Ledipasvir/Sofosbuvir Treatment for Hepatitis C in HCT Recipients.

This is an open-label observational/ feasibility study to treat candidates for HCT infected
with hepatitis C prior to the transplantation to reduce the complications associated with
hepatitis C in the post-transplant setting.

The study will be conducted at Kaiser Permanente Los Angeles Medical Center and City of Hope
National Medical Center, Duarte, CA.

There is no data available on the outcomes of treating hepatitis C with DAA's pre-HCT in
candidates with hepatitis C infection. The ASBMT task force made recommendation to consider
treating hepatitis C infection pre-HCT based on potential benefits it may be associated with.
A single case report has documented benefit of treating a donor infected with hepatitis C
prior to stem cell collection with DAA and ribavirin

Subject Population will include autologous or allogeneic HCT candidates (for hematologic
malignancy) who have hepatitis C infection. Subjects will be considered treatment-experienced
if they have received prior interferon-based therapy. Treatment-experienced patients with
prior use of DAA(s) are excluded from study participation.

This study will treat HCV patients prior to HCT, with the goal of reducing early post HCT
complications in the first 100 days post HCT followed by measuring outcomes at 2 years post
HCT.

Subjects will receive LDV 90mg/SOF 400mg FDC for 12 weeks.

Inclusion Criteria:

1. Participant must be male or female at least 18 years of age at time of screening

2. Participant must be able to provide written Informed Consent

3. Participant must be able to adhere to study visit/procedure schedule and protocol
requirements

4. Time available (at least 12 weeks) for treatment of hepatitis C prior to autologous or
allogeneic transplantation

5. First autologous or allogeneic HCT and hematologic disease in remission on initiation
of antiviral therapy for hepatitis C infection

6. Patients with myelodysplastic syndrome, aplastic anemia or hemoglobinopathies will be
eligible to participate regardless of disease status if plan is to proceed to HCT

7. Female participant without childbearing potential must meet at least one of the
following:

- Postmenopausal defined as women >54 years of age with amenorrhea for ≥ 2 years
prior to screening

- Surgically sterile defined as bilateral tubal ligation or bilateral oophorectomy
or hysterectomy

- Has male sexual partner with vasectomy

8. Female participant of childbearing potential must meet at least one of the following:

- Must be using at least 1 effective contraceptive method at screening and agree to
practice 2 effective contraceptive methods1 for study duration, starting
Screening through 30 days after stopping study drug

- Practice total abstinence from sexual intercourse (minimum 1 complete menstrual
cycle)

- Sexually active with female partner only

9. Male participant who is not surgically sterile and is sexually active with female
partner of childbearing potential must agree to practice 2 effective contraceptive
methods1 for study duration, starting at Screening through 30 days after stopping
study drug

10. Participant must have the following indicator- of chronic hepatitis C virus infection
prior to study enrollment:

• Positive for HCV RNA at the time of screening

11. Participant screening laboratory result must indicate HCV genotype 1, 4, 5 or
6-infection if historical result is not available.

Exclusion Criteria:

1. Participant unwilling to provide written informed consent

2. Participant unwilling to adhere to study visit/procedure schedule and protocol
requirements

3. Participant is pregnant or is a breastfeeding female

4. Positive test result for hepatitis B surface antigen (HBsAG), hepatitis B core
antibody (HBcAb), or confirmed positive anti-HIV antibody test

5. Received study contraindicated medications prior to study drug administration
including but not limited to those listed in the Full Prescribing Information Sheet
for ledipasvir/sofosbuvir (Harvoni®).

6. Clinically significant abnormalities or co-morbidities, other than HCV infection that
in opinion of the investigator makes subject unsuitable for this study or drug regimen

7. Prior or current use of any investigational or commercially available anti-HCV agents
other than interferon or ribavirin or receipt of any investigational product within 6
weeks prior to study drug administration

8. Prior treatment of chronic HCV infection with a direct acting antiviral agent(s):
telaprevir, boceprevir, sofosbuvir, simeprevir, or other direct acting antiviral

9. History of solid organ transplant

10. Screening laboratory analyses shows any of the following abnormal laboratory results:

Estimated Glomerular filtration (eGFR) rate < 30 mL/min

11. Evidence of cirrhosis, documented by one of the following:

Liver biopsy histologic diagnosis: Metavir Score greater than 3 (includes 3 - 4 or ¾)
or Ishak score greater than 4 In the absence of liver biopsy: a FibroScan score
greater than or equal to 12.5 kPa or Fibrotest score of >0.75 AND an APRI score
greater than 1.5

12. History of liver decompensation: ascites noted on a physical exam, imaging or other
test; variceal bleeding; hepatic encephalopathy

13. Confirmed presence of hepatocellular carcinoma indicated on computed tomography,
magnetic resonance, or other imaging techniques within 3 months prior to screening

14. HCV genotype performed during screening indicates infection with genotype 2 or 3

15. Recent history of drug or alcohol abuse that could, in the opinion of the
investigator, affect adherence to the study protocol