HIV Reservoir Reduction With Interleukin-2

NCT03308786 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: AIDS 400: IL2
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot study is to examine the effects of eight 4-day cycles of subcutaneous recombinant interleukin-2 (rIL-2) given every 8 weeks on levels of replication-competent HIV in CD4 cells and on the size of HIV viral reservoir in up to 20 participants with chronically suppressed HIV infection (viral load \<50 copies/mL).

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (1)

• Latent HIV Reservoir Change by QVOA

  Change in the number of infectious units per million resting CD4+ T cells (IUPM) from baseline to the end of study treatment, as measured by the Quantitative Viral Outgrowth Assay (QVOA).

  15 months

Secondary Outcomes (7)

• Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by Intact Proviral DNA.

  15 months

• Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by the Tat-rev Inducible Limiting Dilution Assay (TILDA).

  15 months

• Correlation of Latent Reservoir Measure by QVOA to Latent Reservoir Measure by the Envelope Detection by Induced Transcription-based Sequencing (EDITS)

  15 months

• In Vivo Induction of HIV Expression in Vivo as Measured by the Envelope Detection by Induced Transcription-based Sequencing (EDITS)

  15 months

• Plasma HIV RNA During rIL2 Exposure

  baseline, day 7

Study Arms (1)

IL2 treatment

EXPERIMENTAL

Subcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles, in addition to combination antiretroviral therapy.

Drug: Recombinant Interleukin-2

Interventions

Recombinant Interleukin-2 DRUG

Subcutaneous recombinant interleukin-2 (rIL2), 5 MIU twice daily for four consecutive days(cycle) every 8 weeks for 8 cycles

Also known as: IL2, IL-2, rIL2, aldesleukin

IL2 treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed and dated by study participant.
• Male or female, at least 18 years of age and not older than 65 years of age.
• HIV-1 infection, documented by and FDA-approved ELISA, EIA, or rapid antibody detection method, and confirmed by a second approved antibody-based test or by a positive approved HIV RNA detection assay.
• CD4+ T cell count ≥ 350 cells/mm3;
• HIV-1 RNA \< 50 copies/mL obtained within 60 days prior to study entry performed with an FDA-approved HIV-1 RNA assay.
• Adequate venous access and no other contraindications for leukapheresis
• Absolute neutrophil count (ANC) \> 2000/mm3
• Hemoglobin level \>10 g/dL (males); \> 9.5 g/dL (females)
• Platelet count \>150,000/mm3
• Serum creatinine \<1.5 mg/dL
• AST and ALT \<2.5 times the upper limit of normal
• TSH, T3, and T4 levels within the normal range of the processing laboratory.
• Anti-thyrosine peroxidase (TPO) within the normal range of the processing laboratory.
• Willing to comply with study-mandated evaluations; including not changing antiretroviral regimen (unless medically indicated) during the study period.
• All participants must have received HAART, and had viral loads below the limit of quantification of the assay for at least 1 year. Participants who had intermittent isolated episodes of detectable low-level viremia \< 500 copies RNA/mL flanked by viral loads below the limit of quantification of the assay will remain eligible.

You may not qualify if:

• Childbearing potential for female participants. For the purposes of this study, a woman is considered to be of childbearing potential if she is postmenarche, has not had a documented surgical sterilization procedure, has an intact uterus and at least 1 ovary, and has had a spontaneous menstrual period in the last 2 years.
• Acute or chronic hepatitis C infection, defined as a positive plasma HCV RNA using any FDA-approved qualitative or quantitative test in a participant with a positive HCV antibody (HCV RNA testing is not required in participants with a negative HCV antibody). Participants who have completed a course of a direct-acting antiviral agent for hepatitis C and have a confirmed plasma HCV RNA level below the limit of detection of the assay 12 weeks or longer after completion of therapy will be eligible.
• Acute or chronic hepatitis B infection, defined as a positive HBV surface antigen or a positive HBV DNA.
• History of advanced chronic liver disease, including cirrhosis, advanced liver fibrosis, severe portal hypertension, or manifestations or hepatic failure.
• History of malignant disease that is not considered to be surgically or medically eradicated or that has required any form of therapy in the past 5 years.
• Current diagnosis of congestive heart failure of any severity, uncontrolled angina or uncontrolled arrhythmias.
• History of chronic lung disease that has required pharmacologic treatment, oxygen supplementation, medical monitoring, or hospitalization in the previous year, or that is expected to cause persistent or recurrent pulmonary symptoms or impairment. Examples of the latter include but are not limited to chronic bronchitis, emphysema, and pulmonary fibrosis.
• History or any features on physical examination indicative of a bleeding diathesis.
• History or current diagnosis of thromboembolic disease, including deep vein thrombosis and pulmonary embolism, or family history of the same.
• History of hypersensitivity to radiological contrast media or anticipated need for exposure to radiological contrast media during the study period.
• Use of chronic corticosteroids, hydroxyurea, or immune-modulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to enrollment.
• Breast-feeding.
• Use of aspirin, warfarin or any other antithrombotic or antiplatelet agent during the 2-week period prior to leukapheresis.
• History of autoimmune disorders, including but not limited to Crohn's disease, scleroderma, thyroiditis, inflammatory arthritis, myasthenia gravis, glomerulonephritis, systemic lupus erythematous, and vasculitis.
• Type 1 diabetes mellitus.

Sponsors & Collaborators

• Case Western Reserve University: lead

Study Sites (1)

AIDS Clinical Trials Unit

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Limitations and Caveats

On the basis of recommendation of the SMC, the study was terminated. Because of this, the primary objective could not be achieved and most of the secondary objectives could not be achieved.

Results Point of Contact

• Title: Michael M. Lederman MD
• Organization: Case Western Reserve University

MXL6@CASE.EDU

2168448786

Study Officials

• Benigno Rodriguez, MD

  Case Western Reserve University

  STUDY CHAIR

• Michael Lederman, MD

  Case Western Reserve University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 13, 2017
• Study Start: April 1, 2019
• Primary Completion: August 20, 2020
• Study Completion: August 20, 2020
• Last Updated: September 28, 2022
• Results First Posted: September 28, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)