Hepatitis C, HIV Infections, Thrombocytopenia
Conditions
Keywords
HIV, HCV, Hepatitis C, Thrombocytopenia
Brief summary
Thrombocytopenia occurs when a person's blood has a decreased number of platelets, which are cells involved in blood clotting. This condition may lead to uncontrolled bleeding and can be fatal. Thrombocytopenia commonly occurs with hepatitis C virus (HCV) infection or as a result of standard HCV treatment. Anti-D is an antibody approved by the Food and Drug Administration (FDA) for the treatment of HIV-related thrombocytopenia. The purpose of this study is to determine the safety and effectiveness of intravenous anti-D for the treatment of thrombocytopenia in patients with HCV infection who are starting or already undergoing treatment with peginterferon alfa-2 and ribavirin. This study will recruit HCV patients both with and without HIV co-infection.
Detailed description
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.
Interventions
DRUGAnti-D
30-minute infusion administered in an outpatient setting
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and Severity of Adverse Events | Throughout study, for up to 12 weeks |
| Absolute Change in Platelet Count From Baseline | Through Week 12 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anti-D Participants will be given anti-D 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.
Anti-D: 30-minute infusion administered in an outpatient setting | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Anti-D |
|---|---|
| Age, Continuous | 51 years |
| Other baseline characteristics Cirrhosis | 5 Participants |
| Other baseline characteristics Decompensated Cirrhosis | 3 Participants |
| Other baseline characteristics HIV coinfected | 1 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 3 / 6 |
Outcome results
Primary
Absolute Change in Platelet Count From Baseline
Time frame: Through Week 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anti-D | Absolute Change in Platelet Count From Baseline | Platelet response >50,000/ul week 1 | 1 Participants |
| Anti-D | Absolute Change in Platelet Count From Baseline | Platelet response >50,000/ul week 2 | 2 Participants |
| Anti-D | Absolute Change in Platelet Count From Baseline | Platelet response >50,000/ul week 4 | 2 Participants |
| Anti-D | Absolute Change in Platelet Count From Baseline | Platelet response >50,000/ul week 8 | 3 Participants |
| Anti-D | Absolute Change in Platelet Count From Baseline | Platelet response >50,000/lu week 12 | 0 Participants |
| Anti-D | Absolute Change in Platelet Count From Baseline | Tp-related dose interruption peginterferon/ribavir | 1 Participants |
| Anti-D | Absolute Change in Platelet Count From Baseline | Anemia-related dose interruption peginterferon | 2 Participants |
| Anti-D | Absolute Change in Platelet Count From Baseline | Anemia-related dose interruption ribavirin | 5 Participants |
Primary
Frequency and Severity of Adverse Events
Time frame: Throughout study, for up to 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anti-D | Frequency and Severity of Adverse Events | Any SAE | 3 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Post infusion reactions | 2 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Hepatic decompensation | 1 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Any Hyperbilirubinemia | 6 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Gr 3-4 Hyperbilrubinemia | 1 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Depression (mild) | 1 Participants |
| Anti-D | Frequency and Severity of Adverse Events | hypothyroidism | 1 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Neutropenia (likely sec to IFN) | 4 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Hospitalized | 3 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Death | 1 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Anemia (all grade 1) | 5 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Fatigue | 4 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Fever | 2 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Dyspnea on exertion | 3 Participants |
| Anti-D | Frequency and Severity of Adverse Events | Headache (all grade 1) | 2 Participants |