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 romidepsin?
Romidepsin (brand name: Istodax) is a drug that has been approved by FDA for the treatment of certain types of cancer. It is currently being studied to see if it could be effective as part of a strategy to cure HIV infection.5-10
Currently, there is no cure for HIV infection. One of the main obstacles to curing HIV infection is that the virus can remain hidden and inactive (latent) inside certain cells of the immune system (such as resting CD4 T cells) for many months or even years. While HIV is in this latent state, the immune system cannot recognize the virus, and antiretroviral therapy (ART) has no effect on it. (ART is the recommended treatment for HIV infection and involves using a combination of different antiretroviral [ARV] drugs to prevent HIV from replicating.)11,12
Romidepsin belongs to a general class (group) of HIV drugs called latency-reversing agents.2 There are different types of latency-reversing agents. Romidepsin is a type of latency-reversing agent called a histone deacetylase (HDAC) inhibitor.13
How do latency-reversing agents work?
Latency-reversing agents reactivate (turn back on) latent HIV within resting CD4 T cells. When latent HIV is reactivated, it is once again able to produce new virus and multiply (replicate). It is hoped that after latent HIV is reactivated, the CD4 T cells in which the virus was hiding are more likely to die off on their own or be recognized and killed by the body’s immune system.12,13
In addition, any new virus that is produced during reactivation can then be prevented from infecting other cells with the use of ongoing ART.12,13 Recent research has shown that additional therapies, together with latency-reversing agents, may be needed to fully eliminate latent HIV from the body.13
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.14
- 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.14
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.14 (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 romidepsin?
Romidepsin is being studied in Phase II clinical trials.5,10
What are some studies on romidepsin?
Study Names: REDUC trial; NCT02092116
Sponsor: Bionor Immuno AS
- Participants were HIV-infected adults who were on ART at the start of the study and who had been on ART for at least 1 year.
- Participants had viral load levels (the amount of HIV in a blood sample) of less than 50 copies/mL for at least 1 year.
- Participants had CD4 counts of at least 500 cells/mm3, and their lowest ever CD4 counts in the past 2 years were no less than 200 cells/mm3. (A CD4 count is a laboratory test that measures the number of CD4 cells—a type of immune cell—in a sample of blood and is an important indicator of immune function.)
Purpose: The REDUC trial was a 2-part study. Part A was designed to find a safe and effective dose of romidepsin to use in the second part of the study. Part B was designed to evaluate (1) the safety of the investigational therapeutic vaccine Vacc-4x when combined with romidepsin, and (2) whether this drug combination could reduce the amount of latent HIV in the body and control viral load levels during a planned break from ART.7,15
Study Names: ACTG 5315; NCT01933594
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Location: United States
- Participants are HIV-infected adults who have been on an ART regimen containing 2 or more nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz (brand name: Sustiva), raltegravir (brand name: Isentress), or dolutegravir (brand name: Tivicay) for at least 90 days before starting the study.
- Participants have had viral load levels of less than 50 copies/mL for at least 1 year before starting the study.
- Participants have had CD4 counts of at least 300 cells/mm3 within a 1- to 3-month period before starting the study.
Purpose: The purpose of this study is to look at the safety of single and multiple doses of romidepsin and to determine the effectiveness of single and multiple romidepsin doses in reactivating latent HIV within resting CD4 T cells.8
* This study is currently recruiting participants.
Study Identifiers: ROADMAP; NCT02850016
Sponsor: Rockefeller University
Locations: Denmark, Germany, United States
- Participants are HIV-infected adults who have been receiving ART for at least 24 months.
- Participants who are on an ART regimen containing a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, or the drug cobicistat must be willing to switch to an ART regimen that contains an integrase inhibitor before starting the study.
- Participants have had viral load levels of less than 50 copies/mL for at least 18 months and have CD4 counts greater than 500 cells/mm3 at the start of the study.
Purpose: The purpose of this study is to compare the effectiveness of romidepsin plus the investigational antibody drug 3BNC117 to the effectiveness of romidepsin administered alone in controlling viral load after a treatment interruption. (A treatment interruption is a planned break from HIV medicines to evaluate how well an investigational drug can maintain control of a participant’s viral load during a clinical trial.)10
* This study is currently recruiting participants.
Study Names: BIOSKILL; EudraCT 2015-003186-28
Sponsor: Bionor Pharma ASA
Locations: Australia, Europe, United States
- Participants are HIV-infected adults who have been receiving ART continuously for at least 3 years.
- Participants have maintained viral load levels of less than 20 copies/mL and have CD4 counts of 500 cells/mm3 or more at the start of the study.
- Participants’ lowest ever CD4 counts were 250 cells/mm3 or above.
Purpose: The purpose of this study is to evaluate the safety and effectiveness of the combined use of Vacc-4x and romidepsin. The researchers will measure the effects of Vacc-4x and romidepsin on viral load, latent HIV, and the body’s immune responses.5
* This study is ongoing.
For more details on the studies listed above, see the Health Professional version.
Another study, the BCN02-Romi trial (NCT02616874), is a Phase I trial that is looking at the use of an investigational therapeutic vaccine called MVA.HIVconsv in combination with romidepsin in participants who have already received investigational therapeutic vaccines during a separate trial.9,16
What side effects might romidepsin cause?
