthenia gravis, Addison's disease, Wegener's granulomatosis,
primary biliary cirrhosis, bullous pemphigoid, autoimmune hemolytic anemia, autoimmune
hepatitis, multiple sclerosis, Goodpasture's syndrome, idiopathic thrombocytopenic
purpura, lupus erythematosus, dermatomyositis, polymyositis, or vasculitis.

14. Patients with active solid tumor malignancies with the exception of basal cell
carcinoma or the condition under treatment (for example, lymphomas).

15. Patients who have had one or more episodes of hyperglycemic coma or diabetic
ketoacidosis within the past 6 months.

16. Patients with cardiovascular disease which, in the opinion of the investigator, would
interfere with the conduct of the study.

17. Patients with Grade 3 or 4 GVHD of the GI tract; patients with any GI disease that
would, in the judgment of the investigator, preclude the patient from taking or absorbing
oral medication (e.g. clinically active Crohn's disease, ischemic colitis, moderate or
severe ulcerative colitis, or any condition expected to require abdominal surgery during
the course of study participation).

18. Any other condition including abnormal laboratory values that would in the judgment of
the investigator put the subject at increased risk for participating in the trial, or
interferes with the conduct of the trial.