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 KP-1461?
KP-1461 is an investigational drug that has been studied for the treatment of HIV infection.
KP-1461 belongs to a class (group) of HIV drugs called nucleoside reverse transcriptase inhibitors (NRTIs).2 Typically, NRTIs block an HIV enzyme called reverse transcriptase, which prevents HIV RNA from being converted to HIV DNA. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) Preventing the RNA-to-DNA conversion step stops HIV from replicating.
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 mutations into the newly created HIV DNA. These mutations harm HIV rather than help it survive. In theory, KP-1461 causes so many mutations to build up in HIV over time that the virus cannot continue to live and multiply 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 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 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
Location: United States and Puerto Rico
- Participants were HIV-infected adults who had previously taken HIV medicines before entering the study.
- Participants had previously received antiretroviral therapy (ART) that did not control their viral load (the amount of HIV in a blood sample) and/or had drug resistance to multiple classes of HIV medicines. (Drug resistance is when a person’s HIV mutates [changes form] 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 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 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 HIV-infected participants who had previously tried 2 or more ART regimens that did not control their viral loads.9
What side effects might KP-1461 cause?
In the Phase IIa study (NCT00504452) discussed under the previous question, 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
Because KP-1461 is still being studied, information on possible side effects of the drug 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 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?
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: http://chem.sis.nlm.nih.gov/chemidplus/rn/815588-85-3. Last accessed on February 1, 2017.
- 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 February 1, 2017.
- 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: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552433/. Last accessed on February 1, 2017.
- 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 February 1, 2017.
- 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 February 1, 2017.
- 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 on February 1, 2017.
- National Institutes of Health (NIH). NIH Clinical Research Trials and You. Available at: http://www.nih.gov/health-information/nih-clinical-research-trials-you. Last accessed on February 1, 2017.
- 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 February 1, 2017.
- 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 February 1, 2017.
Last Reviewed: February 1, 2017