Treatment With MSC in HIV-infected Patients With Controlled Viremia and Immunological Discordant Response

Study Overview
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Brief Summary
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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
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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.

Official Title
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Clinical Trial Phase I/II, of Test of Concept, Blind Double, Randomized, Controlled With Placebo, to Assess the Safety and Efficiency of the Treatment With Allogenic Adult Mesenchymal Stem Cells From Adipose Tissue Expanded, in HIV-infected Patients With Controlled Viremia and Immunological Discordant Response

Conditions
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Discordant Immunological Response in HIV Infected Subjects

Intervention / Treatment
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* Drug: Infusion of MSC
* Drug: Infusion of placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 1: uncontrolled, single arm biosafety evaluation (n=5) Phase 2: placebo-controlled, randomized, evaluation (n=10)
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal stem cells<br>Intravenous infusion of 4 doses of allogenic adult mesenchymal stem cells from adipose tissue | Drug: Infusion of MSC<br>* Intravenous infusion of 4 doses of adipose tissue derived allogeneic adult mesenchymal stem cells (1 million MSCs/Kg, weeks 0-4-8-20).<br>|
| Placebo Comparator: Placebo<br>Intravenous infusion of 4 doses of Placebo | Drug: Infusion of placebo<br>* Infusion of placebo (weeks 0-4-8-20)<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse reactions | Incidence of adverse reactions grade 3 and 4 according to DAIDs scale | 24 months | 
| Incidence of opportunist diseases |  | 24 months | 
| Changes in CD4+ cell count and CD4+/CD8+ ratio | Changes in CD4+ cell count and CD4+/CD8+ ratio as measured by flow citometry | 28 days after the 4th infusion MSCs/placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T CD4 +/µl count evolution and CD4 +/CD8 + ratio throughout 48 weeks |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mesenchymal stem cells, HIV Infection, discordant immunological response