• A5371: A Single-Arm, Open-Label, Pilot Study of Semaglutide for Non-Alcoholic Fatty Liver Disease (NAFLD), a Metabolic Syndrome with Insulin Resistance, Increased Hepatic Lipids, and Increased Cardiovascular Disease Risk (The SLIM LIVER Study)

    October 8, 2020 Alexis Sexton

    Short Title: The Slim Liver Study

    Brief Description: About 30-40% of people living with HIV have a condition called NAFLD, or non-alcoholic fatty liver disease.  NAFLD is caused by high levels of stored fat in the liver. Most people with NAFLD also have other complications like high cholesterol, obesity, increased belly fat or type 2 diabetes. These complications can lead to cardiovascular disease (any disease of the heart or blood vessels that can lead to a stroke or heart attack).  In fact, most of the health problems that are associated with NAFLD are related to these conditions of the heart or metabolism.  Without treatment, NAFLD can advance to more serious liver disease. By using a drug that can lower the level of stored fat in the liver, people living with HIV may be able to treat NAFLD and reduce their risk of cardiovascular disease and other complications.

    Purpose of this Study: The purpose of this study is to evaluate the safety and tolerability of a drug called semaglutide and to see if it can reduce the amount of fat stored in the liver.

    Requirements to Enter Study (things that must be true for you):

    • Living with HIV with 2 HIV viral loads less than 50 copies in the last year and a CD4 T-cell count of at least 200
    • On your current HIV medications for at least 24 weeks
    • Willingness to have MRI scans
    • Agree to use contraception/birth control methods (if needed)
    • Able to store semaglutide in a cool location
    • Be 18 years old or older
    • Be willing to sign the consent after discussion with the research staff
    • Be willing to give yourself an injection once a week

    Exclusion Criteria (things that cannot be true for you):

    • Hepatitis B or C Virus infection (not previously treated)
    • Any plans to change diet or exercise significantly during the study period
    • Breastfeeding, pregnancy, or plans to become pregnant while on study
    • Liver disease with cirrhosis
    • Current diabetes mellitus
    • Chronic pancreatitis
    • Prior gastric (stomach) surgery (lab band, gastric sleeve or gastric bypass surgery) or plans to undergo one of these surgeries in the near future
    • High alcohol use

    Treatment:

    • Semaglutide subcutaneous injection once weekly for 24 weeks.

    Procedures:

    • Blood tests at clinic visits
    • Stool collections
    • MRI scans
    • Adherence monitoring, physical function assessment, food diary, and questionnaires

    Duration of Study: Approximately 48 weeks

  • A5372: Drug-Drug Interactions Between Rifapentine and Dolutegravir in HIV/LTBI Co-Infected Individuals (RPT-DTG PK Study)

    September 1, 2020 Alexis Sexton

    The purpose of this research study is see if taking medications to prevent tuberculosis (TB) affect the drug levels in blood of a commonly used HIV medication called dolutegravir (DTG) and if an extra dose of DTG is needed during this TB preventive treatment. The other medicines, rifapentine (RPT) and isoniazid (INH), are drugs used to prevent active TB in people who have been exposed to TB. This study will also help us make sure that people tolerate the medicines and that they are safe when given together. In many countries, DTG is the recommended first-line treatment for HIV. DTG, RPT, and INH are proven beneficial treatments for people living with HIV and latent TB, but it is unclear whether these treatments work differently when taken together. Understanding how DTG interacts with the short-term treatment for latent TB (1HP) is very important for delivering both treatments effectively.

    Purpose of the Study:  To see if taking a medicine to treat TB called RPT, affects the levels of DTG (an HIV medicine) in the blood or not.

    Requirements to Enter Study:  This study is for people living with HIV between the ages of 18-65 and who either tested positive for the bacteria that causes tuberculosis (TB) or live in a country where TB infection occurs frequently. Participants must be taking dolutegravir as part of a three drug regimen to treat HIV and must have a viral load < 50 copies/ml.  In addition to these criteria, blood samples will be drawn for lab tests to check general health.  Participants will also need to weigh at least 40 kilograms and have either a chest x-ray or CT scan of their lungs to check for active TB disease.

