Emtricitabine/Tenofovir Alafenamide as Salvage ART
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02556333|
Recruitment Status : Terminated
First Posted : September 22, 2015
Results First Posted : October 17, 2017
Last Update Posted : November 14, 2017
HIV attacks the immune system. Antiretroviral therapy (ART) is a combination of drugs used for treating HIV infection. For some people, ART drugs stop working against their HIV. Researchers want to see if a different form of the drug tenofovir (an ART drug currently approved by the FDA), combined with another drug, may help people whose HIV is resistant to ART. This combination pill is called F/TAF
To study the safety and efficacy of the drug F/TAF, when used with other ART, for people whose HIV infection has been hard to control with available medicines.
People age 14 years and older who have HIV infection and are enrolled in the DOTCOM (14-I-0009) protocol.
Participants will be screened with physical exam, medical history, and blood and urine tests.
Participants will stay in the hospital for at least 10 days. For the first 9 days, they will take F/TAF by mouth along with their usual ART drugs.
In the hospital, they will repeat the screening tests.
Participants will have a DEXA scan, an x-ray that measures calcium and other minerals in the bones. Participants will lie on a soft table while the scanner passes over the lower spine and hips.
Participants will get a supply of F/TAF and some new ART drugs to take at home.
Participants will have follow-up visits in 1, 2, 4, 8, and 12 weeks. After the 12-week visit, they will come back about every 3 months for about 1 year.
At these visits, participants will repeat the screening tests. They will discuss any problems taking their ART drugs. They may have another DEXA scan.
|Condition or disease||Intervention/treatment||Phase|
|HIV||Drug: FTC/TAF||Phase 2|
Despite the success of antiretroviral therapy (ART), a subset of HIV-1-infected patients have uncontrolled viremia, multiple drug class resistance, and limited treatment options. Tenofovir disoproxil fumarate (TDF) forms part of most ART regimens, however its long-term use is associated with renal tubulopathy and reduced bone mineral density. Viral mutations (eg, K65R, multiple thymidine analog mutations (TAMs) can confer resistance or reduced susceptibility to TDF.
Tenofovir alafenamide (TAF) is an investigational oral prodrug of tenofovir. When compared to TDF, TAF demonstrated lower plasma tenofovir concentrations and more potent antiviral activity at approximately one-tenth of the dose. TAF has the advantage of reduced tenofovir exposure to the renal tubules and bone, potentially resulting in fewer kidney and bone effects. As with TDF, TAF has potent activities against hepatitis B virus (HBV), and may be a treatment option for patients with HIV/HBV co-infections. Phase 2 trials have demonstrated the non-inferiority of TAF to TDF in treating HIV-1 infection in ART-naive patients. Smaller reductions in bone mineral density were measured with TAF than TDF. The most common adverse events were nausea and diarrhea.
This single-arm, single-site, open-label trial will explore the safety and efficacy of TAF in a fixed combination with emtricitabine (FTC) (F/TAF, Gilead Sciences Inc.) as part of a salvage antiretroviral regimen for HIV-1-infected adults and adolescents (greater than or equal to 14 years) who experienced virologic failure. The study will recruit patients who have failed TDF-containing regimens or cannot take TDF (due to resistance mutations or risk of renal injury) and for whom abacavir/lamivudine (ABC/3TC) is not an optimal alternative. Eligible patients will begin 9 days of inpatient directly observed therapy (DOT) with F/TAF plus their pre-enrollment background regimen. On Day 10, patients will switch to F/TAF plus OBT while waiting for the results of Day 10 HIV RNA results. Patients with an HIV RNA decline of <0.5 log10 from Day 1 to Day 10 will discontinue F/TAF, end their study participation, and continue OBT (with TDF/FTC or ABC/3TC in place of F/TAF, as appropriate) under the 14-I-0009 protocol. Patients with a greater than or equal to 0.5 log10 decline in HIV RNA will continue on F/TAF + OBT for 48 weeks, with periodic outpatient assessments of adherence, safety, renal function, bone mineral density, HIV RNA, and CD4 T cell counts. Switching of one or more drugs in an ART regimen due to inadequate viral response will require inpatient DOT under 14-I-0009.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety and Efficacy of Emtricitabine/Tenofovir Alafenamide as Part of Salvage Antiretroviral Regimens in Patients With Uncontrolled Viremia and Drug-Resistant HIV Infection|
|Study Start Date :||September 16, 2015|
|Actual Primary Completion Date :||August 16, 2016|
|Actual Study Completion Date :||August 16, 2016|
Emtricitabine 200mg/tenofovir alafenamide 25mg (FTC/TAF) tablet to be given orally once daily to be added to a failing regimen for 10 days. If HIV RNA decline by >= 0.5 log copies/mL, patient will continue on FTC/TAF with a new antiretroviral regimen for 48 weeks. If < 0.5 log copies/mL decline, patient will be taken off FTC/TAF.
Tenofovir alafenamide (TAF) is an investigational oral prodrug of tenofovir. This trial will explore the safety and efficacy of TAF in a fixed combination with emtricitabine (FTC) (F/TAF, Gilead Sciences Inc.) as part of a salvage antiretroviral regimen for HIV-1-infected adults and adolescents (greater than or equal to 14 years) who experienced virologic failure.
Other Name: Emtricitabine 200mg/tenofovir alafenamide 25 mg (F/TAF)
- HIV RNA Change From Baseline to Day 10 [ Time Frame: 10 days ]An HIV RNA decline of >=0.5 log by day 10 will be considered to be an adequate virologic response, to proceed to the second phase of the study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02556333
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Alice Pau, Pharm.D.||National Institute of Allergy and Infectious Diseases (NIAID)|