Ibalizumab Plus Optimized Background Regimen in Treatment-Experienced Patients With Multi-Drug Resistant HIV-1

• Sponsor: TaiMed Biologics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02707861
• Collaborator: Westat (Other)
• Enrollment: 79
• Locations: 32
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Ibalizumab is a monoclonal antibody that works by blocking HIV entry into the immune system cells (CD4+ or T-cells) the virus typically infects. Ibalizumab is intended for use in combination with other anti-HIV drugs in people with multi-drug resistant HIV and limited treatment options. This study will collect further information on the safety and tolerability of intravenously administered (IV) ibalizumab combined with an optimized background regimen for treating multi-drug resistant HIV-1 infection, and will provide continuing access to ibalizumab for patients completing a prior ibalizumab clinical trial.

Condition or Disease	Intervention/Treatment	Phase
HIV	Drug: ibalizumab; Drug: Optimized Background Regimen	Phase 3

Detailed Description

Participants will enroll into one of two study cohorts. Cohort 1 will provide continued administration of IV ibalizumab for patients completing a prior ibalizumab clinical trial (TaiMed-sponsored or Investigator-Sponsored). Patients will continue to receive IV infusions of ibalizumab at the dosage assigned in the previous study - either 800 mg once every two weeks, or 2000 mg once every four weeks.

Cohort 2 will provide IV ibalizumab, 800 mg once every two weeks, for qualifying patients with multi-drug resistant HIV-1 and limited treatment options who have never previously received ibalizumab.

Participants may continue in this study for 48 weeks, or until ibalizumab becomes commercially available, whichever occurs first.

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Expanded Access Study of Ibalizumab Plus an Optimized Background Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug Resistant (MDR) HIV-1
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Nov 1, 2018
• Actual Study Completion Date: Nov 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available	Drug: ibalizumab; Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry; Other Names: TNX-355, Hu5A8 ; Drug: Optimized Background Regimen; An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).; Other Names: antiretroviral therapy
Experimental: Cohort 2 IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available	Drug: ibalizumab; Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry; Other Names: TNX-355, Hu5A8 ; Drug: Optimized Background Regimen; An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).; Other Names: antiretroviral therapy

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Ibalizumab + OBR [Through 48 weeks]

   Number of participants with Grade 3/4 adverse events possibly, probably, or definitely due to ibalizumab

2. Discontinuations Due to Adverse Events Related to Ibalizumab [48 weeks]

   number of participants discontinuing ibalizumab treatment due to adverse events probably, possibly, or definitely related to ibalizumab

3. Effectiveness of Ibalizumab + OBR (Cohort 2 Only) [7 days]

   Number of patients in Cohort 2 achieving at least a 0.5 log change from Baseline in viral load at Day 7 of the study

Secondary Outcome Measures

1. Suppression to <50 Copies With Ibalizumab + OBR (Cohort 2 Only) [48 weeks]

   Number of patients in Cohort 2 with HIV-1 RNA levels <50 copies/mL at week 48

2. Suppression to <400 Copies by Ibalizumab + OBR (Cohort 2 Only) [48 weeks]

   Number of patients in Cohort 2 with HIV-1 RNA levels <400 copies/mL at week 48

3. Effectiveness of Ibalizumab + OBR by 1.0 Log10 Decrease in Viral Load From Baseline (Cohort 2 Only) [48 weeks]

   Number of patients in Cohort 2 achieving at least a 1.0 log10 decrease in viral load from Baseline measurement at all assessment time points

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

(Cohort 1)

• Currently receiving ibalizumab via other TaiMed-sponsored or investigator-Sponsored protocol

• Are capable of understanding and have voluntarily signed the informed consent document

(Cohort 2)

• 18 years of age or older

• 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

• Are able and willing to comply with all protocol requirements and procedures

• 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 previous viral resistance testing (resistance testing is not provided by the study for qualification purposes)

• Have a history of at least 6 months on antiretroviral treatment

• Are receiving a failing antiretroviral regimen OR have failed and are off therapy

• Have viral sensitivity/susceptibility to at least one antiretroviral agent, other than ibalizumab, as determined by previous resistance test performed within 6 months of screening 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 resistance tests used for screening 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:

(Cohort 1)

• There are no Exclusion Criteria for patients meeting the Inclusion Criteria for Cohort 1

(Cohort 2)

• Eligible for participation in other TaiMed-sponsored clinical trials of ibalizumab

• 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 first administration of investigational medication on this study

• 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 4 weeks before Day 0

• Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)

