KP-1461Other Names: prodrug of KP-1212 Drug Class: Nucleoside Reverse Transcriptase Inhibitors (Viral Decay Accelerators) Molecular Formula: C16 H28 N4 O6 Registry Number: 815588-85-3 (CAS) Chemical Name: Carbamic acid, (5-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,4,5,6-tetrahydro-4-oxo-1,3,5-triazin-2-yl)-, heptyl ester Chemical Class: Azapyrimidine Nucleosides Organization: Koronis Pharmaceuticals Phase of Development: IIa
(Compound details obtained from ChemIDplus Advanced,1 NIAID Therapeutics Database,2 and AIDS Research and Human Retroviruses article3)
What is an investigational drug?
Anis one that is under study and is not approved by the U.S. (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 What is an Investigational HIV Drug? fact sheet.
What is KP-1461?
KP-1461 is an investigational drug that has been studied for the treatment of HIV.
KP-1461 belongs to a class (group) of HIV drugs calledinhibitors (NRTIs).2 Typically, NRTIs block an HIV called reverse transcriptase, which prevents HIV RNA from being converted to HIV DNA. (An enzyme is a that starts or increases the speed of a chemical reaction.) Preventing the conversion of HIV RNA to HIV DNA stops HIV from multiplying.
KP-1461, however, does not work like a typical NRTI. With KP-1461, HIV RNA is still converted to HIV DNA. But KP-1461 introduces changes in the form of the newly created HIV DNA (called mutations). These mutations harm HIV rather than help it survive. In theory, KP-1461 eventually causes so much mutated HIV to build up that thecannot continue to live and in the body. This method to stop HIV from multiplying is called viral decay acceleration. And KP-1461 is known as a viral decay accelerator.3-6
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.7
In most cases, an investigational drug must be proven effective and must show continued safety in a Phase IIIto 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 KP-1461?
KP-1461 has been studied in a Phase IIa clinical trial.2,3
What are some studies on KP-1461?
Study Names: KP-1461-201; NCT00504452
Sponsor: Koronis Pharmaceuticals
Status: This study has been completed.
Location: United States and Puerto Rico
- Participants were adults with HIV who had previously taken HIV medicines before entering the study.
- Participants had previously received (ART) that did not control their (the amount of HIV in a blood sample) and/or had to multiple classes of HIV medicines. (ART is the recommended treatment for HIV infection and involves using a combination of different (ARV) drugs to prevent HIV from multiplying. Drug resistance is when a person’s HIV mutates and becomes insensitive to a drug that was previously effective.)
- Participants were required to be off ART for at least 16 weeks before starting the study.
- Participants had viral load levels greater than 2,500 copies/mL.
- While the participants were off ART, they had stable CD4 cell counts that were above 250 cells/mm3. (A 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 look at the safety and effectiveness of KP-1461 when the drug was taken without any other HIV medicines.3,8
For more details on the study described above, see the Health Professional version.
A Phase I study (NCT00129194) has also been completed that examined the safety and drug properties of KP-1461 in participants with HIV who had previously tried 2 or more ART regimens that did not control their viral loads.9
What side effects might KP-1461 cause?
One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in one of the studies of KP-1461 listed above.
In this Phase IIa study, the majority of participants reported at least 1 side effect. Most of the reported side effects were mild to moderate in severity. Half of participants experienced at least 1 side effect that was considered possibly related to KP-1461. The most frequently reported KP-1461-related side effects were digestive system disorders and nervous system disorders. Nausea was the most common digestive system disorder. Dizziness and impaired taste were the most common nervous system disorders.3
Information on possible side effects of KP-1461 is not complete. As testing of KP-1461 continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying KP-1461?
More information about KP-1461-related research studies is available from ClinicalTrials.gov.
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.
- United States National Library of Medicine. ChemIDplus Advanced. Available at: https://chem. nlm.nih.gov/chemidplus/rn/815588-85-3. Last accessed on April 12, 2018.
- 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 April 12, 2018.
- Hicks C, Clay P, Redfield R, et al. Safety, tolerability, and efficacy of KP-1461 as monotherapy for 124 days in antiretroviral-experienced, HIV type 1-infected subjects. AIDS Res Hum Retroviruses. 2013 Feb; 29(2): 250–255. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552433/. Last accessed on April 12, 2018.
- Evans D. KP-1461: A novel anti-HIV drug in limbo? BETA. 2010 Winter-Spring; 22(2): 9-11. Available at: http://sfaf.org/hiv-info/hot-topics/beta/beta_2010_winspr_drugwatch.pdf. Last accessed on April 12, 2018.
- James JS. New kind of antiretroviral, KP-1461; clinical trial recruiting. Interview with Stephen Becker, M.D. AIDS Treat News. 2007 Jul-Sep; 423: 3-7. Available at: http://www.aidsnews.org/2007/10/kp-1461.html. Last accessed on April 12, 2018.
- Murakami E, Basavapathruni A, Bradley W, and Anderson KS. Mechanism of action of a novel viral mutagenic covert nucleotide: molecular interactions with HIV-1 reverse transcriptase and host cell DNA polymerases. Antiviral Res. 2005 Jul; 67(1): 10-7. Available at: http://www.vdapharma.com/s/2005-Mechanistic-studies-on-KP-1212.pdf. Last accessed onApril 12, 2018. [Archived at WebCite]
- 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 April 12, 2018.
- Koronis Pharmaceuticals. An open-label, multicenter, mechanism validation study to evaluate the safety, efficacy and tolerability of KP-1461 as monotherapy for 124 days in antiretroviral-experienced, HIV-1-infected subjects. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 18, 2007. NLM Identifier: NCT00504452. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00504452. Last accessed on April 12, 2018.
- Koronis Pharmaceuticals. A double-blind, placebo-controlled, dose escalation study of the safety, tolerability, and pharmacokinetics of multiple oral doses of KP-1461 in HIV+ adults who have failed two or more highly active antiretroviral regimens (HAART). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 9, 2005. NLM Identifier: NCT00129194. Available at: https://clinicaltrials.gov/show/NCT00129194. Last accessed on April 12, 2018.
Last Reviewed: January 17, 2019