Ibalizumab Plus Optimized Background Regimen in Patient With Multi-Drug Resistant HIV

A Phase 3, Single Arm, 24-Week, Multicenter Study of Ibalizumab Plus an Optimized Background Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug Resistant HIV-1

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02475629

Enrollment

Registered

2015-06-19

Start date

2015-08-31

Completion date

2016-12-31

Last updated

2020-03-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV

Brief summary

This Phase 3, single arm, multicenter study will evaluate the safety and effectiveness of ibalizumab in treatment-experienced patients infected with multi-drug resistant HIV-1.

Detailed description

This Phase 3, single arm, multicenter study will evaluate the safety and effectiveness of ibalizumab in treatment-experienced patients infected with multi-drug resistant HIV-1. Patients must have been treated with HAART for at least 6 months and be failing or have recently failed (i.e., in the last 8 weeks) therapy to determine baseline viral load. Days 0-6 of the study will be a control period. During Days 0 through 6 patients will be monitored on current failing therapy (or no therapy, if the patient has failed and discontinued treatment within the 8 weeks preceding Screening). Days 7-13 of the study will be an essential monotherapy period. During Days 7 through 13 patients will continue on current failing therapy and receive one 2000 mg dose (loading dose) of ibalizumab on Day 7. Day 7 is Baseline for the treatment period (Day 7-Week 25). Day 14-Week 25 of the study will be the maintenance period. On Day 14 (primary endpoint), the OBR will be initiated and must include at least one agent to which the patient's virus is susceptible. Beginning at Day 21, 800 mg of ibalizumab will be administered every 2 weeks through Week 23. End of Study evaluations will be performed at Week 25, and a follow-up visit will be conducted at Week 29.

Interventions

BIOLOGICALibalizumab

2000mg intravenous ibalizumab (loading dose), followed 14 days later by 800mg intravenous ibalizumab every 2 weeks

DRUGOptimized Background Regimen (OBR)

All participants will be prescribed an Optimized Background Regimen of antiretroviral medications selected on the basis of treatment history and the results of Screening viral resistance and tropism testing. The prescribed regimen must contain at least one agent to which the participant's virus is known to be sensitive.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Are capable of understanding and have voluntarily signed the informed consent document * Have documented HIV-1 infection by official, signed, written history (e.g., laboratory report), otherwise an HIV-antibody test will be performed * Have no acquired immunodeficiency syndrome (AIDS)-defining events in the 3 months before Screening, other than cutaneous Kaposi's sarcoma or wasting syndrome due to HIV * Are able and willing to comply with all protocol requirements and procedures * Have a life expectancy that is \>6 months. * Have a viral load \>1,000 copies/mL and documented resistance to at least one antiretroviral medication from each of three classes of antiretroviral medications as measured by resistance testing * Have a history of at least 6 months on antiretroviral treatment * Are receiving a stable highly active antiretroviral regimen for at least 8 weeks before Screening and are willing to continue that regimen until Day 14, OR (in the past 8 weeks) have failed and are off therapy and are willing to stay off therapy until Day 14 * Have full viral sensitivity/susceptibility to at least one antiretroviral agent, other than ibalizumab, as determined by the screening resistance tests and be willing and able to be treated with at least one agent to which the patient's viral isolate is fully sensitive/susceptible according to the screening resistance tests as a component of OBR * If sexually active, are willing to use an effective method of contraception during the study and for 30 days after the last administration of the study drug

Exclusion criteria

* Any active AIDS-defining illness per Category C conditions according to the Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection, with the following exceptions: cutaneous Kaposi's sarcoma and wasting syndrome due to HIV * Any significant diseases (other than HIV-1 infection) or clinically significant findings, including psychiatric and behavioral problems, determined from screening, medical history and/or physical examination that, in the investigator's opinion, would preclude the patient from participating in this study * Any significant acute illness within 1 week before the initial administration of study drug * Any active infection secondary to HIV requiring acute therapy; however, patients that require maintenance therapy (i.e., secondary prophylaxis for opportunistic infections) will be eligible for the study. * Any immunomodulating therapy (including interferon), systemic steroids, or systemic chemotherapy within 12 weeks before Enrollment * Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8) * Any vaccination within 7 days before Enrollment * Any female patient who either is pregnant, intends to become pregnant, or is currently breastfeeding * Any current alcohol or illicit drug use that, in the investigator's opinion, will interfere with the patient's ability to comply with the study schedule and protocol evaluations * Any previous clinically significant allergy or hypersensitivity to any excipient in the ibalizumab formulation * Any radiation therapy during the 28 days before first administration of investigational medication * Any Grade 3 or 4 laboratory abnormality according to the Division of AIDS grading scale, except for the following asymptomatic Grade 3 events triglyceride elevation total cholesterol elevation

