Drugs

ABX464

ABX464

Drug Class: Rev Inhibitor Molecular Formula: C16 H10 Cl F3 N2 Registry Number: 1258453-75-6 (CAS) Chemical Name: 8-chloro-N-[4-(trifluoromethoxy)phenyl]quinolin-2-amine Organization: Abivax S.A. Phase of Development: IIa

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and ClinicalTrials.gov3)

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 ABX464?

What is ABX464?

ABX464 is an investigational drug that is being studied for the treatment of HIV infection.

ABX464 belongs to a class (group) of HIV drugs called Rev inhibitors.2 Rev is an HIV protein that helps to transport HIV’s genetic information within an infected immune cell. The Rev protein is essential for HIV to replicate and produce new virus.4 By interfering with the activity of the Rev protein, Rev inhibitors prevent HIV from multiplying and may reduce the amount of HIV in the body.5

Researchers suggest that ABX464 may also help a person’s own immune system to recognize and reduce or eliminate latent HIV reservoirs in the body.5,6 A latent HIV reservoir is a group of immune cells in the body that are infected with HIV but are not actively producing new HIV. Because current HIV medicines do not work against HIV that's hidden in latent reservoirs, these reservoirs are one of the main obstacles to curing HIV infection.

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.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.
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  

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 ABX464?

In what phase of testing is ABX464?

ABX464 has been studied in Phase IIa clinical trials.3,8

What are some studies on ABX464?

What are some studies on ABX464?

Study Names: ABX464-003; NCT02452242 
Sponsor: Abivax S.A.  
Phase: IIa 
Status: This study has been completed. 
Location: Mauritius and Thailand  
Participants: 

  • Participants were adults with HIV-1 or HIV-2 who had never taken HIV medicines before entering the study. 
  • Participants had viral load levels (the amount of HIV in a blood sample) between 5,000 and 500,000 copies/mL. 
  • Participants had CD4 counts of at least 350 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 evaluate the safety, effectiveness, and pharmacokinetics of ABX464. (Pharmacokinetics is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body.)8,9

Study Names: ABX464-004; NCT02735863 
Sponsor: Abivax S.A.   
Phase: IIa
Status: This study has been completed.
Location: Belgium, France, and Spain 
Participants:
  • Participants were adults with HIV who had been taking darunavir plus either ritonavir or cobicistat for at least 8 weeks before the start of the study. 
  • Participants had the following viral load levels at the specified time points: 
    • 100,000 copies/mL or less from the time their HIV was diagnosed (except during the earliest stage of infection).
    • 50 copies/mL or less during the 6 months before the start of the study. 
  • Participants had the following CD4 counts at the specified time points: 
    • 250 cells/mm3 or greater from the time their HIV was diagnosed. 
    • 600 cells/mm3 or greater at the start of the study. 
Purpose: The purpose of this study was to evaluate the safety of two different doses (50 mg and 150 mg) of ABX464. The study also examined the effect of ABX464 on latent HIV reservoirs and on viral load levels during a treatment interruption. (A treatment interruption is a planned break from HIV medicines to evaluate how well an investigational drug can maintain control of a participant’s viral load during a clinical trial.)3,6  

Study Names: ABX464-005; NCT02990325
Sponsor: Abivax S.A.
Phase: I/II
Status: This study is currently recruiting participants.
Location: Spain 
Participants:
  • Participants are adult males with HIV and without HIV.
  • Participants with HIV:
Purpose: The purpose of this study is to evaluate the safety of ABX464. The study will also examine the pharmacokinetics of ABX464 and the drug’s effects on the body.10 

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

What side effects might ABX464 cause?

What side effects might ABX464 cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of ABX464 listed above.

ABX464-003 (NCT02452242):
In this study, the majority of participants receiving ABX464 reported a side effect, but none of the side effects were serious, and no one quit the study because of a side effect. The most common side effects related to ABX464 were headache, nausea, and vomiting. Other side effects experienced by participants on ABX464 included upper abdominal pain and skin rash.

ABX464-004 (NCT02735863):
In this study, there were no drug-related side effects among the participants receiving the 50-mg dose of ABX464. However, 8 of the participants receiving the 150-mg dose of ABX464 had a drug-related side effect, most often moderate abdominal pain and headache. Among those receiving the 150-mg dose of ABX464, 1 participant had severe fatigue related to ABX464 treatment, and another participant quit the study early because of ABX464-related moderate abdominal pain and mild epigastric pain.3, 6

Because ABX464 is still being studied, information on possible side effects of the drug is not complete. As testing of ABX464 continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying ABX464?

Where can I get more information about clinical trials studying ABX464?

More information about ABX464-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.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.

References

References

  1. United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem.nlm.nih.gov/chemidplus/rn/1258453-75-6. Last accessed on November 1, 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 1, 2017.
  3. Abivax S.A. A Multi-center, randomized, double-blind, placebo-controlled Phase IIa trial to compare the safety of ABX464 given at a fixed dose to placebo in fully controlled HIV infected patients treated with boosted protease inhibitor treatment (darunavir/ritonavir or darunavir/cobicistat). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 8, 2016. NLM Identifier: NCT02735863. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02735863. Last accessed on November 1, 2017.
  4. Hope TJ, Trono D. Structure, Expression, and Regulation of the HIV Genome. In: Coffey S and Volberding P, eds. HIV InSite Knowledge Base. University of California San Francisco; 2000. Available at: http://hivinsite.ucsf.edu/InSite?page=kb-02-01-02#S2.2.2X. Last accessed on November 1, 2017.
  5. Abivax website. ABX464/HIV. Available at: http://www.abivax.com/en/development-products/abx464.html. Last accessed on November 1, 2017.
  6. Paredes R, Vandekerckhove L, Clotet B, et al. ABX464 decreases total HIV DNA in PBMCs when administered during 28 Days to HIV-infected virologically Suppressed Patients. Poster presented at: International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2016; Paris, France. Poster TULBPEB22. Available at: http://programme.ias2017.org//PAGMaterial/eposters/5650.pdf. Last accessed on November 1, 2017.
  7. 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 1, 2017.
  8. Steens JM, Scherrer D, Gineste P, et al. Safety, pharmacokinetics, and antiviral activity of a novel HIV antiviral, ABX464, in treatment-naive HIV-infected subjects in a Phase 2 randomized, controlled study. Antimicrob Agents Chemother. 2017 Jul; 61(7): e00545-17. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487684/. Last accessed on November 1, 2017.
  9. Abivax S.A. A Phase 2, dose escalation, schedule comparison study to evaluate the safety, pharmacokinetics, and viral kinetics of ABX464 in untreated patients with HIV infection in mauritius. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 10, 2015. NLM Identifier: NCT02452242. Available at: https://clinicaltrials.gov/ct2/show/NCT02452242. Last accessed on November 1, 2017.
  10. Abivax S.A. An open-label study of the safety, pharmacokinetics, and pharmacodynamics of ABX464 in HIV-1 seronegative and seropositive adults. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on December 7, 2016. NLM Identifier: NCT02990325. Available at: https://clinicaltrials.gov/ct2/show/NCT02990325. Last accessed on November 1, 2017.

Last Reviewed: November 1, 2017