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.
What is INCB-9471?
INCB-9471 is an investigational drug that has been studied for the treatment of HIV infection.
INCB-9471 belongs to a class (group) of HIV drugs called entry and fusion inhibitors.2 Entry and fusion inhibitors block HIV from getting into and infecting certain cells of the immune system. This prevents HIV from multiplying and can reduce the amount of HIV in the body.
INCB-9471 works by attaching to a protein on the surface of the immune cells. The protein is called the CCR5 co-receptor. When INCB-9471 attaches to the CCR5 co-receptor, certain strains of HIV—called R-5 tropic virus—cannot attach to, enter, or infect the cell.3
Research may prove that INCB-9471 is a safe and effective option for treating people with R5-tropic virus, including those for whom other entry and fusion inhibitors, such as maraviroc (brand name: Selzentry), are not working.4
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.5
- 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.5
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.5
In what phase of testing is INCB-9471?
INCB-9471 has been studied in Phase II clinical trials.2 In 2008, the company developing INCB-9471 announced that it was no longer actively studying INCB-9471 and was seeking a partner company to develop the drug.3
What are some studies on INCB-9471?
Study Names: Not available
Location: Not available
Participants: HIV-infected adults who had R5-tropic virus. Some of participants had never taken HIV medicines before entering the study (also called treatment-naive), and others had taken HIV medicines previously (also called treatment-experienced). The treatment-experienced adults had been off therapy for at least 3 months.
Purpose: The purpose of this study was to look at the safety, antiviral activity, and drug properties of INCB-9471.
Study Design: Participants were assigned to receive either 200 mg of INCB-9471 given once daily without any other HIV medicines (also called monotherapy) or placebo over 14 days. (A placebo is an inactive drug that is identical in appearance to the active drug being studied.)
- In this study, INCB-9471 showed substantial antiviral activity against R5-tropic HIV.
- Prolonged anti-HIV activity was apparent, with viral load levels decreasing from the beginning of the study and continuing to remain reduced 2 weeks past the last dose of INCB-9471. (Viral load is the amount of HIV in a blood sample.)
- In terms of safety, INCB-9471 was generally safe. No serious side effects or study drop-outs were reported.6-8
Study Names: NCT00393120; INCB 9471-201
Location: United States
Participants: HIV-infected, treatment-naive or –experienced adults who had R5-tropic virus. The treatment-experienced adults had been off therapy for at least 3 months.
Purpose: The purpose of this study was to look at the safety, effectiveness, and drug properties of INCB-9471.
Study Design: Participants were assigned to receive one of three different doses of INCB-9471 (100 mg, 200 mg, or 300 mg) given as once daily monotherapy for 14 days or to receive placebo for 14 days.
- In this study, INCB-9471 given at the two higher dose strengths led to significant reductions in participants’ viral loads after 14 days of treatment.9,10
What side effects might INCB-9471 cause?
In the first study discussed under the previous question, which was a 14-day Phase IIa study of INCB-9471 in HIV-infected adults, INCB-9471 was generally considered safe. Some mild side effects that occurred that might be related to INCB-9471 treatment included constipation, diarrhea, nausea, headache, hiccups, and rash.6-8
In previous studies of INCB-9471 in healthy study participants, some common side effects that occurred were headache, diarrhea, sore throat, and cold symptoms.11,12
Information on possible side effects of the drug is not complete. As testing of INCB-9471 continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying INCB-9471?
More information about INCB-9471-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.
I am interested in participating in a clinical trial of INCB-9471. 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.5
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/925701-76-4. Last accessed on January 3, 2016.
- National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development. Available at: http://chemdb.niaid.nih.gov/DrugDevelopmentHIV.aspx. Last accessed on January 3, 2016.
- Incyte Corporation: Press Release, dated March 17, 2008. Incyte to Provide Update on Clinical Programs at Cowen Health Care Conference. Available at: http://investor.incyte.com/phoenix.zhtml?c=69764&p=irol-newsArticle&ID=1119174&highlight. Last accessed on January 3, 2016.
- Shin N, Solomon K, Zhou N, et al. Identification and Characterization of INCB9471, an Allosteric Noncompetitive Small-Molecule Antagonist of C-C Chemokine Receptor 5 with Potent Inhibitory Activity against Monocyte Migration and HIV-1 iInfection. J Pharmacol Exp Ther. 2011 Jul; 338(1):228-39. Available at: http://jpet.aspetjournals.org/content/338/1/228.long. Last accessed on January 3, 2016.
- 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 January 3, 2016.
- Incyte Corporation: Press Release, dated July 24, 2007. Phase IIa Study Results Demonstrate that Once-Daily 200 mg Dosing of INCB9471 Provided Potent and Prolonged Antiviral Activity in HIV-Infected Patients. Accessed April 24, 2013. Available at: http://investor.incyte.com/phoenix.zhtml?c=69764&p=irol-newsArticle&ID=1029620&highlight=. Last accessed on January 3, 2016.
- Cohen C, DeJesus E, Mills A, et al. Potent antiretroviral activity of the once-daily CCR5 antagonist INCB009471 over 14 days of monotherapy. Abstract presented at: 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Abstract TUAB106. Available at: https://www.aids2014.org/Default.aspx?pageId=11&abstractId=200700303. Last accessed on January 3, 2016.
- Cohen C, DeJesus E, Mills A, et al. Potent Antiretroviral Activity of the Once-Daily CCR5 Antagonist INCB009471 Over 14 Days of Monotherapy. 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Levin: New Incyte CCR5 Drug Shows Good Activity: 14 day monotherapy study; Conference reports for National AIDS Treatment Advocacy Project (NATAP); 2007. Available at: http://www.natap.org/2007/IAS/IAS_19.htm. Last accessed on January 3, 2016.
- Erickson-Viitanen S, Abremski K, Solomon K, et al. Co-Receptor Tropism, ENV Genotype, and in vitro Susceptibility to CCR5 Antagonists During a 14-Day Monotherapy Study with INCB9471. 15th Conference on Retroviruses and Opportunistic Infections (CROI); February 3-6, 2008; Boston, MA. Levin: Conference Reports for National AIDS Treatment Advocacy Project (NATAP); 2008. Available at: http://www.natap.org/2008/CROI/croi_74.htm. Last accessed on January 3, 2016.
- Incyte Corporation. A Randomized, Double-blind, Placebo-controlled Study Exploring the Safety, Tolerability, PK & Virological Effect of Once Daily Oral Dosing of INCB009471 as Monotherapy for 14 Days in ARV-naïve/Limited ARV-experienced, HIV-1 Infected Pts. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 24, 2006. NLM Identifier: NCT00393120. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00393120. Last accessed on January 3, 2016.
- Troy S, Emm T, Yeleswaram S, et al. Single and Multiple Dose Pharmacokinetics of INCB9471, a Potent Antagonist of CCR5 Co-Receptor. Poster presented at: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2007; Chicago, IL. Poster H-1034. Available from Incyte Corporation at: http://library.corporate-ir.net/library/69/697/69764/items/261807/Poster%20H-1034.pdf. Last accessed on January 3, 2016.
- Troy S, Emm T, Yeleswaram S, et al. Effect of Ritonavir on the Pharmacokinetics of INCB9471, a Potent Antagonist of CCR5 Co-Receptor. Poster presented at: 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); September 17-20, 2007; Chicago, IL. Poster H-1035. Available from Incyte Corporation at: http://library.corporate-ir.net/library/69/697/69764/items/261808/Poster%20H-1035.pdf. Last accessed on January 3, 2016.
Last Reviewed: January 3, 2016