Harvoni Treatment Porphyria Cutanea Tarda

This is a clinical trial, which means its purpose is to study an intervention or treatment.
In this study all patients with PCT will be given a standard dose of Harvoni and monitored
for two years. Currently there are two standard therapies for PCT, phlebotomies (removing
certain amounts of blood at specific intervals), or low dose hydroxychloroquine (an oral
pill). These treatments are used for patients with PCT whether or not they also have HCV. For
patients with HCV however, we do not know whether treating the HCV first will also resolve
the PCT symptoms. There will be an initial visit to determine whether participants are
eligible to be in the study. If a participant is found to be eligible, he/she will be asked
come to the study site once every month over the course of one year, and then once every 3
months for an additional year. There will be approximately 17 visits over the course of the
whole study. At these visits the study doctors will check in with the participant and some
blood and urine samples will be taken. Participants will not be charged for any of the lab
tests that are being done as a part of this study alone. All participants in this study will
receive the Harvoni pills at no cost to them.

Inclusion Criteria

1. Willing and able to give informed consent

2. ≥18 years of age

3. Symptoms and signs consistent with PCT and well documented biochemical diagnosis
(urinary total porphyrin excretion > 800 mcg/g Creatinine with HPLC pattern typical of
PCT—predominance of 8- and 7-carboxyl porphyrins)

4. Clinical diagnosis of PCT established by a study PI

5. Chronic hepatitis C: HCV RNA positive and quantifiable in serum detected within 90
days of enrollment, and documented HCV genotypes 1,4, 5, or 6 for which Harvoni is an
approved therapy.

6. Women of child-bearing potential must be willing to avoid pregnancy and use an
accepted and effective contraceptive method during treatment.

Exclusion Criteria

1. Women who are pregnant or who are breast-feeding

2. Patients who have already started treatment of PCT with phlebotomy or low dose
hydroxychloroquine or chloroquine, or who have been in such treatment in the past 30
days

3. Patients who have already started another treatment regimen for CHC, or who have taken
such treatment in the past 30 days

4. Subjects who are enrolled in PC7206

5. HIV infection with CD4 counts at baseline less than 350/µL or with evidence of any
active AIDS-defining illnesses

6. Ongoing active alcohol abuse, defined as a history of drinking more than 25 drinks of
alcohol per week during most weeks in the prior 4 months (History of prior, but not
current alcohol abuse will NOT be grounds for exclusion because we seek to treat
subjects with PCT and CHC of the type typically seen in clinical practice)

7. Any ongoing active IV drug use

8. Patients who are taking amiodarone or who have taken amiodarone within 60 days prior
to enrollment

9. Patients who are taking, or within the prior 28 days have taken, rifampicin or St
John's wort (Hypericum perforatum), both of which are P-gp inducers, which may
significantly reduce the drug levels and therapeutic effects of Harvoni

10. Uncontrolled diabetes (HbG A1c >9.5% within 60 days prior to enrollment)

11. Chronic hepatitis B

12. Autoimmune hepatic liver injury—autoimmune hepatitis, primary biliary
cholangitis/sclerosing cholangitis or overlap syndrome

13. Alcoholic hepatitis

14. Other metabolic disorders of the liver, e.g. Alpha 1 antitrypsin deficiency with ZZ Pi
type, Wilson's disease

15. Prior known or suspected drug-induced liver injury within 6 months of enrollment

16. Known or suspected hepatocellular carcinoma

17. On liver transplant list, or current MELD >12

18. History of liver transplant

19. Estimated GFR (Creatinine clearance) <30 mL/min (per Sofosbuvir being cleared by the
kidney)

20. Serum ALT or AST >10x normal

21. Serum bilirubin >2 mg/dL (excluding patients with known or suspected Gilbert's
syndrome)

22. Any other comorbid condition, which in the opinion of the investigator precludes
participation