Discordant Immunological Response in HIV Infected Subjects
Conditions
Keywords
mesenchymal stem cells, HIV Infection, discordant immunological response
Brief summary
Phase I/IIClinical trial, proof of concept, double blind, and placebo-controlled, randomized 2:1 (MSCs: placebo), total sample size is 15 subjects
Detailed description
This is a phase I-II, randomised, placebo-controlled, clinical trial, currently ongoing in a single Spanish hospital (Hospital Virgen del Rocío, Seville), to evaluate the safety and feasibility of a 4-doses treatment regimen with MSCs (1 million cells/Kg MSCs, weeks 0-4-8-20) in HIV infected adults with swith discordant virological and immunological response to antiretroviral therapy. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 15 days, receiving unblinded cell therapy. In the second phase of the trial, subjects are block randomised (1:1) to receive either MSCs (n=5), or placebo (n=5), as the control treatment. Immune response variables, adverse events, opportunistic infection signs are evaluated as determinants of safety and efficacy of MSCs. Study endpoints are measured along a follow-up period of 24 months, that includes 17 visits according to a decreasing frequency rate. Intention to treat, and per protocol, and safety analysis will be performed.
Interventions
DRUGInfusion of MSC
Intravenous infusion of 4 doses of adipose tissue derived allogeneic adult mesenchymal stem cells (1 million MSCs/Kg, weeks 0-4-8-20).
Infusion of placebo (weeks 0-4-8-20)
Sponsors
Iniciativa Andaluza en Terapias Avanzadas
Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Phase 1: uncontrolled, single arm biosafety evaluation (n=5) Phase 2: placebo-controlled, randomized, evaluation (n=10)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed HIV infection * Age\> 18 years, both sexes * In treatment with antiretroviral therapy (ART) * Sustained HIV viral load \<50 copies / ml for ≥ 1 years prior to study entry * CD4 + cell count \< 350/mL * Immunological discordant response defined as: an increase \<75 or \<150 in CD4+ cell counts within one or two years of undetectable viraemia, respectively; or CD4 + cell count \<350/mcl after 3 years of ART and undetectable viraemia (\<50 copies/ml) ≥ 1 year * Writen informed consent * In women of child bearing potential or her partners:commitment to use contraceptive method of proved efficiency throughout the duration of the clinical trial
Exclusion criteria
* Pregnancy, breastfeeding, or refusal to the use of contraceptive methods * Opportunistic infections in the last 12 months prior to study entry * Active co-infection with hepatitis B virus/hepatitis C virus * Child Pugh's scale stage C cirrhosis of the liver of any a aetiology * Portal hypertension and / or hypersplenism of any aetiology * Malignant neoplasia * Treatment with steroids, immunomodulators, interferon, chemotherapy or any other medicinal product that could modify the number of CD4+ within the last 12 months prior to study entry * Confirmed analytical 3 or 4 grade (AIDS Clinical Trials Group scale) abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse reactions | 24 months | Incidence of adverse reactions grade 3 and 4 according to DAIDs scale |
| Incidence of opportunist diseases | 24 months | — |
| Changes in CD4+ cell count and CD4+/CD8+ ratio | 28 days after the 4th infusion MSCs/placebo | Changes in CD4+ cell count and CD4+/CD8+ ratio as measured by flow citometry |
Secondary
| Measure | Time frame |
|---|---|
| T CD4 +/µl count evolution and CD4 +/CD8 + ratio throughout 48 weeks | 48 weeks |
Countries
Spain
Outcome results
None listed