AIDS 347: IL-6 Blockade in Treated HIV Infection

NCT02049437 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: AIDS 347IL-6
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a phase I/II, double-blind, placebo-controlled, randomized cross-over clinical trial of tocilizumab (TCZ) or placebo in HIV-infected subjects receiving antiretroviral therapy with suppressed viral replication and CD4+ T cell count ≥350 and ≤1,000 cells/mm3)

Conditions

HIV Infections

Keywords

HIV; Immune failure; Tocilizumab; ACTEMRA; Antiretroviral therapy; HAART

Outcome Measures

Primary Outcomes (1)

• Number of Grade 2 or Greater AEs

  The number and percentage of participants experiencing at least one grade ≥2 clinical or laboratory adverse event related to study treatment during each period (0 to 10 weeks for Period 1 or 20 to 30 weeks for Period 2).

  30 weeks

Secondary Outcomes (2)

• Serum C-reactive Protein Change Between Beginning and End of Treatment Period

  study entry - 10 weeks; 20 weeks - 30 weeks

• Change in Proportion of Central Memory T Cells Expressing Ki67 Between Beginning and End of Treatment Period

  study entry - 10 weeks; 20 weeks - 30 weeks

Study Arms (2)

Arm A: TCZ, then placebo

ACTIVE COMPARATOR

ARM A: TCZ, 4 mg/Kg by IV infusion over 60 minutes (not to exceed 400 mg) once at study entry, followed by TCZ, 8 mg/Kg by IV infusion over 60 minutes (not to exceed 800 mg) at weeks 4 and 8, and THEN placebo by IV infusion at weeks 20, 24, and 28.

Drug: tocilizumab; Drug: Placebo

Arm B: Placebo, then TCZ

PLACEBO COMPARATOR

ARM B: Placebo by IV infusion at study entry followed by placebo by IV infusion at weeks 4 and 8, and THEN TCZ, 4 mg/Kg (not to exceed 400 mg) by IV infusion over 60 minutes once at week 20, followed by TCZ, 8 mg/Kg (not to exceed 800 mg) by IV infusion over 60 minutes at weeks 24 and 28.

Drug: tocilizumab; Drug: Placebo

Interventions

tocilizumab DRUG

Subjects will be randomized 1:1 to one of the following arms: ARM A: TCZ, 4 mg/Kg by IV infusion over 60 minutes (not to exceed 400 mg) once at study entry, followed by TCZ, 8 mg/Kg by IV infusion over 60 minutes (not to exceed 800 mg) at weeks 4 and 8, and THEN placebo by IV infusion at weeks 20, 24, and 28. ARM B: Placebo by IV infusion at study entry followed by placebo by IV infusion at weeks 4 and 8, and THEN TCZ, 4 mg/Kg (not to exceed 400 mg) by IV infusion over 60 minutes once at week 20, followed by TCZ, 8 mg/Kg (not to exceed 800 mg) by IV infusion over 60 minutes at weeks 24 and 28.

Also known as: TCZ

Arm A: TCZ, then placebo; Arm B: Placebo, then TCZ

Placebo DRUG

Subjects will be randomized 1:1 to one of the following arms: ARM A: TCZ, 4 mg/Kg by IV infusion over 60 minutes (not to exceed 400 mg) once at study entry, followed by TCZ, 8 mg/Kg by IV infusion over 60 minutes (not to exceed 800 mg) at weeks 4 aned 8, and THEN placebo by IV infusion at weeks 20, 24, and 28. ARM B: Placebo by IV infusion at study entry followed by placebo by IV infusion at weeks 4 and 8, and THEN TCZ, 4 mg/Kg (not to exceed 400 mg) by IV infusion over 60 minutes once at week 20, followed by TCZ, 8 mg/Kg (not to exceed 800 mg) by IV infusion over 60 minutes at weeks 24 and 28.