In Part A of the REDUC trial (NCT02092116) discussed under the previous question, all romidepsin-related side effects were mild in severity and resolved within a few days. The most common side effects related to romidepsin were abdominal symptoms (such as nausea, stomach growling, and abdominal pain) and fatigue. Some mild changes in white blood cell counts and T cell counts were seen.15
In Part B of the REDUC trial, the majority of side effects were mild in severity. Side effects associated with romidepsin included fatigue and nausea. One side effect associated with romidepsin—mild hair loss—did not resolve by the end of the study. Side effects related to Vacc-4x plus the adjuvant and to the treatment interruption also occurred.17
Because romidepsin is still being studied, information on possible side effects of the drug is not complete. As testing of romidepsin continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying romidepsin?
More information about romidepsin-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.14
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/128517-07-7. Last accessed on February 16, 2017.
- Treatment Action Group website. Research Toward a Cure Trials. Available at: http://www.treatmentactiongroup.org/cure/trials. Last accessed on February 16, 2017.
- Celgene Corporation website. Therapies. Available at: https://www.celgene.com/therapies/. Last accessed on February 16, 2017.
- Masetti R, Serravalle S, Biagi C, and Pession A. The Role of HDACs Inhibitors in Childhood and Adolescence Acute Leukemias. J Biomed Biotechnol. Vol 2011; Article ID 148046. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026992/pdf/JBB2011-148046.pdf. Last accessed on February 16, 2017.
- EU Clinical Trials Register. EudraCT Number: 2015-003186-28; BIOSKILL: Studying Vacc-4x, an HIV therapeutic vaccine, an assessment of immune-mediated anti-viral effects, when administered with adjuvant GM-CSF prior to HIV latent reservoir activation by the HDAC inhibitor, romidepsin. Available at: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003186-28/DK. Last accessed on February 16, 2017.
- Celgene Corporation. ISTODAX – romidepsin: Full Prescribing Information, October 2014. DailyMed. Available at:https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=03b39d40-90fe-11df-9de6-0002a5d5c51b. Last accessed on February 16, 2017.
- Bionor Immuno AS. An Open Phase I/IIa Study to Evaluate the Safety and Effect of Therapeutic HIV-1 Immunization Using Vacc-4x + rhuGM-CSF, and HIV-1 Reactivation Using Romidepsin, on the Viral Reservoir in Virologically Suppressed HIV-1 Infected Adults on cART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 3, 2014. NLM Identifier: NCT02092116. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02092116. Last accessed on February 16, 2017.
- National Institute of Allergy and Infectious Diseases (NIAID). A Phase I/II Study of Single Dose Romidepsin in HIV-Infected Adults With Suppressed Viremia on Antiretroviral Therapy to Assess Safety, Tolerability, and Activation of HIV-1 Expression. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on August 28, 2013. NLM Identifier: NCT01933594. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01933594. Last accessed on February 16, 2017.
- IrsiCaixa. An Open Label Phase I Trial to Evaluate the Safety and Effect of HIVconsv Vaccines in Combination With Histone Deacetylase Inhibitor Romidepsin on the Viral Rebound Kinetic After Treatment Interruption in Early Treated HIV-1 Infected Individuals (BCN02-Romi). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 9, 2015. NLM Identifier: NCT02616874. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02616874. Last accessed on February 16, 2017.
- Rockefeller University. A Phase 2a, Randomized Study of Romidepsin With or Without 3BNC117 to Evaluate the Effects on the HIV-1 Reservoir (ROADMAP). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on July 26, 2016. NLM Identifier: NCT02850016. Available at: https://clinicaltrials.gov/ct2/show/NCT02850016. Last accessed on February 16, 2017.
- National Institute of Allergy and Infectious Diseases (NIAID): News Release, dated June 16, 2009. NIAID Invites Applications to Conduct Basic Research on HIV Persistence: Studies Key to Search for a Cure. Available at:https://wayback.archive-it.org/7761/20160907080510/http://www.niaid.nih.gov/news/newsreleases/Archive/2009/Pages/HIV_persistence.aspx. Last accessed on February 16, 2017.
- Siliciano RF, Greene WC. HIV Latency. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a007096. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234450/. Last accessed on February 16, 2017.
- Rasmussen TA, Tolstrup M, Winckelmann A, Ostergaard L, Søgaard OS. Eliminating the latent HIV reservoir by reactivation strategies. Hum Vaccin Immunother. 2013 Apr 1;9(4):790-799. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903897/. Last accessed on February 16, 2017 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 February 16, 2017.
- Søgaard OS, Graversen ME, Leth S, et al. The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo. PLoS Pathog. 2015 Sep; 11(9): e1005142. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575032/. Last accessed on February 16, 2017.
- IrsiCaixa. Safety and Immunogenicity of ChAdV63.HIVconsv and MVA.HIVconsv Candidate HIV-1 Vaccines in Recently HIV-1 Infected Individuals With Early Viral Suppression After Initiation of Antiretroviral Therapy (HAART). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 4, 2012. NLM Identifier: NCT01712425. Available at: https://clinicaltrials.gov/ct2/show/NCT01712425. Last accessed on February 16, 2017.
- Leth S, Schleimann MH, Nissen SK, et al. Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV. 2016 Oct;3(10):e463-72. Available at: http://www.natap.org/2016/HIV/PIIS23523018163005581.pdf. Last accessed on February 16, 2017.
Last Reviewed: February 16, 2017