• Any vaccination within 7 days before Day 0

• 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 on this study

• Any clinically significant Grade 3 or 4 laboratory abnormality according to the Division of AIDS (DAIDS) grading scale, except for the following asymptomatic Grade 3 events:

• triglyceride elevation

• total cholesterol elevation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach Education and Research Consultants	Long Beach	California	United States	90813
2	Southern California Permanente Medical Group	Los Angeles	California	United States	90027
3	Ruane Clinical Research Institute Inc.	Los Angeles	California	United States	90036
4	Charles R. Drew University of Medicine and Science, Clinical and Translational Research Center	Los Angeles	California	United States	90059
5	Anthony Mills MD Inc.	Los Angeles	California	United States	90069
6	Palmtree Clinical Research, Inc.	Palm Springs	California	United States	92262
7	eStudy Site	San Francisco	California	United States	94115
8	Kaiser Foundation Research Institute	San Francisco	California	United States	94118
9	Yale University	New Haven	Connecticut	United States	06510
10	Georgetown University School of Medicine	Washington	District of Columbia	United States	20007
11	Gary Richmond, MD, PA	Fort Lauderdale	Florida	United States	33316
12	AIDS Healthcare Foundation - Kinder Medical Group	Miami	Florida	United States	33133
13	AIDS Healthcare Foundation - South Beach	Miami	Florida	United States	33140
14	Orlando Immunology Center	Orlando	Florida	United States	32803
15	Triple O Research Institute	West Palm Beach	Florida	United States	33401
16	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30312
17	University of Hawaii - John A. Burns School of Medicine	Honolulu	Hawaii	United States	96813
18	Howard Brown Health Center	Chicago	Illinois	United States	60613
19	National Institute of Allergy & Infectious Diseases	Bethesda	Maryland	United States	20892
20	ID Research Institute	Springfield	Massachusetts	United States	01105
21	Central West Clinical Research	Saint Louis	Missouri	United States	63108
22	Jacobi Medical Center	Bronx	New York	United States	10461
23	AIDS Healthcare Foundation - Manhattan Midtown HCC	New York	New York	United States	10001
24	Chelsea Village Medical	New York	New York	United States	10011
25	East Carolina University	Greenville	North Carolina	United States	27834
26	Philadelphia FIGHT	Philadelphia	Pennsylvania	United States	19107
27	St. Jude's Children's Research Hospital	Memphis	Tennessee	United States	38105
28	St. Hope Foundation Community Health Center	Bellaire	Texas	United States	77401
29	North Texas Infectious Disease Consultants	Dallas	Texas	United States	75246
30	Crofoot Research Center	Houston	Texas	United States	77098
31	Research Access Network	Houston	Texas	United States	77098
32	Clinical Research PR, Inc.	San Juan		Puerto Rico	00909

Sponsors and Collaborators

• TaiMed Biologics Inc.
• Westat

Investigators

• Principal Investigator: Stanley T. Lewis, MD, MPH, TaiMed Biologics Inc.

Study Documents (Full-Text)

• Study Protocol - Dec 11, 2017
• Statistical Analysis Plan - Aug 17, 2018

More Information

Publications

None provided.

• Responsible Party: TaiMed Biologics Inc.
• ClinicalTrials.gov Identifier: NCT02707861
• Other Study ID Numbers: TMB-311
• First Posted: Mar 14, 2016
• Last Update Posted: Mar 11, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by TaiMed Biologics Inc.: HIV; Resistant; Salvage; ibalizumab; antibody; AIDS
• Additional relevant MeSH terms: Ibalizumab

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
Period Title: Overall Study
STARTED	41	38
COMPLETED	0	0
NOT COMPLETED	41	38

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Total
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	Total of all reporting groups
Overall Participants	41	38	79
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.8 (9.07)	49.9 (11.7)	51.9 (10.4)
Sex: Female, Male (Count of Participants)
Female	4 9.8%	4 10.5%	8 10.1%
Male	37 90.2%	34 89.5%	71 89.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 29.3%	8 21.1%	20 25.3%
Not Hispanic or Latino	29 70.7%	30 78.9%	59 74.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	12 29.3%	16 42.1%	28 35.4%
White	27 65.9%	20 52.6%	47 59.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 4.9%	2 5.3%	4 5.1%
Region of Enrollment (participants) [Number]
Puerto Rico	2 4.9%	4 10.5%	6 7.6%
United States	39 95.1%	34 89.5%	73 92.4%
Region of Enrollment (participants) [Number]
Puerto Rico	2 4.9%	4 10.5%	6 7.6%
United States	39 95.1%	34 89.5%	73 92.4%
Number of Study Participants Enrolled (Count of Participants)
Count of Participants [Participants]	41 100%	38 100%	79 100%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of Ibalizumab + OBR
Description	Number of participants with Grade 3/4 adverse events possibly, probably, or definitely due to ibalizumab
Time Frame	Through 48 weeks