    Treatment:  Participants will continue ART medications that include DTG and 2 nucleoside reverse transcriptase inhibitors for the entire study period.

    TB medication to prevent active TB disease will begin at entry into the study and include the RPT and a second medication used to treat TB called isoniazid (INH) along with daily vitamin B6, to decrease the risk of side effects from INH.

    The study will have two (2) groups. Group 2 will only open after the results from Group 1 are reviewed.

    Below are the medicines that you will take during the study depending on which Group you are in:

    Group 1

    • DTG 50 mg orally twice daily – about 12 hours apart
      • 1st dose will be taken in the morning; this will not be supplied by the study
      • 2nd dose will be taken in the evening; this will be supplied by the study for 4 weeks
    • 1HP: INH 300 mg + RPT 600 mg orally once daily (in the morning) for 4 weeks (supplied by the study)

    Group 2 (upon opening)

    • DTG 50 mg orally once daily (in the morning) (not supplied by the study)
    • 1HP: INH 300 mg + RPT 600 mg orally once daily (in the morning) for 4 weeks (supplied by the study)

    You will continue taking your existing ART drugs while on the study – your ART must include 2 NRTIs (excluding TAF) during the study. Your ART will not be provided by the study.

    You will also receive pyridoxine (vitamin B6) 25 or 50 mg with each dose of INH based on the current local, national, or international dosing guidelines.

    Because the blood draws on study visits will be dependent on the time you take the drugs, you will need to take your HIV drugs and drugs provided by the study (except second dose of DTG if you are in Arm 1) in the morning during the duration of the study. If you generally take your HIV drugs in the evening, you will need to switch to taking them in the morning for this study, including at least 3 days before the Day 0 visit. On the study visit days, you will hold on taking the drugs until you arrive at the clinic.

    Duration of Study:  Most people will be on this study for six weeks (4 weeks on study treatment and two weeks of follow-up). You may be on study up to 11 weeks if you have to have additional follow-up visits to check your viral load. There are 7 or 8 scheduled visits during this time.

  • A5312: The Early Bactericidal Activity of High Dose or Standard Dose Isoniazid among adult Participants with Isoniazid-Resistant or Drug Sensitive Tuberculosis

    August 31, 2020 Alexis Sexton

    This study is for participants who have pulmonary tuberculosis (TB), a bacterial infection in their lungs. Isoniazid (INH) is a drug commonly used to treat TB. Sometimes, the bacteria that cause TB can become resistant to INH, and then INH does not work as well at fighting the bacteria. This study will treat people with INH-resistant TB with different doses of INH to see if INH can still fight the bacteria if we just increase the dose.

    Purpose

    We will compare how well the drug works at higher doses for participants who have resistant TB to how well the drug works at regular doses for participants who have TB that is sensitive to the drug. The study will also compare the safety and tolerability of the different doses of INH.

    Study Stages

    If you join this study, you will need to be admitted to the hospital for at least 9 days. If you have not stopped taking INH you may need to be admitted for longer (up to 16 days in total) so that there is time for the INH to wash out of your body. While you are in the hospital, you will be asked to collect the sputum that you cough up in a container. Seeing how many bacteria are in the sputum you cough up will help us to know how well the medicine is working. After you are discharged from the hospital, you will come to the clinic 14 days later for a final visit.

    If you meet the eligibility requirements for the study, you will have a test to see if you have INH-resistant TB, and if it is low-level or high-level resistance. (With low-level resistance, the bacteria are not as resistant to INH as they are with high-level resistance.) You may also be asked to provide sputum for other types of resistance tests.

    Depending on the test result, you will be assigned to one of 3 groups:

    • If you have low-level INH resistance, you will either be referred to receive standard TB treatment outside of the study or be randomized (like a flip of a coin) to receive 5, 10 or 15 mg/kg INH once a day for 7 days. Randomized means that you have equal chance of being in any of these 3 groups. (Mg/kg, or milligrams per kilogram, means the amount of INH in milligrams you will receive for each kilogram you weigh.)
    • If your test shows no INH resistance, you will either be referred to receive standard TB treatment outside the study or you will receive 5 mg/kg INH once a day for 7 days.
    • If you have high-level resistance, you will either be referred to received standard TB treatment outside the study or you will be randomized to receive 15 or 20 mg/kg INH once a day for 7 days.

