What is an investigational drug?
An investigational drug is one that is under study and is not approved by the U.S. Food and Drug Administration (FDA) for sale in the United States. Medical research studies are conducted to evaluate the safety and effectiveness of an investigational drug. These research studies are also called clinical trials. Once an investigational drug has been proven safe and effective in clinical trials, FDA may approve the drug for sale in the United States.
What is ibalizumab?
Ibalizumab is an investigational drug that is being studied for the treatment and prevention of HIV infection.5
Ibalizumab belongs to a class (group) of HIV drugs called entry and fusion inhibitors.2 Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.
Ibalizumab works by attaching to a protein on the surface of the immune cells. The protein is called the CD4 receptor. When ibalizumab attaches to the CD4 receptor, HIV cannot attach to, enter, or infect the cell.6
How are clinical trials of investigational drugs conducted?
Clinical trials are conducted in phases. Each phase has a different purpose and helps researchers answer different questions.7
- Phase I trials: Researchers test an investigational drug in a small group of people (20–80) for the first time. The purpose is to evaluate its safety and identify side effects.
- Phase II trials: The investigational drug is administered to a larger group of people (100–300) to determine its effectiveness and to further evaluate its safety.
- Phase III trials: The investigational drug is administered to large groups of people (1,000–3,000) to confirm its effectiveness, monitor side effects, compare it with standard or equivalent treatments, and collect information that will allow the investigational drug to be used safely.7
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase III clinical trial to be considered for approval by FDA for sale in the United States. Some drugs go through FDA’s accelerated approval process and are approved before a Phase III clinical trial is complete. After a drug is approved by FDA and made available to the public, researchers track its safety in Phase IV trials to seek more information about the drug’s risks, benefits, and optimal use.7
In what phase of testing is ibalizumab?
Ibalizumab is currently being studied in a Phase III clinical trial.4
Expanded access to ibalizumab may be available to patients who qualify for compassionate use treatment. (More details can be found on ClinicalTrials.gov [NCT02028819].)3
What are some studies on ibalizumab?
Study Name: TMB-202; NCT00784147
Location: Multiple sites, including sites located in the United States
- HIV-infected adults whose HIV did not respond to at least one HIV medicine from each of the following three drug classes: nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI).
- All participants had taken HIV medicines before entering the study (treatment-experienced). Participants were either (1) on antiretroviral therapy (ART) for at least 8 weeks before entering the study or (2) had treatment failure within the past 8 weeks before entering the study and were off therapy. (Treatment failure is when an ART regimen is unable to control HIV infection.)
: The purpose of this study was to look at the safety and antiviral activity of ibalizumab that was given as part of two different dosing regimens.
: Participants were in one of the following treatment groups for 24 weeks: (1) 800 mg of intravenous (IV) ibalizumab every 2 weeks or (2) 2000 mg of IV ibalizumab every 4 weeks. (An IV injection is placed directly into a vein.) Study participants also received an optimized background regimen. (An optimized background regimen is a combination of drugs, chosen on the basis of a person’s resistance test results and treatment history, that are not being studied as the investigational drug[s] in the clinical trial, but are given to help control a participant’s HIV infection.) No control arm was used in this study.
- Both ibalizumab dosing regimens resulted in significant antiviral activity in treatment-experienced adults.
- In terms of safety, there were no serious side effects among participants. None of the participants stopped the study because of side effects, and there were no “clinically relevant” effects on participants' vital signs or laboratory values.
- The most common side effects were rash, diarrhea, headache, and nausea.8,9
: Participants who had a successful antiviral response to ibalizumab in Study TMB-202 could choose to extend their treatment of ibalizumab plus an optimized background regimen beyond 24 weeks under a separate study protocol (NCT01056393).10
: TMB-301; NCT02475629
: Not available
- HIV-infected adults whose HIV has not responded to at least one HIV medicine from each of three HIV drug classes.
- All participants are treatment-experienced and must have been on an ART for at least 6 months. Participants are either (1) currently on an ART regimen and experiencing treatment failure or (2) had treatment failure within the 8 weeks before entering the study and are off therapy.
: The purpose of this study is to look at the safety and effectiveness of ibalizumab.
: This study will involve only one group of participants. The study will be divided into the following three time periods:
- Period 1: Initially, participants will be monitored as they continue on a “failing“ ART regimen or as they continue on no HIV medicines (whichever they were doing when they started the study).
- Period 2: On Day 7, all participants will receive a single IV dose of 2000 mg of ibalizumab. They will continue with their failing ART regimen or continue with no other HIV medicines.
