Study on Interleukin-7 (CYT107) in HIV Patients

HIV Clinical Trial

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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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01190111
• Other study ID #: CLI-107-13
• Status: Terminated
• Phase: Phase 2
• First received: August 23, 2010
• Last updated: July 31, 2013
• Start date: January 2010
• Est. completion date: June 2013

Study information

• Verified date: July 2013
• Source: Cytheris SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western Blot at any time prior to study entry.

• Age =18.

• On HAART for at least 12 months, on stable regimen for at least 3 months prior to enrollment. HAART is defined as a combination of 2 classes dose regimen of approved ARV.

• CD4 cell counts = 101 and < 400 cells/mm3 on two (2) consecutive measurements (including the screening value) within the previous 12 months prior to enrollment.

• Plasma HIV RNA < 50 copies/mL on at least two consecutive measurements (including the screening value) within the previous 6 months prior to enrollment. Note: Patients with single blip of detectable viremia during this period (6 months prior screening) will be allowed to participate if the prior and subsequent plasma HIV RNA levels are below the limits of detection.

• No AIDS-defining illness (category C) diagnosed within the last 6 months prior to enrollment.

Exclusion Criteria:

• Use of any other investigational antiretroviral agents.

• Any planned or probable modification of the anti-retroviral treatment during the first 3 month study period.

• Current or recent history (<30 days prior to screening) of a viral, bacterial, parasitic or fungal infection requiring systemic treatment and/or hospitalization.

• Positive PPD unless there is documentation of completion of INH therapy for latent tuberculosis.

• Any serious illness requiring systemic treatment and/or hospitalization until the patient either completes therapy or is clinically stable on therapy, in the opinion of the principal investigator, for at least 28 days prior to study .

• Any history of malignancy (except basal carcinoma of the skin) including any hematologic malignancy or AIDS defining malignancy, such as lymphoproliferative disorder or Kaposi's sarcoma. (Patients with Kaposi's sarcoma limited to the skin that disappeared while on HAART therapy, and without requiring any other systemic therapy, 1 year prior to study entry will be eligible to participate).

• Any history of HIV related encephalopathy.

• Hepatitis B or C (positive HBs Ag or positive anti HBc antibodies with a detectable HBV DNA viral load or positive anti HCV antibodies with a detectable HCV RNA viral load). Patients who became negative to HBV DNA or HCV RNA following an antiviral treatment should not be enrolled.

• HIV-2, HTLV-1 or HTLV-2 seropositivity.

• Pregnant or lactating women. Women of childbearing potential must have a negative serum or urine pregnancy test within 1 week prior to study entry.

• Refusal or inability to practice contraception regardless of the gender of the patient.

• Hypertension with a resting systolic blood pressure > 140 or a resting diastolic blood pressure > 90 mm despite adequate antihypertensive treatment.

• Use of tipranavir/ritonavir (TPV/r) and Enfuvirtide (T-20).

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV

Intervention

Biological:
• Interleukin-7
20 µg/kg/week. 3 administrations, 1 per week (1 cycle) repeated cycles based on a CD4-guided response

Locations

Country	Name	City	State
Canada	McGill University Health Center (MUHC)	Montreal	Quebec
United States	Niaid/Nih	Bethesda	Maryland
United States	Case Western Reserve University	Cleveland	Ohio
United States	University of Miami School of Medicine	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Cytheris SA

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	clinical and lab assessment Imaging, EKG and Ultrasound IL-7 Pharmacokinetics and Immunogenicity IL-7 Pharmacodynamics/Immunology Bacterial Translocation and HLA typing	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 ßTRECs 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 a4ß7 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.	every 3 months up to the end of study period 2years	Yes
Primary	• 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.		2 years (24 months)	Yes
Secondary	• 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. • • •	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	2 years	Yes