    INH will be provided for you. In addition, you must also take vitamin B6 once a day while taking INH, to help prevent possible side effects of INH. Vitamin B6 will also be provided to you. When you are finished taking study drug, you will be referred for full TB treatment outside the study.

    Inclusion Criteria:

    • New or current pulmonary TB
    • Adults between the ages of 18 and 65

    Exclusion Criteria

    • Known exposure to extensively resistant TB (XDR-TB)

    Duration of Study: About 23 days

    Total number of participants: Between 128 and 218

  • A5401: ACTIV-2 Outpatient Monoclonal Antibodies and Other Therapies

    July 21, 2020 Alexis Sexton

    Study Description:

    A master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with COVID-19. It begins with a phase II evaluation, followed by a transition into a larger phase III evaluation for promising agents.

    Why is this study being done?

    To rapidly and efficiently evaluate multiple potential therapeutics for COVID-19 in an outpatient setting.

    Who can join?

    • Ambulatory Adult (18 years or older)
    • Active SARS-CoV-2 infection <7 days prior to Entry
    • At least one typical COVID-19 symptom for <10 days prior to Entry, plus one the following symptoms present within 48 hours of entry:

    –Fever or feeling feverish, cough, shortness of breath at rest or with activity, sore throat, body or muscle pain, fatigue, headache, chills

    • Tailored per study agent requirements

    Duration of study: 28 days of intensive follow-up, followed by limited follow-up through 24 weeks.

     

    To find more information click here and to see our press release relating to this study click here.

  • A5300B:Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant Tuberculosis Participants (PHOENIx)

    February 20, 2020 Alexis Sexton

    This trial is in household contacts (HHC) at high risk for developing multidrug resistant tuberculosis (MDR-TB) which is an infection that does not get better with standard treatment for TB.  HHC means any person that  lives with, has lived with, or shared housekeeping duties in a home or the same place with a person (an Index Case) who has pulmonary MDR-TB (a lung infection or pneumonia with TB) and started treatment for MDR-TB within the past 90 days. It is also for people who have spent more than 4 hours indoors with the index case, during the week before they started MDR-TB treatment.

    High-risk household contacts are those with HIV or an immune system problem not from HIV like cancer , latent TB infection (a history of TB infection in the past based on testing), and young children below the age of 5 years.

    Purpose of this Study: 

    Is to compare how safe and effective 26 weeks of Delamanid (DLM), a medicine used to treat TB,  is versus 26 weeks of isoniazid (INH), a standard medicine to treat or prevent TB,  for preventing infection with TB (latent TB) or confirmed or probable active infection with TB among participantshigh risk HHC (see above for description).

    Requirements to Enter Study:

    The Index Case must be an adult (18 years and older) with pulmonary MDR-TB who has started MDR-TB treatment within the past 90 days, who has one or more household contacts and gives site staff permission to call and visit the household contacts.

    The Household contact must be a High-Risk Contact:

    • Children up to 5 years of age regardless of standard tests for TB known as the tuberculin skin test (TST) or the interferon gamma release assay (IGRA), a blood test for TB, or HIV status.
    • Adults, adolescents, and children ≥5 years of age who are TST-positive (defined as a skin test bump ≥5 mm in size) and/or IGRA test-positive and whose HIV status is negative, indeterminate, or unknown and who are not immunosuppressed from another condition besides HIV.
    • Adults, adolescents, and children ≥5 years of age who are HIV-infected or are immunosuppressed without HIV (defined as receiving anti-tumor necrosis factor (TNF) treatment, or in chronic renal failure receiving dialysis, or being solid organ or hematologic transplant recipients), regardless of TST/IGRA

    Treatment:

    Household contacts will be randomly assigned (like a flip of a coin) one of two groups:

    Group A will receive:

    DLM daily for adults, adolescents, and children, given for 26 weeks

    Group B will receive:

    • INH daily for adults, adolescents, and children, given for 26 weeks
    • Pyridoxine (vitamin B6) daily for adults, adolescents, and children, given for 26 weeks

    All high-risk HHCs in the same HH will receive the same randomized regimen.

