Drugs

Cabotegravir

Cabotegravir

Other Names: 744 LA, CAB, 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 III development for both HIV treatment and HIV prevention. Patients who do not qualify for or are unable to participate in the Phase III 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).

(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 HIV/AIDS (Auckland, N.Z.) article,3  ViiV Healthcare website,4 and ClinicalTrials.gov5)

What is cabotegravir?

What is cabotegravir?

Cabotegravir (CAB) is an investigational drug that is being studied to treat and prevent HIV infection.6 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).7,8

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: (1) LAI116482 (LATTE); NCT01641809 and (2) POLAR; NCT03639311
Phase: IIb
Status: The LATTE study is ongoing, but not recruiting participants. The POLAR trial has not started recruiting participants.
Locations: United States and Canada (LATTE study only)
Purpose: The purpose of the LATTE study is to find a safe and effective dose of oral cabotegravir to give with the HIV oral medicine rilpivirine (brand name: Edurant) as a two-drug treatment regimen for HIV maintenance therapy.7,9,10 The POLAR study is a follow-on study in LATTE participants that will evaluate the safety and effectiveness of cabotegravir LA used with a long-acting injectable form of rilpivirine (known as rilpivirine LA). Rilpivirine LA is also an investigational drug.11

Study Names: LATTE-2; NCT02120352
Phase: IIb
Status: This study is ongoing, but not recruiting participants.
Locations: United States, Canada, France, Germany, Spain
Purpose: The purpose of this study is to evaluate the safety and effectiveness of two different dosing regimens of cabotegravir LA plus rilpivirine LA for HIV maintenance therapy. The cabotegravir LA plus rilpivirine LA regimen will be compared to a regimen of oral cabotegravir plus other oral HIV medicines. Results from this study will be used to select a regimen of cabotegravir LA plus rilpivirine LA to evaluate in Phase III studies.8,12

Study Names: ATLAS; NCT02951052
Phase: III
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.13

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

  • FLAIR (NCT02938520): This Phase III study will evaluate whether cabotegravir LA plus rilpivirine LA is safe and effective at maintaining viral suppression after a switch from an oral HIV regimen. This study is ongoing, but not recruiting participants.14
  • ATLAS-2M (NCT03299049): This Phase III study will evaluate the safety and effectiveness of cabotegravir LA plus rilpivirine LA given every 8 weeks or every 4 weeks in participants with viral suppression. This study is ongoing, but not recruiting participants.15
  • ACTG A5359 (NCT03635788): This Phase III study will compare the safety and effectiveness of cabotegravir LA plus rilpivirine LA to a standard oral HIV regimen in participants with a history of poor adherence to antiretroviral therapy and poorly controlled HIV. This study has not started recruiting participants.16

Cabotegravir for HIV Prevention

Study Names: ECLAIR; NCT02076178
Phase: IIa
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.17,18

Study Names: HPTN 077; NCT02178800
Phase: IIa
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.19

Additional studies will be evaluating cabotegravir LA for HIV prevention:
  • HPTN 083 (NCT02720094): This Phase IIb/III study will compare the safety and effectiveness of cabotegravir LA for PrEP to tenofovir disoproxil fumarate/emtricitabine (brand name: Truvada), the FDA-approved HIV drug for PrEP. Participants are cis men and transgender women without HIV who have sex with men and are at high risk of getting HIV during sex. This study is currently recruiting participants.20
  • HPTN 084 (NCT03164564): This Phase III study will compare the safety and effectiveness of cabotegravir LA for PrEP to Truvada. Study participants will be women without HIV who are at risk of getting HIV during sex. HPTN 084 is currently recruiting participants.21

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.

LATTE (NCT01641809):

Study researchers reported that oral cabotegravir was generally well tolerated.7,10,22,23 Cabotegravir-related side effects included insomnia, depression, nausea, fatigue, and headache.

LATTE-2 (NCT02120352):

The most common side effect among participants receiving cabotegravir LA plus rilpivirine LA was pain at the site of the injections. Most injection site reactions were mild to moderate in severity and went away on their own. However, two participants dropped out of the study because of injection site reactions. Other common side effects during the study were cold symptoms, diarrhea, and headache. Cabotegravir may have caused liver damage in two participants receiving oral cabotegravir. However, when the participants stopped taking cabotegravir, their liver tests returned to normal.24

Overall, LATTE-2 participants receiving cabotegravir LA reported being satisfied with the treatment and were willing to continue with the injections after Week 32 of the study. Participants also preferred cabotegravir LA injections to oral cabotegravir in terms of convenience, flexibility, and ease of use.25

ECLAIR (NCT02076178):

