Drugs

Cabotegravir

Cabotegravir

Other Names: 744 LA, CAB, CAB LA, GSK-1265744, GSK1265744, GSK744, GSK744 LA, GSK744 LAP, S-265744, S/GSK1265744, cabotegravir LA, cabotegravir sodium Drug Class: Integrase Inhibitors Molecular Formula: C19 H17 F2 N3 O5 Registry Number: 1051375-10-0 (CAS) Chemical Name: (3S,11aR)-N-((2,4-difluorophenyl)methyl)-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo(3,2-a)pyrido(1,2-d)pyrazine-8-carboxamide Chemical Class: Carbamoyl pyridone Organization: ViiV Healthcare Phase of Development:

Cabotegravir is in Phase 3 development for both HIV treatment and HIV prevention. Patients who do not qualify for or are unable to participate in the Phase 3 clinical studies of cabotegravir for HIV treatment may be able to obtain the drug through an expanded access (also called compassionate use) treatment program. For details on the program, go to ClinicalTrials.gov (NCT03462810).

An application for marketing approval of a long-acting two-drug regimen consisting of cabotegravir and rilpivirine for HIV treatment was submitted to the U.S. Food and Drug Administration (FDA) in April 2019. The submission to FDA also included an application for approval of an oral formulation of cabotegravir.

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 HIV/AIDS (Auckland, N.Z.) article,3 ViiV Healthcare website,4 ClinicalTrials.gov,5 and ViiV Healthcare press release6)

What is cabotegravir?

What is cabotegravir?

Cabotegravir (CAB) is an investigational drug that is being studied to treat and prevent HIV infection.7 Cabotegravir is being studied in two forms: as a tablet taken by mouth (called oral cabotegravir or oral CAB) and as a long-acting (LA) injectable given as a shot (called cabotegravir LA or CAB LA).8,9

Cabotegravir belongs to a group of HIV drugs called integrase inhibitors.2 Integrase inhibitors block an HIV enzyme called integrase. By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body.

To learn about how investigational drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

Which clinical trials are studying cabotegravir?

Which clinical trials are studying cabotegravir?

Cabotegravir for HIV Treatment

Study Names: ATLAS; NCT02951052
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Argentina, Australia, Canada, France, Germany, Italy, Mexico, Republic of Korea, Russian Federation, South Africa, Spain, Sweden
Purpose: The purpose of this study is to evaluate the safety and effectiveness of switching people with viral suppression on an oral HIV treatment regimen to a cabotegravir LA plus rilpivirine LA regimen.10

Study Names: FLAIR; NCT02938520
Phase: 3
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Canada, France, Germany, Italy, Japan, Netherlands, Russian Federation, South Africa, Spain, United Kingdom
Purpose: The purpose of this study is to evaluate the safety and effectiveness of a two-drug regimen of cabotegravir LA plus rilpivirine LA in maintaining virologic suppression in adults who switched from a suppressive oral HIV regimen to the two-drug injectable regimen. The study participants will be adults with HIV who upon entering the study have never taken HIV medicines.11

Study Names: LATITUDE; ACTG A5359; NCT03635788
Phase: 3
Status: This study is currently recruiting participants.
Location: United States
Purpose: The purpose of this study is to compare the safety and effectiveness of cabotegravir LA plus rilpivirine LA versus all-oral standard of care ART in adults with a history of poor adherence to ART and poorly controlled HIV.12

Study Names: ATLAS-2M; NCT03299049
Phase: 3b
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Argentina, Australia, Canada, France, Germany, Italy, Korea, Mexico, Russian Federation, South Africa, Spain, Sweden
Study Purpose: The purpose of this study is to evaluate the safety and effectiveness of cabotegravir LA plus rilpivirine LA in adults with HIV who are virologically suppressed.13

Other ongoing or planned studies on cabotegravir LA for HIV treatment include the following:

  • MOCHA (NCT03497676): A Phase 1/2 study that will evaluate the safety, acceptability, tolerability, and pharmacokinetics of oral cabotegravir, cabotegravir LA, and rilpivirine LA in virologically suppressed children and adolescents with HIV. This study is currently recruiting participants.14
  • ACTG A5357 (NCT03739996): A Phase 2 study that will evaluate whether cabotegravir LA plus the broadly neutralizing antibody (bNAb) VRC01LS can maintain viral suppression in adults with HIV. See the ClinicalTrials.gov record for the status of this study.15