Design outcomes

Primary

Measure	Time frame	Description
Efficacy: Proportion of Subjects With a Viral Load Decrease of at Least 0.5 Log 10 - Protocol Correct	Day 14	Proportion of patients (%) with a viral load decrease of at least 0.5 log 10 from baseline (day 7)
Efficacy: Proportion of Participants Achieving a Viral Load Reduction of at Least 0.5 Log 10: ITT-MEF	Day 14	Proportion of participants (%) achieving a viral load reduction of at least 0.5 log from baseline (Day 7)

Secondary

Measure	Time frame	Description
Efficacy: Proportion of Patients With Undetectable HIV-RNA Levels: Protocol Correct	Week 25/End of Study	Proportion of patients (%) with HIV-RNA levels \< 50 copies/mL and \< 400 copies/mL at Week 25/End of Study
Mean Change in Viral Load as a Measure of Efficacy - ITT-MEF	Day 7 and Day 14	Mean change from Day 7/Baseline in log 10 vial load measured at Day 14
Mean Change in Viral Load as a Measure of Efficacy - Protocol Correct	Day 7 and Day 14	Mean change from Day 7/Baseline in Log 10 viral load measured at Day 14
End of Study Viral Load Reductions as a Measure of Efficacy - Intent to Treat Analysis	at Week 25/End of Study	Proportion of patients achieving a \>/= 0.5 log10 and \>/= 1.0 log10 decrease from Day 7/Baseline in viral load at Week 25/End of Study
End of Study Viral Load Reductions as a Measure of Efficacy - Protocol Correct Analysis	at Week 25/End of Study	Proportion of patients achieving a \>/= 0.5 log10 and \>/= 1.0 log10 decrease from Day 7/Baseline in viral load at Week 25/End of Study
Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - ITT	Day 7 and Week 25/End of Study	Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study
Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - Protocol Correct	Day 7 and Week 25/End of Study	Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study
Proportion of Participants Experiencing Adverse Event Related to Study Drug as a Measure of Safety and Tolerability	Through Week 25/End of Study	Proportion of participants experiencing a treatment emergent adverse event determined by the investigator to be related to study drug
Proportion of Participants Experiencing Serious Adverse Event as a Measure of Safety and Tolerability	Through Week 25/End of Study	Proportion of participants experiencing at least one serious treatment emergent adverse event, excluding death
Proportion of Participants Discontinuing Study Drug Due to Adverse Event	Through Week 25/End of Study	Proportion of participants discontinuing study drug due to occurrence of treatment emergent adverse event
Proportion of Participants Experiencing Adverse Event Grade 3 and Higher as a Measure of Safety and Tolerability	Through Week 25/End of Study	Proportion of participants experiencing treatment emergent adverse event Grade 3 and higher
Proportion of Participants Experiencing Adverse Event With Death as Outcome as a Measure of Safety and Tolerability	Through Week 25/End of Study	Proportion of participants experiencing treatment emergent adverse event with death as the outcome, regardless of relationship to study drug
Proportion of Participants Experiencing New AIDS-defining Adverse Event According to CDC Criteria as a Measure of Safety and Tolerability	Through Week 25/End of Study	Proportion of participants experiencing treatment emergent adverse event that is AIDS-defining by the CDC adverse event classification criteria for HIV infection
Safety: Proportion of Participants Experiencing Adverse Events	Through Week 25/End of Study	Proportion of participants experiencing at least one treatment emergent adverse event to week 25/End of Study
Efficacy: Proportion of Patients With Undetectable Viral Load: ITT-MEF	Week 25 /end of study	Proportion of patients with undetectable Viral Load (\<50 copies/mL, and \<400 copies/mL)

Other

Measure	Time frame	Description
Pharmacodynamics: CD4 Receptor Occupancy	At Week 25/End of Study	% of CD receptors occupied by ibalizumab on CD4+ T-cells

