E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000811 |
E.1.2 | Term | Acute infection with HIV |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate whether reactivation of HIV using immunoglobulin in individuals with AHI and virologically suppressed with ART, will reduce HIV viral reservoir at week 48. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
To investigate the effect of ART and immunoglobulin, at acute HIV infection on:
a. Immune activation
b. Gut permeability
c. Host gene expression
d. Clinical outcome
e. Immunological markers of T cell exhaustion
f. Inflammation
Tertiary Objectives:
To investigate the effect of using ART and immunoglobulin, at AHI on:
a. Host adaptive immune reponses
b. Low copy HIV RNA
c. Inflammation
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
(Titles, dates and version numbers of sub-studies are same as core trial: V2.0 18Jun12)
1. Gut Biopsy Sub-study
For those consenting to gut mucosal investigation, rectal biopsies will be taken at week 19 and week 24, with the option of an additional biopsy at week 48.
Objective:
To determine the effect of intravenous immunoglobulin at acute HIV infection on gut function.
2. Viral Rebound Sub-study
For those consenting to the viral rebound sub study, blood samples will be taken twice a week for 2 weeks then once a week for 2 weeks and a final test at week 60 (ie 7 extra visits over 12 weeks total)between wk48-60
Objective:
To determine the rate of viral rebound and the genetic sequence of the rebound virus upon stopping antiretroviral therapy.
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E.3 | Principal inclusion criteria |
1) Males and females aged between 18-65 years (inclusive).
2) HIV antibody negative with p24/PCR DNA positive
OR
HIV antibody positive with a previous HIV negative test in the preceding 3 months
OR
Health Protection Agency HIV incident virus assay (estimating virus acquired within 3 months)
3) Ability and willingness to provide informed consent
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E.4 | Principal exclusion criteria |
1) HIV negative
2) Pregnancy or lactating: at enrolment, randomisation or during study period as there is no data on IVIG in pregnant HIV+ women.
3) Patient unable or unwilling to comply with trial protocol
4) Known hypersensitivity to the active substances or to any of the excipients of the IMP
5) Current use or likely to require use of concomitant medication with known
interactions with HAART regimen in accordance with SmPCs.
6) Hep B sAg positive at screening or prior to starting antiretroviral therapy (ARV)
7) Documented active Hepatitis C.
8) Previous documented pulmonary embolism (PE), deep vein thrombosis (DVT), myocardial infarction (MI) or cerebrovascular accident (CVA)
9) Women of childbearing potential unwilling to use barrier method contraception (condoms)
10) Sexually active males with female partners of childbearing potential, unwilling to use barrier method contraception (condoms)
11) Insulin dependant diabetes
12) Documented bleeding disorders (for gut sub study participants only)
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in proviral DNA quantification between enrolment and week 48 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
between enrolment and W48 |
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E.5.2 | Secondary end point(s) |
Secondary Endpoints:
a. Changes in CD8 T-cell activation: the percentage of CD3+ CD8+ cells expressing CD38+
b. Gut permeability: 16S DNA
c. Host gene expression profiling
d. Clinical outcome: CD4 T-cell counts, CD4 T cell decline, HIV RNA
e. Immunological markers of T cell exhaustion: HLA-DR and PD-1
f. Inflammation (D-dimer)
Tertiary Endpoints:
a. Host adaptive immune responses: CD4 and CD8 HIV specific immune responses
b. Low copy HIV RNA
c. Inflammation (IL-6) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
between enrolment and W48 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No infusion of immunoglobulin |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |