Trial Outcomes & Findings for AIDS 347: IL-6 Blockade in Treated HIV Infection (NCT NCT02049437)
NCT ID: NCT02049437
Last Updated: 2024-08-06
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
34 participants
Primary outcome timeframe
30 weeks
Results posted on
2024-08-06
Participant Flow
Participant milestones
| Measure |
Arm A: TCZ, Then 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
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 min once at week 20, followed by TCZ, 8 mg/Kg (not to exceed 800 mg) by IV infusion over 60 min at weeks 24 and 28.
|
|---|---|---|
|
Period 1
STARTED
|
17
|
17
|
|
Period 1
COMPLETED
|
15
|
16
|
|
Period 1
NOT COMPLETED
|
2
|
1
|
|
Washout 1
STARTED
|
15
|
16
|
|
Washout 1
COMPLETED
|
15
|
16
|
|
Washout 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
15
|
16
|
|
Period 2
COMPLETED
|
15
|
16
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
|
Washout 2
STARTED
|
15
|
16
|
|
Washout 2
COMPLETED
|
15
|
16
|
|
Washout 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Arm A: TCZ, Then 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
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 min once at week 20, followed by TCZ, 8 mg/Kg (not to exceed 800 mg) by IV infusion over 60 min at weeks 24 and 28.
|
|---|---|---|
|
Period 1
Adverse Event
|
1
|
0
|
Baseline Characteristics
AIDS 347: IL-6 Blockade in Treated HIV Infection
Baseline characteristics by cohort
| Measure |
Arm A: TCZ, Then Placebo
n=17 Participants
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
n=17 Participants
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.
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47 years
n=5 Participants
|
49 years
n=7 Participants
|
48 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
17 participants
n=7 Participants
|
34 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 30 weeksThe 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).
Outcome measures
| Measure |
Tocilizumab
n=31 Participants
Patients from Arm A that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) once at study entry, followed by TCZ, 8 mg/kg by IV infusion over 60 min (not to exceed 800 mg) at weeks 4, and 8.
Patients from Arm B that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) 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 after the first (placebo) interventional period and washout period
|
Placebo
n=31 Participants
Patients from Arm A that, after washout period 1, obtained placebo by IV infusion at weeks 20, 24 and 28.
Patients from Arm B that obtained placebo by IV infusion at study entry followed by placebo by IV infusion at weeks 4 and 8.
|
|---|---|---|
|
Number of Grade 2 or Greater AEs
|
10 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: study entry - 10 weeks; 20 weeks - 30 weeksThe 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.
Outcome measures
| Measure |
Tocilizumab
n=31 Participants
Patients from Arm A that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) once at study entry, followed by TCZ, 8 mg/kg by IV infusion over 60 min (not to exceed 800 mg) at weeks 4, and 8.
Patients from Arm B that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) 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 after the first (placebo) interventional period and washout period
|
Placebo
n=31 Participants
Patients from Arm A that, after washout period 1, obtained placebo by IV infusion at weeks 20, 24 and 28.
Patients from Arm B that obtained placebo by IV infusion at study entry followed by placebo by IV infusion at weeks 4 and 8.
|
|---|---|---|
|
Serum C-reactive Protein Change Between Beginning and End of Treatment Period
Serum C-reactive protein at either study entry or week 20
|
4316 ng/mL
Standard Deviation 6907
|
3320 ng/mL
Standard Deviation 4149
|
|
Serum C-reactive Protein Change Between Beginning and End of Treatment Period
Serum C-reactive protein at either 10 weeks or 30 weeks
|
157 ng/mL
Standard Deviation 183
|
2256 ng/mL
Standard Deviation 1928
|
SECONDARY outcome
Timeframe: study entry - 10 weeks; 20 weeks - 30 weeksThe 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.
Outcome measures
| Measure |
Tocilizumab
n=31 Participants
Patients from Arm A that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) once at study entry, followed by TCZ, 8 mg/kg by IV infusion over 60 min (not to exceed 800 mg) at weeks 4, and 8.
Patients from Arm B that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) 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 after the first (placebo) interventional period and washout period
|
Placebo
n=31 Participants
Patients from Arm A that, after washout period 1, obtained placebo by IV infusion at weeks 20, 24 and 28.
