HIVPhase 2TMB-202NCT00784147
Dose-Response Study of Ibalizumab (Monoclonal Antibody) Plus Optimized Background Regimen in Patients With HIV-1
A Phase 2 study testing Ibalizumab in people with HIV, run by TaiMed Biologics Inc. at 30 sites in 2 countries.
Trial summary
The investigational product, ibalizumab, is a humanized IgG4 monoclonal antibody administered via intravenous infusion at 800 mg every 2 weeks or at 2000 mg every 4 weeks. In addition to study drug, all patients will receive an optimized background regimen (OBR), which is a standard-of-care regimen selected by the… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- HIV
- What is being tested?
- Ibalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 113 participants
- Where
- 30 sitesin 2 countries
- Study dates
- Aug 2008to Apr 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Are capable of understanding and have voluntarily signed the informed consent document
- Have documented HIV-1 infection by official, signed, written history (eg, 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
- Are 18 years of age or older
- Have a life expectancy that is >6 months.
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- Have a viral load >1,000 copies/mL and documented decreased susceptibility to at least one NRTI, one NNRTI, and one PI, as measured by resistance testing
- Are receiving a stable highly active antiretroviral regimen for at least 8 weeks before screening and are willing to continue that regimen until the baseline visit, OR (in the past 8 weeks) have failed and are off therapy and are willing to stay off therapy until the baseline visit
- Have viral sensitivity/susceptibility to at least one agent (OSS criteria) 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 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
Who cannot join
- Any active AIDS-defining illness per Category C conditions according to the Center for Disease Control (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 (ie, 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 randomization
- Any investigational therapy within 30 days before randomization, except for HIV-agents available in expanded-access programs
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- Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)
- Any vaccination within 21 days before randomization
- Any female patient who either is pregnant, intends to become pregnant, or is currently breast-feeding
- 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 toxicity according to the Division of AIDS grading scale, except for the following asymptomatic grade 3 events: triglyceride elevation \& total cholesterol elevation
Trial locations and contacts
30 sites in 2 countries.
30 sites in 2 countries
United States28 sites
South Florida Clinical Research
Atlantis, Florida, 33462
Central Texas Clinical Research
Austin, Texas, 78705
AIDS Health Care Foundation - Research
Beverly Hills, California, 90211
Northstar Medical Center
Chicago, Illinois, 60657
North Texas Infectious Disease Consultants
Dallas, Texas, 75246
Kaiser Permanente of Colorado
Denver, Colorado, 80205
National Jewish Medical & Research Center
Denver, Colorado, 80206
The Brody School of Medicine at ECU
Greenville, North Carolina, 27834
Valley AIDS Council
Harlingen, Texas, 78550
Therapeutic Concepts
Houston, Texas, 77004
University of Texas Health Science Center
Houston, Texas, 77030
Nationsmed Clinical Research
Houston, Texas, 77036
Dr. Gordon E. Crofoot, MD, PA
Houston, Texas, 77098
Research Access Network
Houston, Texas, 77098
Indiana University School of Medicine - Wishard Memorial Hospital
Indianapolis, Indiana, 46202
Living Hope Clinical Foundation
Long Beach, California, 90813
Kaiser Permanente Medical Center
Los Angeles, California, 90027
University of Miami, Miller School of Medicine
Miami, Florida, 33136
AIDS Community Research Initiative of America
New York, New York, 10018
St. Michael's Medical Center
Newark, New Jersey, 07102
Orlando Immunology Center
Orlando, Florida, 32802
Associates in Infectious Diseases
Port Saint Lucie, Florida, 34952
The Research & Educational Group
Portland, Oregon, 97210
Quest Clinical Research
San Francisco, California, 94115
Kaiser Permanente Medical Center Research Unit
San Francisco, California, 94118
Treasure Coast Infectious Disease Consultants
Vero Beach, Florida, 32960
Whitman-Walker Clinic
Washington D.C., District of Columbia, 20009
Triple O Medical Services, Inc.
West Palm Beach, Florida, 33401
Puerto Rico2 sites
Clinical Research Puerto Rico
San Juan, 00909
HOPE Clinical Research
San Juan, 00909
About this study
Official title: A Phase 2b, Randomized, Double-Blinded, 48-Week, Multicenter, Dose-Response Study of Ibalizumab Plus an Optimized Background Regimen in Treatment-Experienced Patients Infected With HIV-1(Amended to 24-Weeks)
The investigational product, ibalizumab, is a humanized IgG4 monoclonal antibody administered via intravenous infusion at 800 mg every 2 weeks or at 2000 mg every 4 weeks. In addition to study drug, all patients will receive an optimized background regimen (OBR), which is a standard-of-care regimen selected by the investigator prior to randomization that is comprised of 2-4 antiretroviral agents. These agents must have been approved by the local regulatory agency or be available through expanded-access programs for treatment of human immunodeficiency virus (HIV).
Read the detailed description
The primary objectives of this study are to:
- Evaluate the dose-response relationship of antiviral activity of the ibalizumab dose regimens at Week 24 in order to determine the optimal dose and regimen. The primary evaluation of effectiveness will be based on the proportion of patients achieving undetectable viral loads at Week 24.
