Drugs

Ibalizumab

Ibalizumab

Other Names: Hu5A8, IBA, TMB-355, TNX-355 Drug Class: Entry Inhibitor Registry Number: 680188-33-4 (CAS) Chemical Name: Immunoglobulin G4, anti-(human CD4 (antigen)) (human-mouse monoclonal 5A8 γ4-chain), disulfide with human-mouse monoclonal 5A8 κ-chain, dimer Organization: TaiMed Biologics Phase of Development: Ibalizumab is in Phase III development. An application for marketing approval of ibalizumab for the treatment of multidrug-resistant HIV was submitted to the U.S. Food and Drug Administration in May 2017.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and TaiMed Biologics news release3)

What is an investigational drug?

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.

To learn more about investigational drugs, read the AIDSinfo What is an Investigational HIV Drug? fact sheet.

What is ibalizumab?

What is ibalizumab?

Ibalizumab is an investigational drug that is being studied for the treatment and prevention of HIV infection.4

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.5

How are clinical trials of investigational drugs conducted?

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.6

  • 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.6

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.6

Some clinical trials are categorized as “a” or “b,” such as “Phase Ia” or “Phase IIb.” These different subphases typically mean that a study is researching certain types of information or using a certain type of participant population.

In what phase of testing is ibalizumab?

In what phase of testing is ibalizumab?

Ibalizumab is currently being studied in a Phase III clinical trial.2

What are some studies on ibalizumab?

What are some studies on ibalizumab?

Study Name: TNX-355.03; NCT00089700
Sponsor: Tanox
Phase: IIa
Status: This study has been completed.
Location: United States, Canada, and Puerto Rico
Participants:

  • Participants were adults with HIV who had been on antiretroviral therapy (ART) for at least 6 months before starting the study. (ART is the recommended treatment for HIV infection and involves using a combination of different HIV medicines to prevent HIV from multiplying.)
  • At some point while on ART, participants had taken a nucleoside reverse transcriptase inhibitor (NRTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI).
  • Participants were either (1) on an ART regimen and experiencing treatment failure at the start of the study or (2) had experienced treatment failure within the 8 weeks before entering the study. (Treatment failure is when an ART regimen is unable to control HIV infection.)
  • Participants had viral load levels of 10,000 copies/mL within 8 weeks of starting the study. (Viral load is the amount of HIV in a blood sample.)
  • Participants had CD4 counts of 50 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells in a sample of blood and is an important indicator of immune function.)
Purpose: The purpose of this study was to determine the safety and effectiveness of ibalizumab when compared to a placebo. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)7,8


Study Names: TMB-202; NCT00784147
Sponsor: TaiMed Biologics Inc.
Phase: IIb
Status: This study has been completed.
Location: United States and Puerto Rico
Participants
  • Participants were adults with HIV who had been on ART before starting the study. Participants either (1) were on ART for at least 8 weeks before entering the study or (2) had treatment failure within the 8 weeks before entering the study and were off ART.
  • Participants’ HIV had not responded to at least 1 HIV medicine from each of the following 3 drug classes: NRTIs, NNRTIs, and PIs. 
  • Testing showed that at least 1 HIV medicine would work against the participant’s HIV.
  • Participants had viral load levels of at least 1,000 copies/mL.
Purpose: The purpose of this study was to look at the safety, tolerability, and antiviral activity of 2 different dosing regimens of ibalizumab and to determine the best dose.9,10 
Note: Participants who had a successful antiviral response to ibalizumab in Study TMB-202 could choose to extend their treatment regimen of ibalizumab plus an optimized background regimen beyond 24 weeks under a separate study protocol (NCT01056393). (An optimized background regimen is a combination of drugs that are not being studied as the investigational drug in the clinical trial but are given to help control a participant’s HIV infection. The drugs in an optimized background regimen are chosen on the basis of a person’s resistance test results and treatment history.)11


Study Names: TMB-301; NCT02475629
Sponsor: TaiMed Biologics Inc.
Phase: III
Status: This study has been completed.
Location: United States, Puerto Rico, and Taiwan
Participants
  • Participants were adults with HIV whose HIV had not responded to at least 1 HIV medicine from each of 3 HIV drug classes.
  • Participants had a type of HIV that could be treated with at least 1 additional ARV drug other than ibalizumab.
  • Participants had a viral load levels greater than 1,000 copies/mL.
  • All participants had a history of at least 6 months on ART. Participants either (1) were on an unchanged ART regimen for at least 8 weeks before study entry and were experiencing treatment failure or (2) had experienced treatment failure within the 8 weeks before entering the study and were off therapy at the time of study entry.
Purpose: The purpose of this study was to look at the safety and effectiveness of ibalizumab.12


Study Names: TMB-311; NCT02707861
Sponsor: TaiMed Biologics Inc.
Phase: III
Status: This study is currently recruiting participants.
Location: United States and Puerto Rico
Participants: This study involves 2 groups of participants:
  • One group has already completed a previous ibalizumab clinical trial.
  • The other group includes adults with HIV who have taken ART before but have never taken ibalizumab before. Participants in this group have a viral load greater than 1,000 copies/mL. They were on ART for at least 6 months and are currently on a failing ART regimen or have had treatment failure in the past and are off ART now.
  • Participants have a type of HIV that can be treated by at least 1 additional antiretroviral drug other than ibalizumab.

