Drugs

Rilpivirine LA (HIV prevention)

Rilpivirine LA (HIV prevention)

Other Names: Edurant long-acting injection, G1003 LA, RPV LA, TMC278 LA, rilpivirine long acting, rilpivirine nanosuspension Drug Class: Non-nucleoside Reverse Transcriptase Inhibitors Molecular Formula: C22 H18 N6 Registry Number: 500287-72-9 (CAS) Chemical Name: 4-((4-((4-((1E)-2-cyanoethenyl)-2,6-dimethylphenyl)amino)-2-pyrimidinyl)amino)benzonitrile Chemical Class: Diarylpyrimidines Organization: Janssen R&D Ireland; PATH Phase of Development: The study of rilpivirine LA for HIV pre-exposure prophylaxis has been discontinued. (Rilpivirine LA is currently being studied for HIV treatment in Phase III trials.)

(Compound details obtained from ChemIDplus Advanced,1 Retrovirology article,2 Janssen R&D Ireland press release,3 and ClinicalTrials.gov4,5)

NOTE: The development of rilpivirine LA for preventing sexually acquired HIV infection has been discontinued.

NOTE: The development of rilpivirine LA for preventing sexually acquired HIV infection has been discontinued.

The study of rilpivirine LA as a non-nucleoside reverse transcriptase inhibitor medicine for preventing HIV infection appears to be discontinued. In July 2017, during presentations given at the 9th International AIDS Society (IAS) Conference on HIV Science, study investigators announced that the development of rilpivirine LA for HIV prevention has been stopped.5,6

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 rilpivirine LA?

What is rilpivirine LA?

Rilpivirine LA is an investigational drug that is being studied for both the treatment and prevention of HIV infection.3,7

Rilpivirine LA belongs to a class (group) of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).2 NNRTIs attach to and block an HIV enzyme called reverse transcriptase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking reverse transcriptase, NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body.

FDA has already approved a tablet form of rilpivirine (brand name: Edurant) for the treatment of HIV.8 Rilpivirine LA is a new form of rilpivirine that is long-lasting and given as a shot. As a potential HIV treatment, this injectable type of rilpivirine could be taken less often than the tablet form of rilpivirine and make it easier for patients to stay on their HIV medicine regimens.7

Rilpivirine LA is also being studied for use as HIV pre-exposure prophylaxis (PrEP). PrEP can help prevent HIV infection when given to people who don’t have the virus.3,9 To learn more about PrEP, see the AIDSinfo fact sheet Pre-Exposure Prophylaxis (PrEP).

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.10

  • 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.10
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.10

Some clinical trials are categorized as "a" or "b" such as "Phase Ia" or "Phase II." 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 rilpivirine LA?

In what phase of testing is rilpivirine LA?

Rilpivirine LA has been studied in a Phase II clinical trial as HIV PrEP.9

What are some studies on rilpivirine LA?

What are some studies on rilpivirine LA?

Rilpivirine LA HIV PrEP studies

Study Names: MWRI-01; NCT01656018
Sponsor: Janssen Research & Development, LLC
Phase: I
Status: This study has been completed.
Location: United States
Participants: Participants were adult men and women who did not have HIV.
Purpose: The purpose of this study was to evaluate the safety, acceptability, and drug properties of rilpivirine LA.11

Study Names: HPTN 076; NCT02165202
Sponsor: PATH
Phase: II
Status: This study has been completed.
Location: South Africa, United States, and Zimbabwe
Participants: The participants were sexually active women who did not have HIV and had a low risk of being infected with the virus.
Purpose: The purpose of this study was to evaluate the safety and acceptability of rilpivirine LA when used as PrEP. In this study, rilpivirine LA was compared to placebo. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)9

For more details on this study, see the Health Professional version.

Another Phase I study that evaluated the safety and drug properties of rilpivirine LA as PrEP has also been completed (NCT01275443).12

What side effects might rilpivirine LA cause?

What side effects might rilpivirine LA cause?

