| Eligibility |
Inclusion Criteria:
For inclusion into the trial, subjects were required to fulfill all of the following
criteria:
1. Aged between 18 to 75 years, inclusive. Males must have been able and willing to use
adequate contraceptive methods throughout the study and for 3 months after the final
dose. Females must have been post-menopausal, surgically sterile, or willing to use
adequate contraception for the duration of the study (screening through the Day 48
visit).
2. Were renal or hematopoietic stem cell transplant patients who met the following
criteria:
1. Renal transplant patients who:
- Were at least 28 days post transplant;
- Were in stable condition with hemoglobin >10 g/100 mL;
- Had no evidence of graft rejection (i.e., serum creatinine was not
increasing [±30%], creatinine clearance was not decreasing);
- Were on a stable immunosuppressant regimen for at least 14 days prior to
dosing.
- Had either urine levels of BK virus DNA =10^4 copies/mL without viremia or
plasma levels of BK virus DNA <10^4 copies/mL (with or without viruria).
2. Stem cell transplant patients who:
- Were a minimum of 3 days post documentation of successful engraftment as
evidenced by an absolute neutrophil count >500 cells/mm3;
- Had urine levels of BKV =10^4 copies/mL.
3. Had GFR >30 mL/min.
4. Were able to swallow tablets.
5. Were willing and able to understand and provide written informed consent.
6. Were willing and able to participate in all required study activities for the duration
of the study (including ingestion of oral medication).
Exclusion Criteria
Any of the following was regarded as a criterion for exclusion from the trial:
1. Females who were currently nursing or pregnant.
2. Were using illicit drugs or abusing alcohol.
3. Had hypersensitivity to cidofovir or brincidofovir.
4. Had received aminoglycosides (intravenously) or NSAIDS (except as given for
cardioprotective treatment) within 7 days prior to enrollment; had received
leflunomide, cidofovir, or any other medication for treatment of BK virus infection or
disease within 14 days prior to enrollment; had received any investigational drug
(including maribavir) within 30 days prior to enrollment.
5. Were HIV positive (results must have been obtained within 1 year prior to dosing); had
active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by
plasma levels of HCV RNA or HBV DNA, respectively.
6. Were renal transplant patients with evidence of biopsy proven acute rejection in the 3
weeks prior to enrollment. This exclusion criterion applied only to those patients for
whom a biopsy was performed within the 3 weeks prior to enrollment.
7. Were stem cell transplant patients who:
1. Had cystitis =Grade 3 National Cancer Institute, Common Terminology Criteria for
Adverse Events version 3.0.
2. Had Grade 3 or 4 graft versus host disease (GVHD).
3. Had untreated or uncontrolled Grade 2 GVHD.
4. Had received ganciclovir or valganciclovir within 14 days prior to enrollment.
8. Had mucositis that prevented ingestion of oral medication.
9. Had hypotony, uveitis, or retinitis or any intraocular pathology that would have
predisposed the patient to any one of these conditions.
10. Had unstable or poorly controlled diabetes, defined as having frequent hypoglycemic
and/or hyperglycemic events on a daily basis (brittle diabetes), with fluctuating
short acting insulin requirements daily, or requiring unpredictable insulin
supplementation to oral hypoglycemic agents on a regular basis.
11. Had bilirubin >2.5 x the upper limit of normal.
12. Had cardiovascular disease which, in the opinion of the investigator, would have
interfered with the conduct of the study.
13. Had any of the following autoimmune diseases: Addison's disease, autoimmune hemolytic
anemia, autoimmune hepatitis, bullous pemphigoid, celiac disease, dermatomyositis,
active Goodpasture's syndrome, idiopathic thrombocytopenic purpura, active lupus
erythematosus, multiple sclerosis, myasthenia gravis, pemphigus vulgaris,
polymyositis, primary biliary cirrhosis, vasculitis, Wegener's granulomatosis.
14. Had active malignancies (with the exception of basal cell carcinoma or the condition
under treatment for hematopoietic stem cell transplant patients).
15. Had concurrent or ongoing =Grade 2 gastrointestinal symptoms including nausea,
vomiting, diarrhea, constipation, or gastroenteritis. Patients with active
gastrointestinal disease including inflammatory bowel disease, irritable bowel
syndrome, or celiac sprue.
16. Had any other condition including abnormal laboratory values that would have, in the
judgement of the investigator, put the subject at increased risk for participating in
the trial, or interfered with the conduct of the trial.
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