Study on Interleukin-7 (CYT107) in HIV Patients (Inspire 2)
This study was designed to evaluate the pharmacokinetics of 20µg/kg/week of Interleukin-7 (CYT107), the biological activity and safety of repeated cycles of CYT107, for a maximum of 4 cycles within 21 months and a maximum of 3 cycles within 12 months.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Multicenter Study of Subcutaneous Intermittent Recombinant Interleukin-7 (CYT107) in Chronically HIV-infected Patients With CD4 T-lymphocyte Counts Between 101-400 Cells/mm3 and Plasma HIV RNA< 50 Copies/mL After at Least 12 Months of HAART|
- • To study, in all included patients, the biological activity and safety of repeated cycles of CYT107, for a maximum of 4 cycles within 21 months and a maximum of 3 cycles within 12 months. [ Time Frame: 2 years (24 months) ] [ Designated as safety issue: Yes ]
- • To characterize in the first 12 patients, PK and PD of CYT107 . • To further characterize in all included patients, the safety profile established with CYT107 at 20 µg/kg including monitoring of HIV RNA and immunogenicity. • • • [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To characterize in the first 12 patients, PK and PD of CYT107 .
- To further characterize, the safety profile established with CYT107 at 20 µg/kg including monitoring of HIV RNA and immunogenicity.
- To further examine CYT107 effect on HIV specific T-cells.
- To document other properties of IL-7, (ie: T-cell homing within the GI tract).
To assess the sustained CD4 increase until the end of the two years
- the safety of CYT107 treatment over the same period
- the potential effect of the CYT107 induced immune reconstitution on HIV-induced chronic systemic immune hyper-activation and its consequences
- clinical and lab assessment Imaging, EKG and Ultrasound IL-7 Pharmacokinetics and Immunogenicity IL-7 Pharmacodynamics/Immunology Bacterial Translocation and HLA typing [ Time Frame: every 3 months up to the end of study period 2years ] [ Designated as safety issue: Yes ]
Immune Monitoring will consist on T-cell subsets identification and quantification (such as RTE, naïve/effector and memory CD4 and CD8 T-cells, B cells, CD4 CD25 Fox P3 regulatory T-cells), quantification of the expression of CD127 and the evaluation of T-cell cycling and survival.
T-cell Repertoire Diversity:
Thymopoiesis Evaluation: Quantification of sjTRECs and βTRECs will be done by Real Time Quantitative PCR, and Ratio values will be analyzed.
GUT Biopsy - T-cell Homing :Essential receptors expression for intestinal homing, namely the integrin α4β7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 could be assessed as well as molecules for T-cell trafficking (CCR7, CXCR4, CXCL12...) in the gut biopsies.
Immunogenicity: antidrug antibody (ADA) and neutralizing ADA will be tested. In case of a positive sample, the test will be repeated every 3 months until negative.
|Study Start Date:||January 2010|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
|Experimental: CYT107 (r-hIL-7)||
20 µg/kg/week. 3 administrations, 1 per week (1 cycle) repeated cycles based on a CD4-guided response
Other Name: CYT107
This was a phase IIa study assessing weekly doses of CYT107 in addition to antiviral treatment (HAART) in adult patients with HIV.
CYT107 were administered at the dose of 20 µg/kg based on the patient's weight, in 3 weekly administrations. CYT107 Subcutaneous injection administered at the clinic or day hospital
Patients were followed every 3 months for primary and secondary biological activity criteria as well as safety up to 24 months long term follow-up with quarterly visits.
A cycle = 3 weekly administrations; D/d0; D/d7; D/d14 For all patients there will be a maximum of 3 cycles over 12 months and a maximum of 4 cycles over 21 months, for a total duration on study of 24 months.
All patients were receiving and continued to receive combination antiretroviral therapy while on-study.
Pre-medication was not be used systematically but might be administered if needed according to standard clinical practice.
During the study visits the following may be done:
- Medical history, physical examination, blood tests every visit.
- Electrocardiogram (EKG)
- Chest x-ray study
- Liver/spleen imaging
- Blood sample collections at frequent intervals for laboratory tests (Virology: HIV RNA &HIV DNA;Pharmacodynamics/Immunology;Bacterial translocation )
- Urine tests several times during the study.
PBMCs collections for immunological testing
An optional substudy on gut biopsy performed prior and at month 3 after the first CYT107 cycle to evaluate T cell homing
Please refer to this study by its ClinicalTrials.gov identifier: NCT01190111
|United States, Florida|
|University of Miami School of Medicine|
|Miami, Florida, United States, 33136|
|United States, Maryland|
|Bethesda, Maryland, United States, 20892|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|McGill University Health Center (MUHC)|
|Montreal, Quebec, Canada, H2X 2P4|
|Study Chair:||Michael M. Lederman,, Pr||Case Western Reserve University|