Countries

Puerto Rico, Taiwan, United States

Participant flow

Participants by arm

Arm	Count
Open-Label Ibalizumab Plus OBR 2000 mg intravenous ibalizumab (loading dose) on Day 7 followed in 14 days (on Day 21) by 800 mg intravenous ibalizumab administered once every two weeks, plus an Optimized Background Regimen (OBR) beginning on Day 14. ibalizumab: 2000mg intravenous ibalizumab (loading dose), followed 14 days later by 800mg intravenous ibalizumab every 2 weeks Optimized Background Regimen (OBR): All participants will be prescribed an Optimized Background Regimen of antiretroviral medications selected on the basis of treatment history and the results of Screening viral resistance and tropism testing. The prescribed regimen must contain at least one agent to which the participant's virus is known to be sensitive.	40
Total	40

Arm

Count

Open-Label Ibalizumab Plus OBR

2000 mg intravenous ibalizumab (loading dose) on Day 7 followed in 14 days (on Day 21) by 800 mg intravenous ibalizumab administered once every two weeks, plus an Optimized Background Regimen (OBR) beginning on Day 14. ibalizumab: 2000mg intravenous ibalizumab (loading dose), followed 14 days later by 800mg intravenous ibalizumab every 2 weeks Optimized Background Regimen (OBR): All participants will be prescribed an Optimized Background Regimen of antiretroviral medications selected on the basis of treatment history and the results of Screening viral resistance and tropism testing. The prescribed regimen must contain at least one agent to which the participant's virus is known to be sensitive.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	1
Overall Study	Death	4
Overall Study	Lost to Follow-up	1
Overall Study	Physician Decision	1
Overall Study	Subject non-compliance	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Open-Label Ibalizumab Plus OBR
Age, Continuous	50.5 years STANDARD_DEVIATION 10.99
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	4 Participants
Race (NIH/OMB) Black or African American	13 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	22 Participants
Region of Enrollment Puerto Rico	2 participants
Region of Enrollment Taiwan	4 participants
Region of Enrollment United States	34 participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	34 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	4 / 40
other Total, other adverse events	32 / 40
serious Total, serious adverse events	9 / 40

Outcome results

Primary

Efficacy: Proportion of Participants Achieving a Viral Load Reduction of at Least 0.5 Log 10: ITT-MEF

Proportion of participants (%) achieving a viral load reduction of at least 0.5 log from baseline (Day 7)

Time frame: Day 14

Population: Intent to Treat (ITT) Population (all participants enrolled) with missing values set to zero change

Arm	Measure	Value (NUMBER)
Open-Label Ibalizumab Plus OBR	Efficacy: Proportion of Participants Achieving a Viral Load Reduction of at Least 0.5 Log 10: ITT-MEF	0.825 proportion of participants

Primary

Efficacy: Proportion of Subjects With a Viral Load Decrease of at Least 0.5 Log 10 - Protocol Correct

Proportion of patients (%) with a viral load decrease of at least 0.5 log 10 from baseline (day 7)

Time frame: Day 14

Population: Protocol Correct (PC) Population (all participants with non-missing viral load assessments at Day 7, Day 14 and Week 25/End of Study)

Arm	Measure	Value (NUMBER)
Open-Label Ibalizumab Plus OBR	Efficacy: Proportion of Subjects With a Viral Load Decrease of at Least 0.5 Log 10 - Protocol Correct	0.846 proportion of participants

Secondary

Efficacy: Proportion of Patients With Undetectable HIV-RNA Levels: Protocol Correct

Proportion of patients (%) with HIV-RNA levels \< 50 copies/mL and \< 400 copies/mL at Week 25/End of Study

Time frame: Week 25/End of Study

Population: Protocol Correct (PC) Population (all participants with non-missing viral load assessments at Day 7, Day 14 and Week 25/End of Study)

Arm	Measure	Group	Value (NUMBER)
Open-Label Ibalizumab Plus OBR	Efficacy: Proportion of Patients With Undetectable HIV-RNA Levels: Protocol Correct	<50 copies/mL	.654 proportion of participants
Open-Label Ibalizumab Plus OBR	Efficacy: Proportion of Patients With Undetectable HIV-RNA Levels: Protocol Correct	<400 copies/mL	.808 proportion of participants

Secondary

Efficacy: Proportion of Patients With Undetectable Viral Load: ITT-MEF

Proportion of patients with undetectable Viral Load (\<50 copies/mL, and \<400 copies/mL)

Time frame: Week 25 /end of study

Population: Intent to Treat (ITT) Population (all participants enrolled) with missing values set to failure

