• A5343: A Trial of the Safety, Tolerability, and Pharmacokinetics of Bedaquiline and Delamanid, Alone and in Combination, among Participants Taking Multidrug Treatment for Drug-Resistant Pulmonary Tuberculosis

    February 20, 2020 Alexis Sexton

    This is a randomized study, which means, by chance, you will be in one of three groups. You have an equal chance of being assigned to a group like flipping a coin. A5343 is an open label clinical trial, which means you will know which group you are in and what medications you will be taking.

    This study will compare three treatment arms for people who have pulmonary multidrug resistant tuberculosis (MDR-TB). Pulmonary MDR-TB is a form of tuberculosis (TB) in the lung that is resistant to two or more of the primary drugs used for the treatment of TB (isoniazid and rifampin).

    You will receive standard treatment for MDR-TB plus one or two new drugs for TB, called bedaquiline (BDQ) and delamanid (DLM). Throughout the study, you will be monitored to make sure that there are no safety concerns. Your heart will be monitored closely to make sure it is safe to give the drugs together.

    Purposes of the Study:

    This study looks at how the two new drugs fight MDR-TB when used alone with other TB drugs or used together. It looks at how the TB drugs work inside the body when you take them. It also looks at how safe and well tolerated these two drugs are in people.. Multiple times throughout the study, blood samples and an ECG, a test that measures the electrical activity in your heart, will be done to monitor the safety of the drugs.

    Requirements to Enter Study:

    Inclusion Criteria: To be in the study, you must:

    • Be age 18 or older
    • Have MDR-TB in your lungs and be on treatment less than 8 weeks
    • Not be pregnant or breastfeeding
    • Use an approved form of birth control for both men and women
    • For persons with HIV : CD4 count above 100 cells/mm3 (CD4 cells are a kind of white blood cell that are a measure of the immune system)
    • Taking treatment for MDR-TB before joining the study
    • Willing to stay in hospital for at least 2 months
    • Able to take pills by mouth
    • Consent in writing to be in the study

    Exclusion Criteria: You cannot be in the study if you:

    • Have MDR-TB that does not involve the lungs
    • Have received BDQ or DLM in the past
    • Have any allergies to the study drugs
    • Are actively drinking alcohol or using drugs
    • Have heart problems or other serious illness
    • Require or may require the use of certain drugs to treat HIV at the same time you are taking study drugs
    • Require or may require the use of certain drugs, including, but not limited to, clofazimine and moxifloxacin, from 48 hours prior to study entry through 4 weeks after stopping study drugs

    Study Treatment:

    The treatment arms are:

    • Arm 1: BDQ (comes as a tablet to take by mouth)
    • Arm 2: DLM (comes as a tablet to take by mouth)
    • Arm 3: Both BDQ and DLM (as above)

    The duration and doses will be explained by the study nurse or study doctor.

    Length of Study:

    24 weeks on study treatment, followed by 104 weeks follow-up, for a total length of 128 weeks

    Number of Participants:

    Up to 84 people will enroll in this study

  • 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.

  • 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.

  • A5361s: Pitavastatin to REduce Physical Function Impairment and FRailty in HIV (PREPARE)

    February 11, 2020 Alexis Sexton

    Aging with HIV may be associated with an earlier development of frailty (weakness) or disability, including difficulties in tests of strength or walking speed. Few treatments have been shown to prevent or slow these impairments in people with or without HIV. Some studies have suggested that the class of drugs called statins, such as pitavastatin, might be helpful in slowing frailty or disability. This might happen by decreasing fat within the muscle, or by decreasing inflammation markers in the blood. This study uses the REPRIEVE Trial (A5332) and the REPRIEVE Mechanistic Substudy (A5333s) to study the impact of pitavastatin on muscle.

    Requirements to enter the Study:

    • You must already be enrolled in REPRIEVE trial (A5332) and the REPRIEVE Mechanistic Substudy (A5333s)
    • Taking pitavastatin or placebo as part of REPRIEVE (A5332)
    • Willing to complete study procedures

    Study Procedures

    As part of A5361s, muscle strength and muscle function will be measured at yearly visits. Tests will include repeated chair rises, hand grip strength test, standing balance test and a 12 foot (4 meter) timed walk. Participants will also be asked questions about their physical activity.

