AIDS 347: IL-6 Blockade in Treated HIV Infection

Phase 1

Completed

Conditions: HIV Infections

Interventions: Drug: tocilizumab
Drug: Placebo

Registration Number: NCT02049437

Lead Sponsor: Case Western Reserve University

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)

Detailed Description: DESIGN 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)

DURATION 40 weeks during cross-over treatment periods total per subject.

SAMPLE SIZE 30 subjects with complete data up to week 30. Up to 36 subjects may be enrolled in order to achieve an estimated final sample size of 30 participants with complete data up to week 30.

POPULATION HIV-infected male and female subjects from 18 through 60 years of age receiving combination antiretroviral therapy (ART) without changes in the 24 weeks prior to enrollment (changes for reasons other than virologic failure allowed up to 8 weeks prior to enrollment), with a suppressed plasma HIV RNA (\<200 copies/mL, one blip up to \<1,000 copies/mL permitted) for at least 96 weeks and a CD4+ T-cell count ≥350 and ≤1,000 cells/mm3 at the time of study enrollment.

REGIMEN 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 24, followed by TCZ, 8 mg/Kg (not to exceed 800 mg) by IV infusion over 60 minutes at weeks 24 and 28.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm A: TCZ, then placebo	Placebo	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, then TCZ	Placebo	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.
Arm A: TCZ, then placebo	tocilizumab	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, then TCZ	tocilizumab	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.

Primary Outcome Measures

Name	Time	Method
Number of Grade 2 or Greater AEs	30 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Serum C-reactive Protein Change Between Beginning and End of Treatment Period	study entry - 10 weeks; 20 weeks - 30 weeks	The primary analysis of the two co-primary (CRP and T cell cycling) endpoints will specifically focus on the changes from study entry to week 10 and from week 20 to week 30.
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	The primary analysis of the two co-primary (CRP and T cell cycling) endpoints will specifically focus on the changes from study entry to week 10 and from week 20 to week 30.