Cabotegravir for HIV Prevention

Study Names: ECLAIR; NCT02076178
Phase: 2a
Status: This study has been completed.
Location: United States
Purpose: The purpose of this study was to evaluate the safety, tolerability, and acceptability of cabotegravir LA for pre-exposure prophylaxis (PrEP). Participants received both oral cabotegravir and cabotegravir LA injections over the course of the study, and cabotegravir was compared to a placebo.16,17

Study Names: HPTN 077; NCT02178800
Phase: 2a
Status: This study has been completed.
Locations: United States, Brazil, Malawi, South Africa
Purpose: The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of cabotegravir LA in participants without HIV. In this study, cabotegravir LA was compared to a placebo. Over the course of the study, participants received either oral cabotegravir and cabotegravir LA or oral placebo and injectable placebo.18

Study Names: HPTN 083; NCT02720094
Phase: 2b/3
Status: This study is currently recruiting participants.
Locations: United States, Argentia, Brazil, Peru, South Africa, Thailand, Vietnam
Purpose: The purpose of this study is to compare the safety and effectiveness of cabotegravir LA to oral tenofovir disoproxil fumarate/emtricitabine for PrEP.19

Study Names: HPTN 084; NCT03164564
Phase: 3
Status: This study is currently recruiting participants.
Locations: Botswana, Kenya, Malawi, South Africa, Swaziland, Uganda, Zimbabwe
Purpose: The purpose of this study is to compare the safety and effectiveness of cabotegravir LA to oral tenofovir disoproxil fumarate/emtricitabine for PrEP.20

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

What side effects might cabotegravir cause?

What side effects might cabotegravir 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 cabotegravir listed above.

ATLAS (NCT02951052):

The most common drug-related side effects among participants receiving cabotegravir LA plus rilpivirine LA were fatigue, fever, headache, and nausea. Most drug-related side effects reported by participants receiving cabotegravir LA plus rilpivirine LA were mild or moderate and none were serious. Only 3% of participants receiving cabotegravir LA plus rilpivirine LA withdrew from the study because of a side effect.21

Injection site reactions were commonly reported by participants in the study, but most were mild or moderate in intensity and resolved within 7 days. Four participants withdrew from the study because of injection site reactions. The most common injection site reactions among participants receiving cabotegravir LA plus rilpivirine LA was injection-site pain.21,22

FLAIR (NCT02938520):

With the exception of injection site reactions, headache and fever were the most common drug-related side effects reported by participants in the study. Most of the drug-related side effects reported by participants receiving cabotegravir LA plus rilpivirine LA were mild or moderate in intensity. Only 3% of participants receiving cabotegravir LA plus rilpivirine LA withdrew from the study because of a side effect. Only one participant receiving cabotegravir LA plus rilpivirine LA reported a serious, drug-related side effect—arthritis of the right knee.23

Injection site reactions were common. Injection-site pain was the most frequently reported injection site reaction, and led to the withdrawal of two participants from the study. Two additional participants withdrew from the study because of injection intolerability. Most injection site reactions decreased over time, were mild or moderate in intensity, and lasted for about three days.23,24

ECLAIR (NCT02076178):

Overall, the frequency of reported side effects was similar for participants in the cabotegravir and placebo groups. However, moderate to serious side effects were more frequently reported by participants receiving cabotegravir (80% of participants) than by those taking placebo (48% of participants), mainly because injection site pain was reported more often by participants taking cabotegravir.25

During the oral therapy part of the study, treatment-related side effects were mostly mild to moderate and occurred in 36% of participants taking oral cabotegravir and in 14% of participants taking the oral placebo. No serious side effects were reported among participants taking oral cabotegravir.25

Ninety three percent of participants receiving cabotegravir LA versus 57% of participants receiving the injectable placebo reported an injection site reaction. The majority of injection site reactions in participants taking cabotegravir LA were mild (80%) to moderate (56%). Nineteen percent of participants taking cabotegravir LA experienced a serious injection site reaction. Other injection site reactions reported by participants taking cabotegravir LA included mild itchiness, nodules/bumps, warmth to the touch, bruising, and hardened tissue.25

HPTN 077 (NCT02178800):

Ten participants discontinued cabotegravir because of drug-related side effects, including gastrointestinal problems, rash, and neurologic issues. Serious side effects reported by participants taking cabotegravir included vertigo and weakness.26

During the injection phase of the study, moderate or serious side effects occurred in 91% of participants receiving cabotegravir LA versus 88% of participants receiving the injectable placebo. Injection site reactions were the only moderate or serious side effects that were significantly more common in participants receiving cabotegravir than in those receiving placebo. Only one participant discontinued cabotegravir due to an injection site reaction. Two participants taking cabotegravir had a serious injection site reaction, although neither participant stopped taking cabotegravir.26

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

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

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

More information about cabotegravir-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.

