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 rintatolimod?
Rintatolimod is an investigational drug that is categorized as a biological response modifier.2 Biological response modifiers (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function.3,4
Rintatolimod was studied for its ability to delay re-emergence of HIV during structured treatment interruptions of antiretroviral therapy (ART). A structured treatment interruption is a planned break from treatment, for example, ART. Structured interruption of ART is not recommended outside of controlled clinical trials.5,6
Also, rintatolimod has been studied for various non-HIV-related uses, including to treat chronic fatigue syndrome and cancer and to boost the body’s immune response to a flu vaccine.7-10
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.11
- 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.11
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.11
In what phase of testing is rintatolimod?
Rintatolimod for HIV treatment has been studied in Phase II clinical trials.2
What are some studies on rintatolimod?
Study Name: AMP 720
Location: United States
Participants: HIV-infected adults who had taken HIV medicines before entering the study (treatment-experienced). Participants’ HIV levels were under control, with a viral load level (the amount of HIV in the blood) of less than 50 copies/mL while on antiretroviral therapy (ART). Additionally, participants had a CD4 count greater than 400 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. The CD4 count of a healthy person ranges from 500 to 1,600 cells/mm3.)
Purpose: The purpose of this study was to evaluate whether rintatolimod could extend the time people could stay off HIV medicines during structured interruptions of ART (planned breaks from treatment) before their HIV began to rebound. (A rebound is when there are detectable levels of HIV in the blood after a period of undetectable levels.)
Study Design: During this study, up to three structured interruptions of ART were planned over a 64-week period. The participants were divided into two groups. One group received rintatolimod by intravenous injection twice weekly during the structured interruptions of ART. The other group (the control group) did not receive rintatolimod during the structured interruptions of ART. The structured interruptions of ART were stopped once a participant’s viral load rose to certain detectable levels.
- In this study, during the first structured interruption of ART, participants receiving rintatolimod were able to stay off HIV medicines while maintaining controlled viral load levels for longer periods of time than participants in the control group. The average duration of the first structured treatment interruption of ART in participants receiving rintatolimod was 27 weeks, whereas it was 13 weeks for participants in the control group.
- CD8 T lymphocytes (a type of immune cell that recognizes and destroys cells infected with microorganisms such as bacteria or viruses) increased more in participants receiving rintatolimod than in participants in the control group.
- In terms of safety, side effects associated with rintatolimod were described as being generally mild.5,6
Another Phase II study of rintatolimod (known as AMP 719) was also planned to take place. In AMP 719, investigators were planning to study the effectiveness of adding twice weekly rintatolimod to ART in people whose HIV medicines weren’t controlling their HIV infection. This study, however, was stopped and was not completed.12
What side effects might rintatolimod cause?
In the Phase II study looking at the use of rintatolimod during structured interruptions of ART, side effects were generally mild and cleared up without treatment.6
Because rintatolimod is still being studied, information on possible side effects of the drug is not complete. As testing of rintatolimod continues, additional information on possible side effects will be gathered.
Where can I get more information about clinical trials studying rintatolimod?
More information about rintatolimod-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 rintatolimod. 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.11
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/38640-92-5. Last accessed on July 7, 2015.
- 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 July 7, 2015.
- AIDS Clinical Trials Group (ACTG) Network website. Glossary of HIV-Related Terms. Definition for Biological Response Modifier (BRM). Available at: https://actgnetwork.org/sites/default/files/files/glossary-July-2008.doc. Last accessed on July 7, 2015.
- HealthHIV website. HIV Glossary of Terms. Definition for Biological Response Modifier (BRM). Available at: http://www.healthhiv.org/modules/info/glossary_of_hiv_terms.html. Last accessed on April 16, 2014.
- Hemispherx Biopharma. The Role of Ampligen in Strategic Therapeutic Intervention (STI) of Highly Active Anti-Retroviral Therapy (HAART): A Multi-Center, Randomized, Controlled Study of Ampligen Potentiation of the HAART-Free Interval. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 6, 2002. NLM Identifier: NCT00035893. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00035893. Last accessed on July 7, 2015.
- Blick G, Greiger-Zanlungo P, Strayer DR, Mitchell WM, Carter WA. Interim Results of AMP720: A Phase IIb Prospective, Randomized, Controlled Study Evaluating the Immunomodulatory Role of Ampligen (Poly I:Poly C12U) Against HIV During STI. 2nd International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment; July 13-16, 2003; Paris, France. Abstract 596. Available at: https://www.iasociety.org/Abstracts/A10016.aspx. Last accessed on July 7, 2015.
- Strayer DR, Carter WA, Stouch BC, et al. A Double-Blind, Placebo-Controlled, Randomized, Clinical Trial of the TLR-3 Agonist Rintatolimod in Severe Cases of Chronic Fatigue Syndrome. PLoS One. 2012;7(3):e31334. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303772/. Last accessed on July 7, 2015.
- University of Washington. Phase I-II Study of HER2 Vaccination With Poly(I) • Poly(C12U) (Ampligen®) as an Adjuvant in Optimally Treated Breast Cancer Patients. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 16, 2011. NLM Identifier: NCT01355393. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01355393. Last accessed on July 7, 2015.
- Pawel Kalinski. Randomized Phase I/II Evaluation of Neoadjuvant Administration of a Chemokine-Modulatory Regimen in Patients With Recurrent Resectable Colorectal Cancer. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on February 29, 2012. NLM Identifier: NCT01545141. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01545141. Last accessed on July 7, 2015.
- Hemispherx Biopharma. A Phase I/II, Two-Staged, Single-Center, Randomized, Double-Blind, Antibody Titer Study to Assess Immunogenicity and Safety of FluMist® Intranasal Influenza Vaccine Administered With and Without a TLR-3 Agonist, Ampligen®. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 2, 2012. NLM Identifier: NCT01591473. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01591473. Last accessed on July 7, 2015.
- 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 July 7, 2015.
- Hemispherx Biopharma. A Multi-Center, Randomized, Controlled Study of the Biological Actions of Ampligen as an Adjunct to HAART in HIV Disease. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on May 3, 2002. NLM Identifier: NCT00035581. Available at: https://www.clinicaltrials.gov/ct2/show/NCT00035581. Last accessed on July 7, 2015.
Last Reviewed: September 14, 2015