Emtricitabine/Tenofovir Alafenamide as Salvage ART

NCT02556333 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 15020115-I-0201
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Background: 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 Objective: 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. Eligibility: People age 14 years and older who have HIV infection and are enrolled in the DOTCOM (14-I-0009) protocol. Design: 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.

Conditions

HIV

Keywords

TAF; F/TAF; antiretroviral therapy; TDF; directly observed therapy

Outcome Measures

Primary Outcomes (1)

• HIV RNA Change From Baseline to Day 10

  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.

  10 days

Study Arms (1)

FTC/TAF

EXPERIMENTAL

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.

Drug: FTC/TAF

Interventions

FTC/TAF DRUG

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.

Also known as: Emtricitabine 200mg/tenofovir alafenamide 25 mg (F/TAF)

FTC/TAF

Eligibility Criteria

• Age: 14 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 14 years
• Documented HIV-1 infection (written documentation of positive standard ELISA or rapid HIV-1/HIV-2 antibody test with confirmatory Western Blot, or documentation of repeated HIV RNA of \> 1,000 copies/mL)
• Concurrent enrollment in the DOTCOM (14-I-0009) protocol
• For females of childbearing potential, willingness to use effective contraception for the duration of the study
• Willingness to be hospitalized for 10-15 days (with potential for day passes)
• Willingness to have blood samples stored for future research that may include genetic testing
• Multiple ART failure as defined by at least one of the following criteria:
• HIV RNA \> 1000 copies/mL and documented virologic failure on at least 1 prior ART regimen and at least 2 consecutive HIV RNA plasma measurements of \> 1,000 copies/mL, including the last documented value, while on the currently prescribed ART regimen for at least 6 months; or
• Documented extensive resistance to at least 3 antiretroviral (ARV) drug classes, and persistent plasma viremia (HIV RNA \> 1,000 copies/mL for \> 6 months) despite multiple regimen changes. The patient may be enrolled even if they have been prescribed their current regimens for less than 6 months.
• Where neither TDF nor ABC are optimal NRTI options as defined by at least one of the following criteria:
• Presence of the M184V mutation plus TDF-associated resistance mutations based on genotypic/phenotypic testing, specifically K65R alone, or with TAMs (such as 41L, 67N, 70R, 210W, 215Y/F, or 219Q/E) with or without other NRTI-associated mutations; or
• FTC/TDF is not considered an option due to impaired renal function (eGFR by Cockroft-Gault equation \[eGFR(CG)\]=30-60 mL/min), or risk of renal impairment because of conditions such as uncontrolled hypertension, diabetes mellitus, or history of renal toxicity while receiving a TDF-based regimen; and where ABC/3TC is contraindicated (ie, presence of HLA B\*5701 allele or history of hypersensitivity reaction to ABC), or is a suboptimal option (eg, presence of ABC-associated resistance mutation(s) or in patients with HBV co-infection).

You may not qualify if:

• Severe renal impairment (eGFR(CG) \<30 mL/min)
• Acute medical illness stemming from a significant co-morbidity (eg, malignancy requiring chemotherapy, treatment of an acute opportunistic infection or acute renal failture). Enrollment may be deferred up to 3 months to allow a condition to resolve or stabilize.
• Pregnancy; however if a patient becomes pregnant while enrolled in the protocol, she may continue participation throughout her pregnancy.
• Breastfeeding
• Concomitant use of one of the following medications: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bisphosphonate, St. John s wort, echinacea, milk thistle, sho-saiko-to, and probenecid.
• Any illness or condition that, in the investigator's opinion, may substantially increase the risk of participation in the study, or compromise the scientific objectives.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Dombrowski JC, Kitahata MM, Van Rompaey SE, Crane HM, Mugavero MJ, Eron JJ, Boswell SL, Rodriguez B, Mathews WC, Martin JN, Moore RD, Golden MR. High levels of antiretroviral use and viral suppression among persons in HIV care in the United States, 2010. J Acquir Immune Defic Syndr. 2013 Jul 1;63(3):299-306. doi: 10.1097/QAI.0b013e3182945bc7.

  PMID: 23572013 BACKGROUND

• Deeks SG, Gange SJ, Kitahata MM, Saag MS, Justice AC, Hogg RS, Eron JJ, Brooks JT, Rourke SB, Gill MJ, Bosch RJ, Benson CA, Collier AC, Martin JN, Klein MB, Jacobson LP, Rodriguez B, Sterling TR, Kirk GD, Napravnik S, Rachlis AR, Calzavara LM, Horberg MA, Silverberg MJ, Gebo KA, Kushel MB, Goedert JJ, McKaig RG, Moore RD. Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America. Clin Infect Dis. 2009 Nov 15;49(10):1582-90. doi: 10.1086/644768.

  PMID: 19845473 BACKGROUND

• Ezinga M, Wetzels JF, Bosch ME, van der Ven AJ, Burger DM. Long-term treatment with tenofovir: prevalence of kidney tubular dysfunction and its association with tenofovir plasma concentration. Antivir Ther. 2014;19(8):765-71. doi: 10.3851/IMP2761. Epub 2014 Feb 28.

  PMID: 24584104 BACKGROUND

MeSH Terms

Conditions

Directly Observed Therapy

Interventions

Emtricitabine; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Medication Adherence; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

The study was approved in late 2015, with the first and only patient enrolled in Jan 2016. The drug was approved in April 2016, which resulted in termination of the protocol.

Results Point of Contact

• Title: Alice Pau, Pharm.D., Staff Scientist (Clinical)
• Organization: National Institutes of Health, National Institute of Allergy and Infectious Diseases

apau@niaid.nih.gov

301-451-3740

Study Officials

• Alice Pau, Pharm.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2015
• First Posted: September 22, 2015
• Study Start: September 16, 2015
• Primary Completion: August 16, 2016
• Study Completion: August 16, 2016
• Last Updated: November 14, 2017
• Results First Posted: October 17, 2017

Record last verified: 2017-10-16

Locations

US (1)