Some clinical trials may be looking for volunteer participants. 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: cabotegravir. https://chem.nlm.nih.gov/chemidplus/rn/1051375-10-0. Accessed July 30, 2019
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed July 30, 2019
  3. Whitfield T, Torkington A, van Halsema C. Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date. HIVAIDS Auckl NZ. 2016;8:157-164.
  4. ViiV Healthcare website. Medicines in development. https://www.viivhealthcare.com/en-gb/our-medicines/medicines-in-development/. Accessed July 30, 2019
  5. ViiV Healthcare. GSK1265744 (Cabotegravir, CAB) for named patient/compassionate use in HIV. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 5, 2018. NLM Identifier: NCT03462810. https://www.clinicaltrials.gov/ct2/show/NCT03462810. Accessed July 30, 2019
  6. ViiV Healthcare: Press Release, dated April 29, 2019. ViiV Healthcare submits New Drug Application to US FDA for the first monthly, injectable, two-drug regimen of cabotegravir and rilpivirine for treatment of HIV. https://www.viivhealthcare.com/en-gb/media/press-releases/2019/april/viiv-healthcare-submits-new-drug-application-to-us-fda-for-the-first-monthly-injectable-two-drug-regimen-of-cabotegravir-and-rilpivirine-for-treatment-of-hiv/. Accessed July 30, 2019
  7. Ford S, Margolis D, Chen S, Gould E, Spreen W. Plasma and tissue GSK1265744 pharmacokinetics following long-acting parenteral administration in healthy male and female subjects. Abstract presented at: 14th International Workshop on Clinical Pharmacology of HIV Therapy; April 22-24, 2013; Amsterdam, The Netherlands. Abstract O_02. http://regist2.virology-education.com/abstractbook/2013_3.pdf. Accessed July 30, 2019
  8. ViiV Healthcare. A Phase IIb, dose ranging study of oral GSK1265744 in combination with nucleoside reverse transcriptase inhibitors for induction of human immunodeficiency virus -1 (HIV-1) virologic suppression followed by an evaluation of maintenance of virologic suppression when oral GSK1265744 is combined with oral rilpivirine in HIV-1 infected, antiretroviral therapy naive adult subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 28, 2012. NLM Identifier: NCT01641809. https://clinicaltrials.gov/ct2/show/NCT01641809. Accessed July 30, 2019
  9. ViiV Healthcare. A Phase IIb study evaluating a long-acting intramuscular regimen of GSK1265744 plus TMC278 for the maintenance of virologic suppression following an induction of virologic suppression on an oral regimen of GSK1265744 plus abacavir/lamivudine in HIV-1 infected, antiretroviral therapy-naive adult subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 17, 2014. NLM Identifier: NCT02120352. https://clinicaltrials.gov/ct2/show/NCT02120352. Accessed July 30, 2019
  10. ViiV Healthcare. A Phase III, randomized, multicenter, parallel-group, non-inferiority, open-label study evaluating the efficacy, safety, and tolerability of switching to long-acting cabotegravir plus long-acting rilpivirine from current INI- NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 15, 2016. NLM Identifier: NCT02951052. https://clinicaltrials.gov/ct2/show/NCT02951052. Accessed July 30, 2019
  11. ViiV Healthcare. A Phase III, randomized, multicenter, parallel-group, open-label study evaluating the efficacy, safety, and tolerability of long-acting intramuscular cabotegravir and rilpivirine for maintenance of virologic suppression following switch from an integrase inhibitor single tablet regimen in HIV-1 infected antiretroviral therapy naive adult participants. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 15, 2016. NLM Identifier: NCT02938520. https://clinicaltrials.gov/ct2/show/NCT02938520. Accessed July 30, 2019
  12. National Institute of Allergy and Infectious Diseases. A Phase III study to evaluate long-acting antiretroviral therapy in non-adherent HIV-infected individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 15, 2018. NLM Identifier: NCT03635788. https://clinicaltrials.gov/ct2/show/NCT03635788. Accessed July 30, 2019
  13. ViiV Healthcare. A Phase IIIb, randomized, multicenter, parallel-group, non-inferiority, open-label study evaluating the efficacy, safety, and tolerability of long-acting cabotegravir plus long-acting rilpivirine administered every 8 weeks or every 4 weeks in HIV-1-infected adults who are virologically suppressed. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 2, 2017. NLM Identifier: NCT03299049. https://clinicaltrials.gov/ct2/show/NCT03299049. Accessed July 30, 2019
