Study of the Effectiveness of Passive Immunotherapy in HIV-Infected Patients Who Are in Virologic Failure

HIV Infection Clinical Trial

Official title:

Passive Immunotherapy in HIV-Infected Patients Who Fail to Respond to Multiple Highly Active Antiretroviral Treatment. Randomized Study in Two Phases.

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT00353327
• Other study ID #: PIT-01
• Status: Suspended
• Phase: Phase 2/Phase 3
• First received: July 17, 2006
• Last updated: March 28, 2008
• Start date: October 2006

Study information

• Verified date: March 2008
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

To study the effect of passive immunotherapy (PIT) over the HIV-viral load and the CD4 T+-cell counts in patients who have failed to respond to three different Highly-Active Antiretroviral Therapy (HAART), and who have at the moment less than 100 CD4+-T cells/ml and a viral load over 20,000 copies/ml.

Description:

Double blind comparative randomized study with placebo in two phases:

Phase I: I: A pilot study to asses the virologic efficacy in 30 patients will be done. They will be under the same HAART regimen, and they will be randomized to receive:

1. Group I: HAART + PIT (n= 15)

2. Group II: HAART + placebo (non-hyperimmune plasma) (n= 15)

Passive immunotherapy will consist in 500 cc of inactivated plasma with methylene-blue (standard inactivation method) from asymptomatic patients in early phases of the infection. A transfusion will be done, and a complete blood test including viral load and CD4+-T cell counts will be done at days 3, 7, 14, 21 and 28. The non-hyperimmune plasma (Group II) will be inactivated by the same method.

A second dose of hyperimmune plasma and placebo (Group I and Group II respectively) will be administered at +1 month from the beginning of the trial.

A complete blood test including viral load and CD4+-T cell counts will be done at month +2, +3 and +4.

Phase II: 30 patients under the same HAART regimen will be randomized to receive:

1. Group I: HAART + PIT (n= 15)

2. Group II: HAART + placebo (non-hyperimmune plasma) (n= 15)

Passive immunotherapy will consist in 500 cc of inactivated plasma with methylene-blue (standard inactivation method) from asymptomatic patients in early phases of the infection, guided by the neutralization capacity of the plasma donors over the virus' receptor . A transfusion will be done, and a complete blood test including viral load and CD4+-T cell counts will be done at days 3, 7, 14, 21 and 28. The non-hyperimmune plasma (Group II) will be inactivated by the same method.

A second dose of hyperimmune plasma and placebo (Group I and Group II respectively) will be administered at +1 month from the beginning of the phase II.

The patients will remain under HAART the next year. A complete clinical examination, and a blood test that includes hemogram and biochemical parameters (renal and hepatic function), and viral load will be done each month. Every three months, a CD4+/CD8+ T cell count will be done, and it will be obtained plasma and serum from each patient.

Additionally, a genotype and a virtual phenotype of the HIV will be obtained at the beginning and at the end of the study.

Study end-points:

-Main end-point: Phase I: proportion of patients who reduce their plasma viral load > or = 1 log after two infusions of hyperimmune plasma.

Phase II: proportion of patients who reduce their plasma viral load > or = 1 log after a year.

• Secondary end-points:

1. Proportion of patients whose CD4+ T cell count is over 100 cells/mm3 after a year.

2. Proportion of patients whose p24-antigenemia is below the limits of detection.

3. Number of mutations conferring resistance to antiretrovirals at the end of the study compared to the mutations at the beginning.

4. Type C events.

5. Death.

6. Toxicity.

7. Adherence.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 30
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-1 infected patients (CDC C category) confirmed by a Western-blot

• CD4 T cell count under 100/ml form 6 months before the inclusion, and who have never been over 600 CD4 T cells/ml in the last 6 months, even if they have been receiving HAART.

• The patients have received at least 3 different HAART regimens, and they have failed to respond (define failure: CD4 T cell count under 100/ml and plasma viral load over 20,000 copies/ml).

• Plasma viral load over 20,000 copies/ml during at least 6 months.

• Written informed consent

• 18 years old or older

Exclusion Criteria:

• Asymptomatic patients who fill the A category of the CDC (1993)

• Younger than 18 years old

• Who are not expected to accomplish the treatment or the follow up visits

• Pregnancy, breast-feeding women, or women who want to get pregnant

• Denied consent

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

Intervention

Procedure:
• Plasma infusion

Locations

Country	Name	City	State
Spain	Hospital Clínic Barcelona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lowering of plasma viral load after the first plasma infusion
Primary	Lowering of plasma viral load after a year
Secondary	Elevation of CD4 T cell count
Secondary	Negativation of p24 HIV antigen
Secondary	HIV RNA mutations conferring resistance to HAART
Secondary	Development of C-events
Secondary	Dead
Secondary	Toxicity
Secondary	Accomplishment