Trial Outcomes & Findings for Dose-Response Study of Ibalizumab (Monoclonal Antibody) Plus Optimized Background Regimen in Patients With HIV-1 (NCT NCT00784147)

Last Updated: 2014-05-05

Results Overview

For the primary efficacy analysis, "undetectable" was defined as having HIV-1 RNA below the limit of assay detection at \<50 copies/mL. The primary efficacy endpoint was analyzed using Fisher exact test. The primary analysis was performed using the ITT population and both the missing data equals treatment failure (MEF) and last observation carried forward (LOCF) methods. The more conservative MEF results are recorded here.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

113 participants

Primary outcome timeframe

24 weeks

Results posted on

2014-05-05

Participant Flow

Over the period from late 2008 through early 2010, a total of 113 patients were enrolled into the study from 35 study sites in the United States and Taiwan. The study sites were private medical practices, not-for-profit community clinics and university hospital clinics delivering HIV primary care.

Participant milestones

Participant milestones
Measure	Ibalizumab 800 mg every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Overall Study STARTED	59	54
Overall Study COMPLETED	51	45
Overall Study NOT COMPLETED	8	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Ibalizumab 800 mg every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Overall Study Lost to Follow-up	2	4
Overall Study Withdrawal by Subject	1	3
Overall Study Physician Decision	2	1
Overall Study Protocol Violation	1	1
Overall Study Death	2	0

Baseline Characteristics

Dose-Response Study of Ibalizumab (Monoclonal Antibody) Plus Optimized Background Regimen in Patients With HIV-1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibalizumab 800 mg n=59 Participants every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 Participants every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks	Total n=113 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	58 Participants n=5 Participants	54 Participants n=7 Participants	112 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	48.3 years n=5 Participants	47.9 years n=7 Participants	48.1 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	50 Participants n=7 Participants	101 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	28 Participants n=7 Participants	70 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
HIV-1 RNA (viral load)	114,675.3 copies/mL n=5 Participants	136,452.8 copies/mL n=7 Participants	125,082.2 copies/mL n=5 Participants
CD4+ T-cell count	106.4 cells/mL STANDARD_DEVIATION 91.3 • n=5 Participants	112.4 cells/mL STANDARD_DEVIATION 118.5 • n=7 Participants	109.3 cells/mL STANDARD_DEVIATION 104.7 • n=5 Participants
Number of active agents in OBR	1.9 Pharmaceutical Agents STANDARD_DEVIATION 0.8 • n=5 Participants	1.8 Pharmaceutical Agents STANDARD_DEVIATION 0.7 • n=7 Participants	1.8 Pharmaceutical Agents STANDARD_DEVIATION 0.7 • n=5 Participants
Time from initial documented HIV infection	17.0 years STANDARD_DEVIATION 4.4 • n=5 Participants	16.9 years STANDARD_DEVIATION 6.2 • n=7 Participants	17.0 years STANDARD_DEVIATION 5.4 • n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Outcome measures

Outcome measures
Measure	Ibalizumab 800 mg n=59 Participants every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 Participants every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
The Proportion of Patients Achieving Undetectable Viral Loads at Week 24.	44 percentage of participants	28 percentage of participants

SECONDARY outcome

Timeframe: Week 24 / End of Study

The mean change in HIV-1 RNA (log10) from the Baseline measurement was analyzed at Week 24/End of Study using a generalized linear model at each scheduled study visit.

Outcome measures

Outcome measures
Measure	Ibalizumab 800 mg n=59 Participants every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 Participants every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Mean Change From Baseline in Viral Load (log10) at Week 24/EOS	-1.6 log10 copies/mL Standard Deviation 1.3	-1.5 log10 copies/mL Standard Deviation 1.4

SECONDARY outcome

Timeframe: Week 24 / End of Study

The mean change in CD4+ T-cell count from the Baseline measurement at Week 24/End of Study was summarized at each scheduled time point by treatment group.

Outcome measures

Outcome measures
Measure	Ibalizumab 800 mg n=59 Participants every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 Participants every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Mean Change From Baseline in CD4+ T-Cell Count at Week 24/EOS	36.5 cell/mL Standard Deviation 63.0	39.8 cell/mL Standard Deviation 80.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24

This measure was assessed in the same manner as the primary efficacy analysis for the proportion of patients achieving HIV-1 RNA levels below 200 copies/mL at Week 24 of the study.

Outcome measures

Outcome measures
Measure	Ibalizumab 800 mg n=59 Participants every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 Participants every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Proportion of Patients With Viral Load <200 Copies/mL at Week 24	53 percentage of patients	43 percentage of patients

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24

This efficacy measure was assessed in the same manner as the primary efficacy analysis to determine the proportion of the total population achieving HIV-1 RNA levels \<400 copies at Week 24 of the study.

Outcome measures

Outcome measures
Measure	Ibalizumab 800 mg n=59 Participants every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 Participants every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Proportion of Patients With Viral Load <400 Copies/mL at Week 24	58 percentage of patients	46 percentage of patients

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24

This efficacy assessment was performed in the same manner as the primary efficacy analysis for the proportion of the total population achieving at least a 1.0 log10 reduction from Baseline in HIV-1 RNA.

Outcome measures

Outcome measures
Measure	Ibalizumab 800 mg n=59 Participants every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 Participants every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Proportion of Patients With a 1.0 log10 or Greater Reduction in Viral Load at Week 24	63 percentage of patients	59 percentage of patients

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 24

This efficacy assessment was performed in the same manner as the primary efficacy analysis for the proportion of the total population achieving at least a 0.5 log10 reduction from the Baseline measurement in HIV-1 RNA at Week 24 of the study.