- Evaluate the safety and tolerability of two dose regimens of ibalizumab for dose selection
The secondary objectives of this study are to:
- Evaluate changes from Baseline in viral load, CD4+ cell counts, and time to loss of virologic response (TLOVR)
- Characterize HIV-1 sensitivity/susceptibility changes associated with ibalizumab administration in combination with OBR
- Determine the presence and significance of anti-ibalizumab antibodies, if any (immunogenicity of ibalizumab)
- Assess CD4 receptor density and occupancy
- Determine the impact of ibalizumab on quality of life as assessed by patient-reported outcomes on questionnaires
- Evaluate the pharmacokinetic profile of two dose regimens of ibalizumab at steady state
- Conditions
- HIV
- Being tested
- Ibalizumab
- Keywords
- HIV, CD4, experienced, resistant, resistance, monoclonal, antibody, infusion, ibalizumab, TNX355, TNX-355, TMB355, TMB-355
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbalizumabDrug
Also called TNX-355; Hu5A8
Ibalizumab 800 mg IV every 2 weeks
IbalizumabDrug
Also called TNX-355; Hu5A8
Ibalizumab 2000 mg IV every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ibalizumab 800 mg | Active comparator | every 2 weeks, combined with an Optimized Background Regimen Receives: Drug: Ibalizumab |
| Ibalizumab 2000 mg | Active comparator | every 4 weeks, combined with an Optimized Background Regimen Receives: Drug: Ibalizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Proportion of Patients Achieving Undetectable Viral Loads at Week 24.
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.
Measured: 24 weeks
Secondary outcomes (2)
Mean Change From Baseline in Viral Load (log10) at Week 24/EOS
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.
Measured: Week 24 / End of Study
Mean Change From Baseline in CD4+ T-Cell Count at Week 24/EOS
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.
Measured: Week 24 / End of Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2008 (estimated)
- Study startAug 2008
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- TaiMed Biologics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stanley T. Lewis, MD, Study director, TaiMed Biologics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00784147
- Sponsor's protocol ID
- TMB-202 Amendment 2
- Acronym
- TMB-202
- Status last verified
- Apr 2014
- First submitted
- 30 Oct 2008
- Last updated
- 5 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b, Randomized, Double-Blinded, 48-Week, Multicenter, Dose-Response Study of Ibalizumab Plus an Optimized Background Regimen in Treatment-Experienced Patients Infected With HIV-1(Amended to 24-Weeks)
- ClinicalTrials.gov ID
- NCT00784147
- Acronym / sponsor ID
- TMB-202 / TMB-202 Amendment 2
- Conditions
- HIV
- Keywords
- HIV, CD4, experienced, resistant, resistance, monoclonal, antibody, infusion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- TaiMed Biologics Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 3 Nov 2008 (estimated)
- Results
- Posted 17 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigational product, ibalizumab, is a humanized IgG4 monoclonal antibody administered via intravenous infusion at 800 mg every 2 weeks or at 2000 mg every 4 weeks. In addition to study drug, all patients will receive an optimized background regimen (OBR), which is a standard-of-care regimen selected by the investigator prior to randomization that is comprised of 2-4 antiretroviral agents. These agents must have been approved by the local regulatory agency or be available through expanded-access programs for treatment of human immunodeficiency virus (HIV).
Detailed description
The primary objectives of this study are to:
- Evaluate the dose-response relationship of antiviral activity of the ibalizumab dose regimens at Week 24 in order to determine the optimal dose and regimen. The primary evaluation of effectiveness will be based on the proportion of patients achieving undetectable viral loads at Week 24.
- Evaluate the safety and tolerability of two dose regimens of ibalizumab for dose selection
The secondary objectives of this study are to:
- Evaluate changes from Baseline in viral load, CD4+ cell counts, and time to loss of virologic response (TLOVR)
- Characterize HIV-1 sensitivity/susceptibility changes associated with ibalizumab administration in combination with OBR
- Determine the presence and significance of anti-ibalizumab antibodies, if any (immunogenicity of ibalizumab)
- Assess CD4 receptor density and occupancy
- Determine the impact of ibalizumab on quality of life as assessed by patient-reported outcomes on questionnaires
- Evaluate the pharmacokinetic profile of two dose regimens of ibalizumab at steady state
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ibalizumab 800 mg | Active comparator | Drug: Ibalizumabevery 2 weeks, combined with an Optimized Background Regimen |
| Ibalizumab 2000 mg | Active comparator | Drug: Ibalizumabevery 4 weeks, combined with an Optimized Background Regimen |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Are capable of understanding and have voluntarily signed the informed consent document
- Have documented HIV-1 infection by official, signed, written history (eg, 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
- Are 18 years of age or older
Key exclusion criteria (13 listed)
- Any active AIDS-defining illness per Category C conditions according to the Center for Disease Control (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 (ie, 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 randomization
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbalizumabAlso: TNX-355; Hu5A8Ibalizumab 800 mg IV every 2 weeks | Drug | Ibalizumab 800 mg |
| IbalizumabAlso: TNX-355; Hu5A8Ibalizumab 2000 mg IV every 4 weeks | Drug | Ibalizumab 2000 mg |
Primary outcome
The Proportion of Patients Achieving Undetectable Viral Loads at Week 24.
Time frame: 24 weeks
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.
2 secondary outcomes
Mean Change From Baseline in Viral Load (log10) at Week 24/EOS
Time frame: Week 24 / End of Study
Mean Change From Baseline in CD4+ T-Cell Count at Week 24/EOS
Time frame: Week 24 / End of Study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stanley T. Lewis, MD study director
TaiMed Biologics Inc.
30 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibalizumab in people with HIV, run by TaiMed Biologics Inc. at 30 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Proportion of Patients Achieving Undetectable Viral Loads at Week 24. (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2014.