One goal of HIV research is to identify new drugs that have fewer side effects. In the Phase II study (NCT02165202) discussed above, researchers reported no major differences in side effects between the rilpivirine LA and placebo groups. Some participants in both groups had temporary liver problems that were moderate or severe. Three participants in the rilpivirine LA group experienced severe reactions at the injection site. Eight percent of participants in the rilpivirine LA group and 5% of participants in the placebo group dropped out of the study because of a side effect.9,13

If testing of rilpivirine LA resumes, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying rilpivirine LA?

Where can I get more information about clinical trials studying rilpivirine LA?

More information about rilpivirine LA-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.10

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/500287-72-9. Last accessed on May 30, 2018.
  2. Johnson BC, Pauly GT, Rai G, et al. A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants. Retrovirology. 2012 Dec 5;9:99. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3549755/. Last accessed on May 30, 2018.
  3. Johnson & Johnson: Press release, dated September 25, 2013. Janssen R&D Ireland announces agreement with PATH for early development of rilpivirine in long-acting formulation for potential prophylactic intervention. Available at: https://www.jnj.com/media-center/press-releases/janssen-r-d-ireland-announces-agreement-with-path-for-early-development-of-rilpivirine-in-long-acting-formulation-for-potential-prophylactic-intervention. Last accessed on May 30, 2018. [Archived at WebCite]
  4. 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. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02951052. Last accessed on May 30, 2018.
  5. McGowan I. An open-label multiple dose phase 1 assessment of long-acting rilpivirine. Abstract presented at: International AIDS Society (IAS) Conference on HIV Science (IAS 2017), July 23-26, 2017; Paris, France. Abstract TUAC0103. Available at: http://programme.ias2017.org/PAGMaterial/PPT/1306_94/IAS%202017_MWRI-01_MD_Final.ppt. Last accessed on May 30, 2018.
  6. Tolley EE, Li S, Atujuna M. Acceptability of rilpivirine LA (RPV LA): long-acting injectable pre-exposure prophylaxis (PrEP) in HPTN 076. Poster presented at: International AIDS Society(IAS) Conference on HIV Science (IAS 2017), July 23-26, 2017; Paris, France. Poster MOLBPEC32. Available at: http://programme.ias2017.org/PAGMaterial/eposters/4678.pdf. Last accessed on May 30, 2018. [Archived at WebCite]
  7. Crauwels H. Nanoformulations – an update from Janssen. Slides presented at: International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy; May 26-28, 2015; Washington DC, USA. Available at: http://regist2.virology-education.com/2015/16HIVHEP/09_Crauwels.pdf. Last accessed on May 30, 2018. [Archived at WebCite]
  8. Janssen Products, LP. Edurant: full prescribing information, March 2017. DailyMed. Available at: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=03880372-2c68-45c6-a53a-f420c49541d6. Last accessed on May 30, 2018.
  9. PATH. HPTN 076 - Phase II safety and acceptability of an investigational injectable product, TMC278 LA, for pre-exposure prophylaxis (PrEP). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 21, 2014. NLM Identifier: NCT02165202. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02165202. Last accessed on May 30, 2018.
  10. 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 May 30, 2018.
  11. Janssen Research & Development, LLC. Phase 1 open label safety, acceptability, pharmacokinetic and ex vivo pharmacodynamic study of TMC278 long acting (LA) administered intramuscularly to HIV-1 seronegative individuals. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 31, 2012. NLM Identifier: NCT01656018. Available at: https://clinicaltrials.gov/ct2/show/NCT01656018. Last accessed on May 30, 2018.
  12. St Stephens Aids Trust. A pharmacokinetic evaluation of the exposure and distribution of TMC278LA for use as pre-exposure prophylaxis, in plasma and genital tract / rectal compartments, following a single intramuscular dose at different doses in HIV-negative healthy volunteers. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on January 11, 2011. NLM Identifier: NCT01275443. Available at: https://clinicaltrials.gov/ct2/show/NCT01275443. Last accessed on May 30, 2018.
  13. Bekker L-G, Li S, Tolley E, et al. HPTN 076: TMC278 LA safe, tolerable and acceptable for HIV pre-exposure prophylaxis. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 13-16, 2017; Seattle, WA. Poster 421LB. Available at: http://www.croiconference.org/sites/default/files/posters-2017/421LB_Bekker.pdf. Last accessed on May 30, 2018.

Last Reviewed: May 30, 2018