Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection

Peginterferon alfa-2 with ribavirin is the current standard of care for the treatment of HCV
infection; however, severe hematologic effects, including anemia, leukopenia, and
thrombocytopenia, may make this treatment less than ideal for patients with HCV. Medications
to prevent or treat serious neutropenia and anemia have been established and are commonly
used. However, thrombocytopenia remains a barrier to the effective treatment of HCV
infection in some patients. Developing a more effective treatment for thrombocytopenia for
these patients would decrease the risk of serious bleeding events. It may also improve HCV
treatment outcomes by preventing dose modifications or discontinuations of peginterferon
alfa-2 and ribavirin due to thrombocytopenia.

Anti-D is an antibody to the Rh (D) antigen on red blood cells. When anti-D attaches to the
Rh (D) antigen, immune-mediated destruction of platelets is prevented, helping to alleviate
low platelet levels in people with thrombocytopenia. This study will investigate the safety
and efficacy of anti-D for the treatment of thrombocytopenia in HCV patients currently on or
starting standard HCV treatment. Both HIV infected and uninfected participants will be
recruited for this study.

This study will last 12 weeks. Participants in this study must be either currently on
peginterferon alfa-2 and ribavirin treatment or initiating such treatment at the start of
the study; these two medications will not be provided by the study. At study entry,
participants will be given anti-D over a 30-minute infusion in an outpatient setting.
Participants will be observed for any adverse effects for 1 hour postinfusion. Some
participants may require additional doses of anti-D later in the study, depending on
individual response to the drug; participants may receive 1 to 6 doses of anti-D. Efficacy
of anti-D treatment will be assessed by absolute change in platelet count and the ability to
sustain plaletet counts greater than 50,000 cells/microL during the study. Cytokine levels
will also be monitored to gain insight on how anti-D may work with cytokines in platelet
survival and clearance.

Generally, study visits will occur at study entry and Weeks 1, 2, 4, 8, and 12. In patients
who require additional infusions of anti-D, there will be additional visits scheduled for
each additional infusion and a postinfusion visit occurring 1 week after each infusion. All
study visits will include medication history and blood collection. A clinical assessment and
a targeted physical exam will occur at study entry, Weeks 1 and 12, and at additional
infusion and postinfusion visits, if applicable.

Inclusion Criteria for All Participants:

- HCV-infected

- Currently on treatment for HCV OR plan to begin treatment for HCV at the start of
this study

- Platelet count less than 50,000 cells/microl

- Hemoglobin greater than 10 g/dl OR greater than 11 g/dl if peginterferon
treatment-naive

- Red blood cells are Rh (D) antigen-positive

- Negative Coombs direct antibody test

Inclusion Criteria for HIV Infected Group:

- HIV-infected

Inclusion Criteria for HIV Uninfected Group:

- HIV-uninfected

Exclusion Criteria:

- Prior treatment with intravenous immunoglobulin (IVIG), anti-D, or other medication
for the treatment of thrombocytopenia within 30 days of study entry

- Prior serious reaction to plasma products

- Absence of spleen

- Evidence of thrombotic thrombocytopenic purpura (TTP) OR cause of thrombocytopenia
other than HCV infection, HCV treatment, or HIV infection