Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 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. |
Drug: Anti-D
30-minute infusion administered in an outpatient setting
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Frequency and Severity of Adverse Events [Throughout study, for up to 12 weeks]
- Absolute Change in Platelet Count From Baseline [Through Week 12]
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New York Presbyterian Hospital (Cornell) | New York | New York | United States | 10021 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Principal Investigator: Kristen M. Marks, MD, Weill Medical College of Cornell University
Study Documents (Full-Text)
None provided.More Information
Publications
- K23AI065319-01
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Anti-D |
|---|---|
| Arm/Group Description | 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 |
| Period Title: Overall Study | |
| STARTED | 6 |
| COMPLETED | 6 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Anti-D |
|---|---|
| Arm/Group Description | 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 |
| Overall Participants | 6 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
51
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
16.7%
|
| Male |
5
83.3%
|
| Region of Enrollment (participants) [Number] | |
| United States |
6
100%
|
| Other baseline characteristics (Count of Participants) | |
| HIV coinfected |
1
16.7%
|
| Cirrhosis |
5
83.3%
|
| Decompensated Cirrhosis |
3
50%
|
Outcome Measures
| Title | Frequency and Severity of Adverse Events |
|---|---|
| Description | |
| Time Frame | Throughout study, for up to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Anti-D |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 6 |
| Any SAE |
3
50%
|
| Post infusion reactions |
2
33.3%
|
| Hepatic decompensation |
1
16.7%
|
| Any Hyperbilirubinemia |
6
100%
|
| Gr 3-4 Hyperbilrubinemia |
1
16.7%
|
| Anemia (all grade 1) |
5
83.3%
|
| Fatigue |
4
66.7%
|
| Fever |
2
33.3%
|
| Dyspnea on exertion |
3
50%
|
| Headache (all grade 1) |
2
33.3%
|
| Depression (mild) |
1
16.7%
|
| hypothyroidism |
1
16.7%
|
| Neutropenia (likely sec to IFN) |
4
66.7%
|
| Hospitalized |
3
50%
|
| Death |
1
16.7%
|
| Title | Absolute Change in Platelet Count From Baseline |
|---|---|
| Description | |
| Time Frame | Through Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Anti-D |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 6 |
| Platelet response >50,000/ul week 1 |
1
16.7%
|
| Platelet response >50,000/ul week 2 |
2
33.3%
|
| Platelet response >50,000/ul week 4 |
2
33.3%
|
| Platelet response >50,000/ul week 8 |
3
50%
|
| Platelet response >50,000/lu week 12 |
0
0%
|
| Tp-related dose interruption peginterferon/ribavir |
1
16.7%
|
| Anemia-related dose interruption peginterferon |
2
33.3%
|
| Anemia-related dose interruption ribavirin |
5
83.3%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Anti-D | |
| Arm/Group Description | 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 | |
All Cause Mortality |
||
| Anti-D | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Anti-D | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | |
| Gastrointestinal disorders | ||
| Gastroenteritis | 1/6 (16.7%) | 1 |
| Hepatobiliary disorders | ||
| Hepatic decompensation | 1/6 (16.7%) | 1 |
| Infections and infestations | ||
| Death (sepsis_ | 1/6 (16.7%) | 1 |
| Nervous system disorders | ||
| Seixzure/meningitis | 1/6 (16.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Anti-D | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | |
| Blood and lymphatic system disorders | ||
| Anemia Gr 1 | 5/6 (83.3%) | 5 |
| Cardiac disorders | ||
| Dyspnea on exertion | 3/6 (50%) | 3 |
| Endocrine disorders | ||
| Hypothyroidism | 1/6 (16.7%) | 1 |
| Hepatobiliary disorders | ||
| Hyperbilirubinemia Gr 3-4 | 1/6 (16.7%) | 1 |
| Nervous system disorders | ||
| Headache | 1/6 (16.7%) | 1 |
| Vascular disorders | ||
| Post infusion reactions | 2/6 (33.3%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Kristen Marks |
|---|---|
| Organization | Weill Cornell |
| Phone | 212-746-4177 |
| markskr@med.cornell.edu |
- K23AI065319-01