Purpose: The purpose of this study is to investigate the safety and tolerability of ibalizumab. The study will also provide access to ibalizumab for people with multidrug-resistant HIV who have previously taken ibalizumab.13

For more details on the studies listed above, see the Health Professional version of this information.

A subcutaneous (SC) injection form of ibalizumab was 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 adults without HIV who were at risk of becoming infected with HIV. Results from the study support further research of SC ibalizumab for HIV treatment or as prevention medicine.14,15 An intramuscular(IM) form of ibalizumab was studied in a Phase I/II trial. The study looked at the drug properties, safety, and effectiveness of IM ibalizumab in participants with HIV.16

What side effects might ibalizumab cause?

What side effects might ibalizumab cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in studies of ibalizumab discussed under the previous question.

TMB-202 (NCT00784147):

In this Phase IIb study, the most common side effects reported were the following: rash, diarrhea, headache, and nausea. Most side effects were considered mild to moderate.9,17

TMB-301 (NCT02475629):

During the first 2 weeks of this Phase III study, side effects included dizziness, weakness, fatigue, nausea, vomiting, and rash. At the end of the study (Week 24), researchers reported that most of the side effects were mild to moderate in intensity. One participant had immune reconstitution inflammatory syndrome (IRIS), which was related to ibalizumab and caused the participant to stop the study early.12,18,19

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?

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.

How can I find more information about participating in a clinical trial?

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.6

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.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.sis.nlm.nih.gov/chemidplus/rn/680188-33-4. Last accessed on November 3, 2017.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on November 3, 2017.
  3. TaiMed Biologics: News Release, dated May 4, 2017. TaiMed submits biologics license application for HIV monoclonal antibody and long-acting investigational antiretroviral ibalizumab. Available at: http://www.taimedbiologics.com/news/info/58. Last accessed on November 3, 2017.
  4. 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 November 3, 2017.
  5. 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 November 3, 2017.
  6. National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: https://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on November 3, 2017.
  7. Tanox. A Phase 2, Multicenter, randomized, double-blind, placebo-controlled, three-arm study of the anti-CD4 monoclonal antibody TNX-355 with optimized background therapy in treatment-experienced subjects infected with HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 10, 2004. NLM Identifier: NCT00089700. Available at: http://www.clinicaltrials.gov/ct2/show/NCT00089700. Last accessed on November 3, 2017.
  8. Bruno CJ, Jacobson JM. Ibalizumab: an anti-CD4 monoclonal antibody for the treatment of HIV-1 infection. J Antimicrob Chemother. 2010 Sep;65(9):1839-41. Available at: http://jac.oxfordjournals.org/content/65/9/1839.long. Last accessed on November 3, 2017.
  9. 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 November 3, 2017.
  10. 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 November 3, 2017.
  11. 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 November 3, 2017.
  12. 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 November 3, 2017.
  13. TaiMed Biologics Inc. 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. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 8, 2016. NLM Identifier: NCT02707861. Available at: https://clinicaltrials.gov/ct2/show/NCT02707861. Last accessed on November 3, 2017.
  14. 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 November 3, 2017.
  15. 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 November 3, 2017.
  16. Lin HH, Lee SS, Wang NC, et al. Intramuscular ibalizumab: pharmacokinetics, safety, and efficacy vs IV administration. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 13-16, 2017; Seattle, Washington. Poster 438. Available at: http://www.croiconference.org/sites/default/files/posters-2017/438_Lewis.pdf. Last accessed on November 3, 2017.
  17. 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: Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2011; Chicago, IL; Abstract H2-794b. Available at: http://www.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 November 3, 2017.
  18. Lalezari, J. Primary efficacy endpoint and safety results of ibalizumab in a phase 3 study of heavily treatment-experienced patients with multi-drug resistant HIV-1 infection. IDWeek; October 26-30, 2016; New Orleans, LA. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2016. Available at: http://www.natap.org/2016/IDSA/IDSA_06.htm. Last accessed on November 3, 2017.
  19. Lewis S, Fessel J, Emu B, et al. Long-acting ibalizumab in patients with multi-drug resistant HIV-1: a 24-week study. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 13-16, 2017; Seattle, Washington. Poster 449LB. Available at: http://www.croiconference.org/sites/default/files/posters-2017/449LB_Emu.pdf. Last accessed on November 3, 2017.
 

Last Reviewed: November 3, 2017