Outcome Measure Data

Analysis Population Description

intent-to-treat

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
Measure Participants	41	38
Number [participants]	8 19.5%	9 23.7%

2. Primary Outcome

Title	Discontinuations Due to Adverse Events Related to Ibalizumab
Description	number of participants discontinuing ibalizumab treatment due to adverse events probably, possibly, or definitely related to ibalizumab
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

intent-to -treat

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
Measure Participants	41	38
Count of Participants [Participants]	0 0%	3 7.9%

3. Primary Outcome

Title	Effectiveness of Ibalizumab + OBR (Cohort 2 Only)
Description	Number of patients in Cohort 2 achieving at least a 0.5 log change from Baseline in viral load at Day 7 of the study
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

As treated analysis

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
Measure Participants	0	38
Number [participants]	28 68.3%

4. Secondary Outcome

Title	Suppression to <50 Copies With Ibalizumab + OBR (Cohort 2 Only)
Description	Number of patients in Cohort 2 with HIV-1 RNA levels <50 copies/mL at week 48
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

as-treated-population

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
Measure Participants	0	17
Count of Participants [Participants]	11 26.8%

5. Secondary Outcome

Title	Suppression to <400 Copies by Ibalizumab + OBR (Cohort 2 Only)
Description	Number of patients in Cohort 2 with HIV-1 RNA levels <400 copies/mL at week 48
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

as-treated-analysis

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
Measure Participants	0	17
Count of Participants [Participants]	10 24.4%

6. Secondary Outcome

Title	Effectiveness of Ibalizumab + OBR by 1.0 Log10 Decrease in Viral Load From Baseline (Cohort 2 Only)
Description	Number of patients in Cohort 2 achieving at least a 1.0 log10 decrease in viral load from Baseline measurement at all assessment time points
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

as treated analysis

Arm/Group Title	Cohort 1	Cohort 2
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
Measure Participants	0	17
Count of Participants [Participants]	0 0%	11 28.9%

Adverse Events

Time Frame	Adverse event data is reported is reported for all subjects who received at least one dose of ibalizumab. The time period of observation ranges from day 1 to day 869 for study participants depending on the duration of ibalizumab therapy.
Adverse Event Reporting Description	The definitions of adverse events and methods of collection do not differ from clinical trials.gov definitions and methods.
Arm/Group Title	Cohort 1		Cohort 2
Arm/Group Description	IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial OR 2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).		IV ibalizumab (combined with optimized background regimen): 800 mg once every two weeks for qualifying patients who have never received ibalizumab Administered for 48 weeks, or until ibalizumab becomes commercially available ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
All Cause Mortality
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/41 (12.2%)		2/38 (5.3%)
Serious Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/41 (39%)		15/38 (39.5%)
Cardiac disorders
cardiovascular disorder	1/41 (2.4%)	1	1/38 (2.6%)	1
Infections and infestations
sepsis	4/41 (9.8%)	4	4/38 (10.5%)	4
pneumonia	4/41 (9.8%)	4	4/38 (10.5%)	4
opportunistic infection	2/41 (4.9%)	2	2/38 (5.3%)	2
Renal and urinary disorders
acute renal failure	2/41 (4.9%)	2	3/38 (7.9%)	3
Vascular disorders
DVT	3/41 (7.3%)	3	2/38 (5.3%)	2
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/41 (95.1%)		37/38 (97.4%)
Gastrointestinal disorders
diarrhea	17/41 (41.5%)	17	10/38 (26.3%)	10
nausea	8/41 (19.5%)	8	9/38 (23.7%)	9
Nervous system disorders
headache	8/41 (19.5%)	8	10/38 (26.3%)	10
Skin and subcutaneous tissue disorders
rash	17/41 (41.5%)	17	8/38 (21.1%)	8

Limitations/Caveats

This trial included multiple populations- Cohort 1 included subjects who were treated with ibalizumab and OBR on previous trials including TMB-301, TMB-202, and 2 subjects on expanded access. The Cohort 2 subjects were subjects with MDR resistant virus who were treated with OBR plus ibalizumab. No subjects completed the planned duration of study as the vast majority were switched to commercial supply of drug when the drug was approved by USFDA.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.