  14. National Institute of Allergy and Infectious Diseases (NIAID). Phase I/II study of the safety, acceptability, tolerability, and pharmacokinetics of oral and long-acting injectable cabotegravir and long-acting injectable rilpivirine in virologically suppressed HIV-infected children and adolescents. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 6, 2018. NLM Identifier: NCT03497676. https://clinicaltrials.gov/ct2/show/NCT03497676. Accessed July 30, 2019
  15. National Institute of Allergy and Infectious Diseases (NIAID). A study of long-acting cabotegravir plus VRC01LS to maintain viral suppression in adults living with HIV-1. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 9, 2018. NLM Identifier: NCT03739996. https://clinicaltrials.gov/ct2/show/NCT03739996. Accessed July 30, 2019
  16. ViiV Healthcare. A Phase IIa study to evaluate the safety, tolerability and acceptability of long acting injections of the HIV integrase inhibitor, GSK1265744, in HIV uninfected men (ECLAIR). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 27, 2014. NLM Identifier: NCT02076178. https://clinicaltrials.gov/ct2/show/NCT02076178. Accessed July 30, 2019
  17. Murray M, Markowitz M, Frank I, et al. Tolerability and acceptability of cabotegravir LA injection: results from the ECLAIR study. Poster presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Poster 471. http://www.croiconference.org/sites/default/files/posters-2016/471.pdf. Accessed July 30, 2019
  18. National Institute of Allergy and Infectious Diseases (NIAID). A Phase IIa study to evaluate the safety, tolerability and pharmacokinetics of the investigational injectable HIV integrase inhibitor, GSK1265744, in HIV-uninfected men and women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on June 27, 2014. NLM Identifier: NCT02178800. https://clinicaltrials.gov/ct2/show/NCT02178800. Accessed July 30, 2019
  19. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 2b/3 double blind safety and efficacy study of injectable cabotegravir compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), for pre-exposure prophylaxis in HIV-uninfected cisgender men and transgender women who have sex with men. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 21, 2016. NLM Identifier: NCT02720094. https://clinicaltrials.gov/ct2/show/NCT02720094. Accessed July 30, 2019
  20. National Institute of Allergy and Infectious Diseases (NIAID). A Phase 3 double blind safety and efficacy study of long-acting injectable cabotegravir compared to daily oral TDF/FTC for pre-exposure prophylaxis in HIV-uninfected women. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 22, 2017. NLM Identifier: NCT03164564. https://clinicaltrials.gov/ct2/show/NCT03164564. Accessed July 30, 2019
  21. Swindells S. Long-acting cabotegravir + rilpivirine as maintenance therapy: ATLAS Week 48 results. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. http://www.croiwebcasts.org/console/player/41308?mediaType=slideVideo&&crd_fl=0&ssmsrq=1552603335674&ctms=5000&csmsrq=5060. Accessed July 30, 2019
  22. Swindells S, Andrade-Villanueva J-F, Richmond GJ, et al. Long-acting cabotegravir + rilpivirine as maintenance therapy: ATLAS Week 48 results. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Abstract 139. http://www.croiconference.org/sessions/long-acting-cabotegravir-rilpivirine-maintenance-therapy-atlas-week-48-results. Accessed July 30, 2019
  23. Orkin C. Long-acting cabotegravir + rilpivirine for HIV maintenance: FLAIR Week 48 results. Webcast presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. http://www.croiwebcasts.org/console/player/41309?mediaType=slideVideo&&crd_fl=0&ssmsrq=1552868268167&ctms=5000&csmsrq=5056. Accessed July 30, 2019
  24. Orkin C, Arastéh K, Hernández-Mora MG, et al. Long-acting cabotegravir + rilpivirine for HIV maintenance: FLAIR Week 48 results. Abstract presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7, 2019; Seattle, WA. Abstract 140. http://www.croiconference.org/sessions/long-acting-cabotegravir-rilpivirine-hiv-maintenance-flair-week-48-results. Accessed July 30, 2019
  25. Murray M, Markowitz M, Frank I, et al. Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial. HIV Clin Trials. 2018;19:1-10. doi:10.1080/15284336.2018.1511346
  26. Landovitz R, Li S, Grinsztejn B, et al. Safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in low-risk HIV-uninfected women and men HPTN 077. Slides presented at: International AIDS Society (IAS) Conference on HIV Science; July 23-26, 2017; Paris, France. http://programme.ias2017.org/PAGMaterial/PPT/2899_91/IAS2017_Landovitz_Final_072417.pptx. Accessed July 30, 2019

Last Reviewed: July 30, 2019

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