Also known as: Normal saline for infusion

Arm A: TCZ, then placebo; Arm B: Placebo, then TCZ

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women age 18-60 years.
• Ability and willingness to communicate in English or Spanish
• Ability and willingness of subject to provide informed consent.
• Ability and willingness to provide adequate locator information.
• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test at any time before study entry and confirmed by a licensed Western blot, a second antibody test by a method other than rapid HIV or E/CIA; HIV-1 antigen; or plasma HIV-1 RNA viral load.
• Receiving a stable antiretroviral regimen consisting of 3 or more drugs belonging to two or more classes, one of which must be a protease inhibitor, an integrase inhibitor, or a non-nucleoside reverse transcriptase inhibitor, without any changes due to virologic failure in the past 24 weeks, and with no plans to change antiretroviral regimen in the 40 weeks following enrollment. If the regimen includes a protease inhibitor, ritonavir or an approved boosting agent known to increase trough levels of the protease inhibitor by at least 50% must also be a part of the regimen.
• NOTE A: Changes to the antiretroviral regimen 8 weeks or more prior to enrollment are allowed if the plasma HIV RNA was \<50 copies/mL at the time of the change, the reason for the change was not suspicion or documentation of virologic failure, and all other criteria for virologic control, as outlined in criterion 4.1.9 below, are met.
• NOTE B: For the purposes of this protocol, "a change due to virologic failure" is defined as any of the following events or combinations thereof happening in a patient who is receiving uninterrupted combination antiretroviral therapy including at least three agents belonging to at least two classes: a) plasma HIV RNA is \>200 copies/mL on two or more consecutive occasions; b) the treating physician determines that any given plasma HIV RNA value is indicative or suggestive of virologic failure, and recommends that the patient's regimen be modified as a result; c) a genotypic or phenotypic antiretroviral resistance test identifies the presence of resistance to any component of a patient's regimen that was not present before, and a physician recommends that the patient's regimen be modified as a result.
• For subjects who have a positive HBcAb only:
• An antiretroviral regimen containing one or more of the following medications: lamivudine, emtricitabine, or tenofovir.
• Screening CD4+ T-cell count ≥350 cells/mm3 but ≤1,000 cells/mm3 performed in a laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
• HIV-1 RNA \<200 copies/mL at every time a plasma HIV RNA has been obtained, but no fewer than twice, in the 96 weeks prior to enrollment.
• NOTE: One plasma HIV RNA above 200 copies/mL but lower than 1,000 copies in the 96 weeks prior to enrollment is permissible if flanked by two measurements that are both below 200 copies. The HIV-1 RNA at screening must be \<50 copies/mL.
• The following laboratory values obtained within 60 days prior to entry:
• Hgb ≥10 g/dL

You may not qualify if:

• History of one of the following opportunistic infections at any time in the past, as demonstrated by either a patient-reported or physician-documented diagnosis AND the initiation of specific treatment if applicable:
• Tuberculosis, pulmonary or extrapulmonary
• Non-tuberculous mycobacterial infection, disseminated or extrapulmonary
• Pneumocystis jirovecii pneumonia
• Coccidioidomycosis, disseminated or extrapulmonary
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis or isosporiasis, chronic intestinal (greater than 1 month's duration)
• Cytomegalovirus disease (other than liver, spleen, or lymph nodes) and including retinitis with loss of vision
• Histoplasmosis, disseminated or extrapulmonary
• Kaposi's sarcoma
• Lymphoma, Burkitt's or immunoblastic, regardless of anatomical location
• Lymphoma, primary of brain
• Progressive multifocal leukoencephalopathy
• Toxoplasmosis of brain
• Latent tuberculosis infection, defined as a positive or borderline FDA-approved interferon-gamma release assay (IGRA).

Sponsors & Collaborators

• Case Western Reserve University: lead

Study Sites (1)

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Related Publications (1)

• Funderburg NT, Shive CL, Chen Z, Tatsuoka C, Bowman ER, Longenecker CT, McComsey GA, Clagett BM, Dorazio D, Freeman ML, Sieg SF, Moisi D, Anthony DD, Jacobson JM, Stein SL, Calabrese LH, Landay A, Flexner C, Crawford KW, Capparelli EV, Rodriguez B, Lederman MM. Interleukin 6 Blockade With Tocilizumab Diminishes Indices of Inflammation That Are Linked to Mortality in Treated Human Immunodeficiency Virus Infection. Clin Infect Dis. 2023 Jul 26;77(2):272-279. doi: 10.1093/cid/ciad199.

  PMID: 37011013 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

tocilizumab; Saline Solution

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)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Marijke Frederix, PhD
• Organization: University Hospitals Cleveland Medical Center

marijke.frederix@UHhospitals.org

(216) 844-0383

Study Officials

• Benigno Rodriguez, MD

  Case Western Reserve University

  STUDY CHAIR

• Michael Lederman, MD

  Case Western Reserve University

  STUDY CHAIR

• George Yendewa, MD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2014
• First Posted: January 30, 2014
• Study Start: August 1, 2014
• Primary Completion: September 11, 2017
• Study Completion: September 11, 2017
• Last Updated: August 6, 2024
• Results First Posted: December 17, 2020

Record last verified: 2024-08

Locations

US (1)