Arm	Measure	Group	Value (NUMBER)
Open-Label Ibalizumab Plus OBR	Efficacy: Proportion of Patients With Undetectable Viral Load: ITT-MEF	<50 copies/mL	.425 proportion of participants
Open-Label Ibalizumab Plus OBR	Efficacy: Proportion of Patients With Undetectable Viral Load: ITT-MEF	<400 copies/mL	.525 proportion of participants

Secondary

End of Study Viral Load Reductions as a Measure of Efficacy - Intent to Treat Analysis

Proportion of patients achieving a \>/= 0.5 log10 and \>/= 1.0 log10 decrease from Day 7/Baseline in viral load at Week 25/End of Study

Time frame: at Week 25/End of Study

Population: Intent to Treat (ITT) Population (all participants enrolled) with missing values set to zero change

Arm	Measure	Group	Value (NUMBER)
Open-Label Ibalizumab Plus OBR	End of Study Viral Load Reductions as a Measure of Efficacy - Intent to Treat Analysis	>/= 0.5 log10 reduction	.625 proportion of participants
Open-Label Ibalizumab Plus OBR	End of Study Viral Load Reductions as a Measure of Efficacy - Intent to Treat Analysis	>/= 1.0 log10 reduction	.550 proportion of participants

Secondary

End of Study Viral Load Reductions as a Measure of Efficacy - Protocol Correct Analysis

Proportion of patients achieving a \>/= 0.5 log10 and \>/= 1.0 log10 decrease from Day 7/Baseline in viral load at Week 25/End of Study

Time frame: at Week 25/End of Study

Population: Protocol Correct (PC) Population (all participants with non-missing viral load assessments at Day 7, Day 14 and Week 25/End of Study)

Arm	Measure	Group	Value (NUMBER)
Open-Label Ibalizumab Plus OBR	End of Study Viral Load Reductions as a Measure of Efficacy - Protocol Correct Analysis	>/= 0.5 log10 reduction	.962 proportion of participants
Open-Label Ibalizumab Plus OBR	End of Study Viral Load Reductions as a Measure of Efficacy - Protocol Correct Analysis	>/= 1.0 log10 reduction	.846 proportion of participants

Secondary

Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - ITT

Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study

Time frame: Day 7 and Week 25/End of Study

Population: Intent to Treat (ITT) Population (all participants enrolled). Only obtained values were included in analysis - missing values were not imputed.

Arm	Measure	Value (MEAN)	Dispersion
Open-Label Ibalizumab Plus OBR	Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - ITT	62.4 cells/mm^3	Standard Deviation 105.75

Secondary

Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - Protocol Correct

Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study

Time frame: Day 7 and Week 25/End of Study

Population: Protocol Correct (PC) Population (all participants with non-missing viral load assessments at Day 7, Day 14 and Week 25/End of Study) with non-missing CD4+ cell count measurements

Arm	Measure	Value (MEAN)	Dispersion
Open-Label Ibalizumab Plus OBR	Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - Protocol Correct	67.0 cells/mm^3	Standard Deviation 114.35

Secondary

Mean Change in Viral Load as a Measure of Efficacy - ITT-MEF

Mean change from Day 7/Baseline in log 10 vial load measured at Day 14

Time frame: Day 7 and Day 14

Population: Intent to Treat (ITT) Population (all participants enrolled) with missing values set to zero change

Arm	Measure	Value (MEAN)	Dispersion
Open-Label Ibalizumab Plus OBR	Mean Change in Viral Load as a Measure of Efficacy - ITT-MEF	-1.07 Log10 copies/mL	Standard Deviation 0.618

Secondary

Mean Change in Viral Load as a Measure of Efficacy - Protocol Correct

Mean change from Day 7/Baseline in Log 10 viral load measured at Day 14

Time frame: Day 7 and Day 14

Population: Protocol Correct (PC) Population (all participants with non-missing viral load assessments at Day 14

Arm	Measure	Value (MEAN)	Dispersion
Open-Label Ibalizumab Plus OBR	Mean Change in Viral Load as a Measure of Efficacy - Protocol Correct	-1.11 Log10 copies/mL	Standard Deviation 0.641

Secondary

Proportion of Participants Discontinuing Study Drug Due to Adverse Event

Proportion of participants discontinuing study drug due to occurrence of treatment emergent adverse event

Time frame: Through Week 25/End of Study