Clinical trial NCT02290041: Treatment With MSC in HIV-infected Patients With Controlled Viremia and Immunological Discordant Response
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Discordant Immunological Response in HIV Infected Subjects
Keywords: mesenchymal stem cells
HIV Infection
discordant immunological response
Lead sponsor: Andalusian Network for Design and Translation of Advanced Therapies
Sponsor class: OTHER
Collaborators: name: Iniciativa Andaluza en Terapias Avanzadas
First posted: 2014-11-13
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1: uncontrolled, single arm biosafety evaluation (n=5) Phase 2: placebo-controlled, randomized, evaluation (n=10)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse reactions
timeFrame: 24 months
measure: Incidence of opportunist diseases
timeFrame: 24 months
measure: Changes in CD4+ cell count and CD4+/CD8+ ratio
timeFrame: 28 days after the 4th infusion MSCs/placebo
Secondary outcomes:
measure: T CD4 +/µl count evolution and CD4 +/CD8 + ratio throughout 48 weeks
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Seville
country: Spain
facility: Virgen del Rocío University Hospital
Study officials:
affiliation: Hospitales Universitarios Virgen del Rocío
name: Luis F. López Cortés, MD
role: STUDY_CHAIR
References:
citation: Trujillo-Rodriguez M, Viciana P, Rivas-Jeremias I, Alvarez-Rios AI, Ruiz-Garcia A, Espinosa-Ibanez O, Arias-Santiago S, Martinez-Atienza J, Mata R, Fernandez-Lopez O, Ruiz-Mateos E, Gutierrez-Valencia A, Lopez-Cortes LF. Mesenchymal stromal cells in human immunodeficiency virus-infected patients with discordant immune response: Early results of a phase I/II clinical trial. Stem Cells Transl Med. 2021 Apr;10(4):534-541. doi: 10.1002/sctm.20-0213. Epub 2020 Dec 2.