Outcome measures

Outcome measures
Measure	Ibalizumab 800 mg n=59 Participants every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 Participants every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Proportion of Patients With a 0.5 log10 or Greater Reduction in Viral Load at Week 24	68 percentage of patients	59 percentage of patients

Adverse Events

Ibalizumab 800 mg

Serious events: 7 serious events

Other events: 46 other events

Deaths: 0 deaths

Ibalizumab 2000 mg

Serious events: 3 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ibalizumab 800 mg n=59 participants at risk every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 participants at risk every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	0.00% 0/54 • Through Week 24 of the Study
Renal and urinary disorders Acute Renal Failure	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	0.00% 0/54 • Through Week 24 of the Study
Gastrointestinal disorders Gastroenteritis	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	0.00% 0/54 • Through Week 24 of the Study
Injury, poisoning and procedural complications Road Traffic Accident	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	0.00% 0/54 • Through Week 24 of the Study
Nervous system disorders Paraesthesias	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	0.00% 0/54 • Through Week 24 of the Study
Infections and infestations Cerebral Toxoplasmosis	0.00% 0/59 • Through Week 24 of the Study	1.9% 1/54 • Number of events 1 • Through Week 24 of the Study
Infections and infestations CMV Viremia	0.00% 0/59 • Through Week 24 of the Study	3.7% 2/54 • Number of events 3 • Through Week 24 of the Study
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	0.00% 0/54 • Through Week 24 of the Study
Immune system disorders End-stage AIDS	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	0.00% 0/54 • Through Week 24 of the Study

Other adverse events

Other adverse events
Measure	Ibalizumab 800 mg n=59 participants at risk every 2 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 800 mg IV every 2 weeks	Ibalizumab 2000 mg n=54 participants at risk every 4 weeks, combined with an Optimized Background Regimen Ibalizumab : Ibalizumab 2000 mg IV every 4 weeks
Skin and subcutaneous tissue disorders Rash	8.5% 5/59 • Number of events 5 • Through Week 24 of the Study	16.7% 9/54 • Number of events 9 • Through Week 24 of the Study
Gastrointestinal disorders Diarrhea	5.1% 3/59 • Number of events 3 • Through Week 24 of the Study	11.1% 6/54 • Number of events 6 • Through Week 24 of the Study
Gastrointestinal disorders Nausea	3.4% 2/59 • Number of events 2 • Through Week 24 of the Study	13.0% 7/54 • Number of events 7 • Through Week 24 of the Study
Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Infection	6.8% 4/59 • Number of events 4 • Through Week 24 of the Study	5.6% 3/54 • Number of events 3 • Through Week 24 of the Study
General disorders Headache	3.4% 2/59 • Number of events 2 • Through Week 24 of the Study	7.4% 4/54 • Number of events 4 • Through Week 24 of the Study
General disorders Fatigue	5.1% 3/59 • Number of events 3 • Through Week 24 of the Study	5.6% 3/54 • Number of events 3 • Through Week 24 of the Study
Respiratory, thoracic and mediastinal disorders Cough	10.2% 6/59 • Number of events 6 • Through Week 24 of the Study	0.00% 0/54 • Through Week 24 of the Study
Infections and infestations Oral Candidiasis	3.4% 2/59 • Number of events 2 • Through Week 24 of the Study	7.4% 4/54 • Number of events 4 • Through Week 24 of the Study
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	3.4% 2/59 • Number of events 2 • Through Week 24 of the Study	5.6% 3/54 • Number of events 3 • Through Week 24 of the Study
General disorders Dizziness	6.8% 4/59 • Number of events 4 • Through Week 24 of the Study	1.9% 1/54 • Number of events 1 • Through Week 24 of the Study
Gastrointestinal disorders Vomiting	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	5.6% 3/54 • Number of events 3 • Through Week 24 of the Study
Respiratory, thoracic and mediastinal disorders Sinusitis	3.4% 2/59 • Number of events 2 • Through Week 24 of the Study	3.7% 2/54 • Number of events 2 • Through Week 24 of the Study
Skin and subcutaneous tissue disorders Folliculitis	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	5.6% 3/54 • Number of events 3 • Through Week 24 of the Study
Musculoskeletal and connective tissue disorders Low Back Pain	3.4% 2/59 • Number of events 2 • Through Week 24 of the Study	3.7% 2/54 • Number of events 2 • Through Week 24 of the Study
Skin and subcutaneous tissue disorders Dermatitis	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	3.7% 2/54 • Number of events 2 • Through Week 24 of the Study
General disorders Chills	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	3.7% 2/54 • Number of events 2 • Through Week 24 of the Study
Eye disorders Conjunctivitis	1.7% 1/59 • Number of events 1 • Through Week 24 of the Study	3.7% 2/54 • Number of events 2 • Through Week 24 of the Study
Skin and subcutaneous tissue disorders Injection Site Reaction	3.4% 2/59 • Number of events 2 • Through Week 24 of the Study	1.9% 1/54 • Number of events 1 • Through Week 24 of the Study
Respiratory, thoracic and mediastinal disorders Rhinitis Allergic	3.4% 2/59 • Number of events 2 • Through Week 24 of the Study	1.9% 1/54 • Number of events 1 • Through Week 24 of the Study

Additional Information

Stanley T. Lewis, Jr., MD

TaiMed Biologics, Inc.

Phone: 949-769-6543

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60