The most common injection site reactions related to cabotegravir LA were pain, swelling, and itching.17,18 Seven participants dropped out of the study while receiving oral cabotegravir. One participant left the study because of excessive tiredness, three left because of signs of muscle or organ injury, and three left because of low levels of infection-fighting cells called neutrophils.26

HPTN 077 (NCT02178800):

Injection site reactions occurred frequently in participants receiving cabotegravir LA but were generally mild. Injection site pain and headache were more common among participants receiving cabotegravir than among those receiving placebo injections.19,27

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 January 4, 2019.
  2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. https://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Accessed January 4, 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/our-medicines/medicines-in-development.aspx. Accessed January 4, 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 January 4, 2019.
  6. 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 January 4, 2019.
  7. 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 January 4, 2019.
  8. 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 January 4, 2019.
  9. Margolis D, Bhatti L, Smith G, et al. Once-daily oral GSK1265744 (GSK744) as part of combination therapy in antiretroviral naïve adults: 24-week safety and efficacy results from the LATTE Study (LAI116482). Abstract presented at: 14th European AIDS Conference; October 16-19, 2013; Brussels, Belgium. Abstract PS7/1. http://www.professionalabstracts.com/eacs2013/planner/index.php?go=abstract&action=abstract_iplanner&print=0&lprID=148&highlight=GSK1265744&PSID=IVXPCJJQVIXZCSVVMQWX. Accessed January 4, 2019.
  10. Margolis DA, Brinson CC, Smith GHR, et al. Cabotegravir and rilpivirine as two-drug oral maintenance therapy: LATTE Week 96 results. Poster presented at: 22nd Conference on Retroviruses and Opportunistic Infections (CROI); February 23-26, 2015; Seattle, WA. Poster 554LB. http://www.croiconference.org/sites/default/files/posters-2015/554LB.pdf. Accessed January 4, 2019.
  11. ViiV Healthcare. A Phase IIb, multicenter, open-label, rollover study evaluating the efficacy, safety and tolerability of long-acting cabotegravir plus long-acting rilpivirine administered every two months in HIV-1 infected adults who are virologically suppressed and participated in study LAI116482. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 10, 2018. NLM Identifier: NCT03639311. https://www.clinicaltrials.gov/ct2/show/NCT03639311. Accessed January 4, 2019.
  12. Margolis DA, Gonzalez-Garcia J, Stellbrink H-J, et al. Cabotegravir + rilpivirine as long-acting maintenance therapy: LATTE-2 week 32 results. 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Levin: Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2016. http://www.natap.org/2016/CROI/croi_06.htm. Accessed January 4, 2019.
  13. 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 January 4, 2019.
  14. 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 January 4, 2019.
  15. 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 January 4, 2019.
  16. 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 January 4, 2019.
  17. 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 January 4, 2019.
  18. 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 January 4, 2019.
  19. 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 January 4, 2019.
  20. 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 January 4, 2019.
  21. 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 January 4, 2019.
  22. Margolis D, Brinson C, Eron J, et al. 744 and rilpivirine as two drug oral maintenance therapy: LAI116482 (LATTE) week 48 results. 21st Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2014; Boston, MA. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2014. http://www.natap.org/2014/CROI/croi_27.htm. Accessed January 4, 2019.
  23. Margolis DA, Brinson C, Smith GH, et al. Long-term safety and efficacy of CAB and RPV as 2-drug oral maintenance therapy. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 13-16, 2017; Seattle, WA. Poster 442. http://www.croiconference.org/sites/default/files/posters-2017/442_Margolis.pdf. Accessed January 4, 2019.
  24. Margolis DA, Gonzalez-Garcia J, Stellbrink H-J, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. The Lancet. 2017;390(10101):1499-1510.
  25. Murray M, Dorey D, Griffith S, Mrus J, Spreen W, Margolis D. Satisfaction, tolerability, and acceptability of cabotegravir (CAB) + rilpivirine (RPV) long-acting therapy: LATTE-2 results. Poster presented at: 21st International AIDS Conference; July 18-22, 2016; Durban, South Africa. Poster THPEB052. http://programme.aids2016.org/PAGMaterial/eposters/0_5385.pdf. Accessed January 4, 2019.
  26. Markowitz M, Frank I, Grant R, et al. ECLAIR: Phase 2A safety and PK study of cabotegravir LA in HIV-uninfected men. Abstract presented at: 23rd Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA. Abstract 106. http://www.croiconference.org/sessions/%C3%A9clair-phase-2a-safety-and-pk-study-cabotegravir-la-hiv-uninfected-men. Accessed January 4, 2019.
  27. 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 January 4, 2019.

Last Reviewed: January 4, 2019