    Duration of Study:

    All participants will be in this study for 96 weeks.

  • A5380: Glecaprevir/pibrentasvir Fixed-dose Combination Treatment for Acute Hepatitis C Virus Infection (PURGE-C)

    February 19, 2020 Alexis Sexton

    This is a study to treat participants, with or without HIV, who are found to have been recently infected with the Hepatitis C virus (HCV). This known as acute HCV.

    Purpose of this Study: People who are recently infected with HCV are often considered to have acute HCV. People with acute HCV have a good chance of being cured of the infection when they are treated with a combination of two drugs within the first 6 months of being infected. This study is being done to see if a shorter course of treatment will be effective if started early in the infection (Step 1). In case of failure with this shorter course of treatment, a longer and different treatment for HCV will be offered (Step 2).

    Requirements to Enter Study:

    • Age ≥18 years of age
    • With or without HIV. If living with HIV, on a stable treatment (antiretroviral regimen) or untreated due to lack of treatment per physician.
    • HIV RNA <50 and CD4 >100 cells/ mm3 (CD4 cells are a kind of white blood cell that are a measure of the immune system)
    • May not have Hepatitis B or prior Hepatitis C
    • Recently infected with HCV
    • Cannot be pregnant or breastfeeding
    • Must be willing to use birth control to prevent pregnancy
    • Must be willing to come to study visits
    • Must be able to swallow pills
    • May not have other known liver disease

    Study Drugs: Glecaprevir/pibrentasvir (G/P) Fixed-dose Combination (FDC-single tablet) three pills by mouth once a day for 4 weeks (Step 1). If this medicine does not work for you after the 4 weeks or you become infected again while on study, you will be asked to take the G/P with or without Ribavirin for a longer time, 8-16 weeks longer.

    Duration of Study: Up to 28 weeks on Step 1 and up to an additional 40 weeks if on Step 2.

  • A5381: Observational Cohort to Assess Therapeutic Efficacy and Emergence of HIV Drug Resistance Following Initiation of Tenofovir-Lamivudine-Dolutegravir (TLD) for First- or Second-Line ART

    February 11, 2020 Alexis Sexton

    This is a study for people who have HIV and qualify to switch to or receive Dolutegravir containing antiretroviral therapy (ART, group of medicine used to treat HIV). Taking TLD (combination pill of three medicines for HIV, tenofovir-lamivudine-dolutegravir) has shown to be better tolerated, work better against the virus known as virologic efficacy, have fewer drug-drug interactions, and have less frequent onset of HIV drug resistance than Efavirenz containing ART. In August 2017, a decision was made to start using TLD for first- and second-line ART in many places in the world. This study is designed to help us understand the risks and benefits of TLD roll-out in low- and middle-income countries that may not use viral load testing and HIV resistance testing (a way to measure if a drug will work against your HIV) to guide ART management.  Each participant will be assigned to one of four groups:

    • Group 1: Participants switching to TLD, after taking prior anti-HIV medication that contains a NNRTI drug (a group of medicines scientifically known as non-nucleoside reverse transcriptase inhibitors, such as Efavirenz or Nevirapine).
    • Group 2: Participants switching to TLD, after taking anti-HIV medication that contains a PI drug (a group of medicines scientifically known as protease inhibitors, such as Lopinavir or Atazanavir).
    • Group 3: Participants taking TLD and receiving medication for TB (tuberculosis) that includes the drug rifampicin. These participants must be starting one or both of these medications when they enter the study.
    • Group 4: Participants starting TLD who have not taken anti-HIV medication before.

    There will be 1350 participants enrolled in the study.

    Purpose of the study

    To better understand risks and benefits of Tenofovir-Lamivudine-Dolutegravir (TLD) roll out in programs done in low- and middle-income countries.

    Requirements to enter the study

    Persons with HIV  age 10 years or older

    Body weight at least 30 kg

    Starting or switching to Tenofovir-Lamivudine-Dolutegravir (TLD)

    Currently receiving or planning to receive care in a program supported by the United States President’s Emergency Plan for AIDs Relief (PEPFAR).

    Study Treatment

    There will be no treatment provided through the study.

    Duration

    Each participant will be followed for 36 months.