Patients from Arm B that obtained placebo by IV infusion at study entry followed by placebo by IV infusion at weeks 4 and 8.
|
|---|---|---|
|
Change in Proportion of Central Memory T Cells Expressing Ki67 Between Beginning and End of Treatment Period
proportion of central memory T cells expressing Ki67 at either study entry or 20 weeks
|
0.0689 proportion of central memory T cells
Standard Deviation 0.0222
|
0.0721 proportion of central memory T cells
Standard Deviation 0.0293
|
|
Change in Proportion of Central Memory T Cells Expressing Ki67 Between Beginning and End of Treatment Period
proportion of central memory T cells expressing Ki67 at either 10 weeks or 30 weeks
|
0.0685 proportion of central memory T cells
Standard Deviation 0.0192
|
0.0708 proportion of central memory T cells
Standard Deviation 0.0222
|
Adverse Events
Tocilizumab
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Tocilizumab
n=33 participants at risk
Patients from Arm A that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) once at study entry, followed by TCZ, 8 mg/kg by IV infusion over 60 min (not to exceed 800 mg) at weeks 4, and 8.
Patients from Arm B that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) 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 after the first (placebo) interventional period and washout period
|
Placebo
n=32 participants at risk
Patients from Arm A that, after washout period 1, obtained placebo by IV infusion at weeks 20, 24 and 28.
Patients from Arm B that obtained placebo by IV infusion at study entry followed by placebo by IV infusion at weeks 4 and 8.
|
|---|---|---|
|
Blood and lymphatic system disorders
Severe neutropenia
|
3.0%
1/33 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
0.00%
0/32 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
Other adverse events
| Measure |
Tocilizumab
n=33 participants at risk
Patients from Arm A that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) once at study entry, followed by TCZ, 8 mg/kg by IV infusion over 60 min (not to exceed 800 mg) at weeks 4, and 8.
Patients from Arm B that obtained TCZ, 4 mg/kg by IV infusion over 60 min (not to exceed 400 mg) 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 after the first (placebo) interventional period and washout period
|
Placebo
n=32 participants at risk
Patients from Arm A that, after washout period 1, obtained placebo by IV infusion at weeks 20, 24 and 28.
Patients from Arm B that obtained placebo by IV infusion at study entry followed by placebo by IV infusion at weeks 4 and 8.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Sinus Infection
|
3.0%
1/33 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
0.00%
0/32 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Injury, poisoning and procedural complications
radius fracture
|
3.0%
1/33 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
0.00%
0/32 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Metabolism and nutrition disorders
Weight loss
|
3.0%
1/33 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
0.00%
0/32 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Skin and subcutaneous tissue disorders
Hidradentitis Suppurativa
|
3.0%
1/33 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
0.00%
0/32 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Renal and urinary disorders
Urinary tract infection
|
0.00%
0/33 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
3.1%
1/32 • Number of events 2 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract infection
|
0.00%
0/33 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
3.1%
1/32 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/33 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
3.1%
1/32 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Musculoskeletal and connective tissue disorders
Acute gout flare
|
0.00%
0/33 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
3.1%
1/32 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Gastrointestinal disorders
Viral gastroenteritis
|
0.00%
0/33 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
3.1%
1/32 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
Skin and subcutaneous tissue disorders
Cellulitis
|
0.00%
0/33 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
3.1%
1/32 • Number of events 1 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
|
General disorders
Abnormal blood test
|
63.6%
21/33 • Number of events 45 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
46.9%
15/32 • Number of events 29 • Adverse event data were collected over the total length of the trial, 40 weeks.
33 patients were at risk for adverse events during the Toculizumab treatment: 17 patients in arm A that started Toculizumab in period 1 + 16 patients in arm B that started Toculizumab in period 2 32 patients were at risk for adverse events during the placebo treatment: 17 patients in arm B that started placebo in period 1 + 15 patients in arm A that started placebo treatment in period 2
|
Additional Information
Marijke Frederix, PhD
University Hospitals Cleveland Medical Center
Phone: (216) 844-0383
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place