    CT scans (done already in A5333s) will be looked at carefully for muscle size and fat amount and blood samples (collected in A5332) will be analyzed for changes in biomarkers. No additional CT scans or blood will be collected on A5361s.

    Duration of Study:

    Participants will be followed for 48 months from the date of enrollment into A5332. Based on their date of enrollment into A5332, participants may be followed between 24 to 48 months.

  • A5332: REPRIEVE Trial

    February 11, 2020 Alexis Sexton

    In this study, people between the ages of 40 and 75 with HIV will be randomized (like flipping a coin) to take the pill pitavastatin OR a placebo (non-active pill) to see if pitavastatin can help prevent heart disease and death in people who are taking HIV medication. You will not know if you are taking pitavastatin or placebo. The REPRIEVE trial will enroll about 7500 people from several countries.

    Purpose of this Study:

    HIV causes inflammation (irritation) inside the body that cannot be felt but can be measured. Inflammation may contribute to diseases such as heart disease that have become some of the leading causes of death in people with HIV. HIV medications can lower inflammation somewhat, however sometimes the levels of inflammation can remain higher compared to people who do not have HIV.

    Statins (name of the group of medicines that pitavastatin belongs to) are used to lower the levels of cholesterol and triglycerides (fat in the blood) that people make. Studies have shown that statins may have other benefits. For example, heart disease and the levels of inflammation can be lowered by statins.

    Pitavastatin is a statin that, along with a diet, has been approved by the US Food and Drug Administration for the treatment of high cholesterol. It also lowers triglyceride levels in the blood.

    The main purpose of this clinical trial is to see if pitavastatin can prevent heart disease and heart disease related deaths in people with HIV who are taking HIV medications.

    Requirements to Enter Study: The study coordinator will review all of the criteria necessary to be eligible for the study with you. Listed below are a few key points.

    • Persons with HIV who are between the ages of 40 and 75.
    • On antiretroviral therapy (ART, medicine to treat HIV) for at least 6 months prior to study entry.
    • CD4+ cell count >100. (CD4 cells are a kind of white blood cell that are a measure of the immune system)
    • Must not be pregnant or planning to become pregnant.
    • No history of cardiovascular disease (history of heart attack or stroke, etc.).
    • No history of cancer in the last year.
    • Not currently using a statin drug.

    Treatment: Participants will be randomized (like flipping a coin) to take either:

    • Pitavastatin 4 mg one pill daily with or without food or
    • Placebo for pitavastatin one pill daily with or without food

    Duration of Study: You will be in this study for about 36 to 96 months depending on when you enroll in the study. You will need to be seen in clinic for a screening visit, an entry visit, one month later, and then every 4 months.

  • A5324: A Randomized, Double-Blinded, Placebo-Controlled Trial Comparing Antiretroviral Intensification with Maraviroc and Dolutegravir with No Intensification or Intensification with Dolutegravir Alone for the Treatment of Cognitive Impairment in HIV 

    February 11, 2020 Alexis Sexton

    A5324 is a study for persons with HIV with undetectable HIV viral load who have mild neurocognitive impairment. Participants will be randomized (like a flip of a coin) to one of three study arms to add either placebo (sugar pill) for maraviroc (MVC) and placebo for dolutegravir (DTG) (Arm A), DTG active drug and placebo for MVC (Arm B), or MVC and DTG active drugs (Arm C) to their existing HIV treatment known as antiretroviral therapy (ART).

    Participants will be assessed with neurocognitive tests (test of how well your brain is working) and questionnaires about their daily life functions. There is an option to undergo lumbar punctures (spinal tap to test the fluid that surrounds the brain).

    Purpose of this Study:

    The main purpose of the study is to see if adding on MVC and/or DTG will improve neurocognitive performance and functioning in participants who have at least mild neurocognitive impairment and have an undetectable viral load. Safety and tolerability of MVC and DTG when added to a stable ART regimen and the effect of the study drugs on markers in the blood and spinal fluid will also be studied.