  • A5357: A Study of Long-Acting Cabotegravir Plus VRC01LS to Maintain Viral Suppression in HIV-1-Infected Adults

    January 2, 2020 Alexis Sexton

    This study is for people with HIV who have an undetectable viral load. The study will evaluate the safety and effectiveness of a combination of two medications. The first drug is called long-acting cabotegravir (CAB), which will be given orally at first and then as an injection every 4 weeks. The second drug is called VRC-HIVMAB080-00-AB (VRC01LS), which is a monoclonal antibody. A monoclonal antibody targets human proteins rather than attacking the virus directly. This drug will be given intravenously (directly into a vein, intravenous [or “IV”]) for about 15 to 30 minutes every 12 weeks.

    Why is this study being done?

    • The study will see if cabotegravir and VRC01LS work well when taken together to keep HIV levels low.
    • This study will also evaluate the safety of the drug combination.

    Who can join?

    People with HIV

    • Between the ages 18 and older
    • On stable anti-HIV medications for a minimum of 8 weeks
    • With a CD4+ cell count greater than or equal to 350
    • Having an undetectable HIV viral load (less than 40 copies)
    • With no current Hepatitis B or C infection
    • With no history of seizures or treatment for seizures within the past 2 years
    • With a susceptibility to VRC01LS based on assay done at screening

    What do I need to do in the study?

    Participants will be registered to three “steps”:

    Step 1: All participants will discontinue their current anti-HIV medications except for “nukes” and start oral CAB.

    Step 2: Participants may receive CAB long-acting drug by injection every 4 weeks, plus VRC01LS infusion by IV every 12 weeks.

    Step 3: Participants will be switched back to a standard-of-care oral HIV regimen.

    Duration of study: Participants will be on study for about 101 weeks.

    What treatments or drugs are involved with this study?

    The study provides oral and long-acting injectable cabotegravir and VRC01LS infusions.  Standard-of-care oral medications will be locally sourced.

  • A5375: Optimize LNG EC

    May 17, 2019 pendari

    Will determine if a higher dose of levonorgestrel Emergency Contraception (commonly called “Plan B” or the “Morning After Pill”) is needed to achieve high enough drug levels in girls and women who are taking anti-HIV medications that are known to decrease the effectiveness of this form of birth control.

    Treatment Category: Treatment Experienced

    Study Description
    This study will determine if a higher dose of levonorgestrel Emergency Contraception (LNG EC) (commonly called “Plan B” or the “Morning After Pill”) is needed to achieve high enough drug levels in girls and women who are taking medications that are known to decrease the effectiveness of this form of birth control.

    Efavirenz and rifampin, two medications commonly used to treat HIV and tuberculosis (TB), are known to lower the amount of LNG in the blood when LNG is used as a daily birth control pill. Dolutegravir, which does not lower the drug levels of LNG, will be the standard (control) group to which the other groups will be compared.

    Women who are receiving efavirenz will be randomized to take either the standard or double dose of LNG EC. Women on rifampin will take a double dose of LNG EC, while the control group on dolutegravir will take the standard LNG EC dose. Drug levels will be evaluated after taking one dose of LNG EC.

    Why is this study being done?

    • To see if participants who take a double dose of LNG EC and are on efavirenz or rifampin have similar drug levels as women who take the standard dose.
    • To see if a double dose of LNG EC is safe compared to the standard dose

    Who can join?

    • Females ≥16 years of age who have started menstruating
    • Not currently pregnant, within 6 weeks of delivery, or currently breastfeeding
    • Agree to use an approved non-hormonal birth control method during the study
    • Currently taking either efavirenz, dolutegravir, or rifampin
    • Have either HIV infection or an active TB infection

    What do I need to do in the study?
    All participants will receive one standard or double dose by mouth, depending on which medication they are currently receiving:

    Efavirenz: Randomized to either the standard dose (1.5 mg) or a double dose (3 mg) of LNG EC
    Rifampin: Double dose (3 mg) of LNG EC
    Dolutegravir: Standard dose (1.5 mg) of LNG EC

    At entry, participants will take their assigned standard or double dose of LNG EC and have their blood drawn nine times over about 9 hours. They will return to the clinic for blood level sampling after 24 and 48 hours, and will then be contacted by phone at weeks 1, 2, and 4.