- Period 3: On Day 14, participants will begin an optimized background regimen. Then on Day 21, participants will receive 800 mg of IV ibalizumab every 2 weeks through Week 23.
* TMB-301 is currently planned to take place, and results are not yet available.4
A subcutaneous (SC) injection form of ibalizumab has also been studied in a Phase I trial (NCT01292174). (An SC injection is placed under the skin.) This study looked at the safety and drug properties of ibalizumab given by SC injection to at-risk, HIV-uninfected adults. Results from the study support further research of SC ibalizumab for HIV treatment or as prevention medicine.11,12
What side effects might ibalizumab cause?
In the Phase IIb study (NCT00784147) discussed under the previous question, the most common side effects reported were the following: rash, diarrhea, headache, and nausea. Most side effects were considered mild to moderate.8
Because ibalizumab is still being studied, information on possible side effects of the drug is not complete. As testing of ibalizumab continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying ibalizumab?
More information about ibalizumab-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.
I am interested in participating in a clinical trial of ibalizumab. How can I find more information about participating in a clinical trial?
Participating in a clinical trial can provide benefits. For example, a volunteer participant can benefit from new research treatments before they are widely available. Participants also receive regular and careful medical attention from a research team that includes doctors and other health professionals. However, clinical trials may also involve risks of varying degrees, such as unpleasant, serious, or even life-threatening side effects from the treatment being studied.7
Your health care provider can help you decide whether participating in a clinical trial is right for you. For more information, visit NIH Clinical Research Trials and You.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: http://chem.sis.nlm.nih.gov/chemidplus/rn/680188-33-4. Last accessed on September 7, 2015.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on September 7, 2015.
- University of Colorado, Denver. Compassionate Use of Ibalizumab for the Treatment of HIV Infection. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 3, 2014. NLM Identifier: NCT02028819. Available at: http://www.clinicaltrials.gov/ct2/show/NCT02028819. Last accessed on September 7, 2015.
- TaiMed Biologics Inc. 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. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 11, 2015. NLM Identifier: NCT02475629. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02475629. Last accessed on September 7, 2015.
- Pace CS, Fordyce MW, Franco D, Kao CY, Seaman MS, Ho DD. Anti-CD4 monoclonal antibody ibalizumab exhibits breadth and potency against HIV-1, with natural resistance mediated by the loss of a V5 glycan in envelope. J Acquir Immune Defic Syndr. 2013 Jan 1;62(1):1-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23023102. Last accessed on September 7, 2015.
- Song R, Franco D, Kao CY, Yu F, Huang Y, Ho DD. Epitope Mapping of Ibalizumab, a Humanized Anti-CD4 Monoclonal Antibody with Anti-HIV-1 Activity in Infected Patients. J Virol. 2010 Jul;84(14):6935-42. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898252. Last accessed on September 7, 2015.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You.
Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on September 7, 2015.
- Khanlou H, Gathe J Jr, Schrader S, Towner W, Weinheimer S, Lewis S. Safety, Efficacy, and Pharmacokinetics of Ibalizumab in Treatment-Experienced HIV-1 Infected Patients: a Phase 2b Study. Abstract presented at: 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2011; Chicago, IL. Abstract H2-794b. Available at: http://abstractsonline.com/Plan/ViewAbstract.aspx?sKey=553b562f-106a-48ff-b263-3cf82d20946e&cKey=214ca279-ad2f-4c51-8226-6747ca35bbab&mKey=%7b0C918954-D607-46A7-8073-44F4B537A439%7d. Last accessed on September 7, 2015.
- TaiMed Biologics Inc. 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). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 30, 2008. NLM Identifier: NCT00784147. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00784147. Last accessed on September 7, 2015.
- Kaiser Permanente. Investigator-Sponsored Protocol - Continued Use of Ibalizumab. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 22, 2010. NLM Identifier: NCT01056393. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01056393. Last accessed on September 7, 2015.
- TaiMed Biologics Inc. A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, Sequential Dose-Escalation Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneously Administered Ibalizumab in HIV-Negative, At-Risk Volunteers. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 7, 2011. NLM Identifier: NCT01292174. Available at: http://www.clinicaltrials.gov/ct2/show/NCT01292174. Last accessed on September 7, 2015.
- Ernst J, Keefer M, Lalezari J, et al. Subcutaneous Ibalizumab in At-Risk Healthy Subjects. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 5-9, 2014; Washington, DC. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2014. Available at: http://www.natap.org/2014/ICAAC/ICAAC_21.htm. Last accessed on September 7, 2015.
Last Reviewed: September 7, 2015