    What treatments or drugs are involved with this study?
    The study treatment that will be provided through the study is levonorgestrel EC. Anti-HIV and TB medications will not be supplied through this study.

  • A5359: The LATITUDE Study

    May 17, 2019 pendari

    Investigating whether long-acting injectable medications will be more successful for people who are non-adherent to their HIV medications than oral regimens.

    Treatment Category:  Treatment Experienced

    Study Description

    This four-step study compares Long-Acting (LA) Injectable Antiretroviral Therapy (ART) to standard of care (SOC) oral ART in previously non-adherent individuals.

    Step 1 is the induction phase, and all participants receive study-provided SOC oral ART. Participants receive financial incentives for meeting study-specified goals.
    Step 2 is the randomization phase and participants are randomized 1:1 to receive LA ART or continue on SOC for 52 weeks.
    Step 3 is the crossover/continuation phase. Participants randomized to LA ART will continue that therapy, and eligible SOC participants will cross over to receive LA ART for 52 weeks.
    Step 4 is the observational phase that switches participants who received at least one LA ART injection and are no longer eligible for injections back to locally sourced oral SOC ART for 52 weeks.

    Study Status  

    Why is this study being done?

    • This study is investigating if LA injectable ART will be more successful for people who are non-adherent to their HIV medications than oral SOC regimens.
    • The main advantages of LA ART in this population include infrequent dosing and directly observed therapy. A challenge for participants is that, to be eligible to receive LA ART, they will need to attain virologic suppression through adherence to their SOC oral medications.
    • Financial incentives will be used during the first 20 weeks of the study to motivate participants to be adherent to an oral regimen until they are eligible to be randomized to either the LA ART arm or the SOC arm.

    Who can join?
    People living with HIV (PLWH) who are 18 years of age or older who

    • Have been prescribed anti-HIV medications (ART) for at least 6 months
    • Have an HIV viral load greater than 200 copies
    • Show evidence of non-adherence to their HIV medications by either:
      • Poor virologic response within the last 18 months (viral load greater than 200 copies at two time points at least 4 weeks apart)
      • Loss to clinical follow-up within the last 18 months, with ART non-adherence for at least 6 consecutive months
    • Have no active hepatitis B or C
    • Are willing to receive injections in the gluteus muscles (buttocks).

    What do I need to do in the study?

    Step 1: Induction (24 Weeks)
    All study participants will be prescribed an individualized oral study-provided ART regimen. In addition to financial compensation for attending study visits, participants will receive a financial incentive (bonus) if they attend their week 2 visit and achieve specific drops in their viral loads at weeks 4, 8, 12, 16, and 20. Participants whose viral load is <50 copies at week 20 will be eligible for randomization to Step 2 at their week 24 visit.

    Step 2: Randomization to LA ART Versus Oral SOC (52 Weeks)
    Participants will have a 50% chance of receiving either:

    LA ART Arm:
    Oral cabotegravir and oral rilpivirine daily for 4 weeks.
    –    During this 4-week oral phase, participants are monitored for side effects. Those who tolerate the oral medication will receive the LA form of cabotegravir and rilpivirine as intramuscular injections in the buttocks every 4 weeks for 48 weeks.

    OR

    SOC Arm:
    Continue taking SOC oral ART for 52 weeks.

    Step 3: LA ART Continuation/Crossover to LA ARV (52 weeks)
    LA ART Arm:
    Participants continue LA ART injections every 4 weeks for 52 weeks.

    SOC/Crossover Arm:
    Participants with an HIV RNA <50 copies at Step 2 week 48 or 52 are eligible to cross-over to LA ART.

    Step 4: Observation on SOC for Participants Who Received at Least One Dose of LA ART (52 weeks)
    This step is for participants that received at least one dose of LA ART and discontinued injections for any reason.

    Duration of Study:
    Steps 1-3 combined are a total of 128 weeks. Step 4 lasts 52 weeks.

    What treatments or drugs are involved with this study?
    The study provides oral and LA injectable cabotegravir and rilpivirine in Steps 1-3. Standard of care oral ART will need to be locally sourced.