    Requirements to Enter Study:

    • Men or women with HIV at least 18 years of age
    • On current ART for at least 12 months
    • Undetectable HIV viral load (meaning <50 copies/mL on blood testing)
    • No more than one viral load test between 50 and 200 copies/mL (only one “blip”) in the past 6 months
    • At least mild HIV-associated neurocognitive impairment on neurocognitive tests done at screening
    • Able to complete the neuropsychological tests in English
    • No medical problem not related to HIV that may cause cognitive impairment
    • No current hepatitis C
    • No prior or current use of any integrase inhibitor or MVC
    • No active syphilis or treatment for syphilis

    Study Drugs

    Participants will be randomized (1:1:1 like a flip of a coin) to add one of the following regimens to their existing

    ART:

    Arm A: placebo for MVC and placebo for DTG

    Arm B: DTG and placebo for MVC

    Arm C: MVC and DTG

    Neuropsychological testing will be done at entry and every 24 weeks.

    A subset of participants will have optional lumbar punctures at entry and week 48.

    Duration of Study: 96 weeks

  • A5322: Long-Term Follow-up of Older HIV-infected Adults in the ACTG: Addressing Issues of Aging, HIV Infection and Inflammation (HAILO)

    February 11, 2020 Alexis Sexton

    You are being asked to take part in this research study because you are infected with HIV, the virus that causes AIDS, and were previously followed in the ALLRT (A5001) study and are 40 years of age or older. This study, A5322 (also known as the HAILO study), is a long-term follow-up study of persons who have HIV and received their first treatment for HIV known as antiretroviral medications, in certain clinical trials that were done by the AIDS Clinical Trials Group (ACTG).

    Purpose of this Study: 

    The purpose of this study is to help us learn about how HIV , aging and the immune system (how your body fights infection) all interact with each other to see how they relate to the development of illnesses such as kidney disease, cancer, and diabetes. This study will also see if treating people with HIV for these otherillnesses works as well as treating people without HIV for the same illness.

    Requirements to Enter Study:

    -PersonsParticipants 40 years of age and older who werebeing actively followed in the ALLRT (A5001), or recently completed follow-up in ALLRT, at the time of enrollment in A5322.

    -Received their first HIV treatment in an ACTG protocol and then enrolled intothe ALLRT parent protocol.

    -Eligible participantspartcipants must agree to be followed long-term to observe the aging process and for outcomes known as endpoints that are either clinical (you have a disease or health problem), virologic (meaning how your HIV responds to treatment) or  immunologic (meaning how your immune system reacts)while taking long-term treatment with HIV medicine.

    -Planned enrollment to include approximately 22% female participantssex participants (corresponding to the

    proportion of female sex participantsparticipants aged 40 years and older being followed in the ALLRT study).

    -Ability to commit to the long-term study requirements.

    Treatment: 

    Treatment for HIV must be arranged outside of the A5322 protocol. No treatment is given through the A5322 protocol.

    Special Testing:

    -As in ALLRT, participants will have the Neuroscreen at entry into A5322 and every 48 weeks thereafter.  This includes both Neurocognitive testing (i.e., digit symbol, HVLT-revised) and Neuropathy testing (i.e., tendon reflexes and vibratory sensation testing). -In addition, there will be a frailty assessment which will be performed for all participants enrolled in A5322. This consists of a hand grip assessment (measure of hand strength) followed by a 4-meter timed walk , along with several interviewer-administered questions on weight loss, physical activity and exhaustion.

    -Participation in A5322’s substudy (A5323s: Inflammation in the Functional Capacity: Trajectory of those Aging with HIV-Infection [FIT Substudy]) which is Optional. Participants enrolled in both A5322 and A5323s will complete the entire physical function battery which is detailed below:

    Grip Strength (A5322 and A5323s)

    4-meter Walk (A5322 and A5323s)

    Single Chair Rise (A5323s only)

    Repeated Chair Stands (A5323s only)

    Standing Balance Test (A5323s only)

    400-meter Walk (A5323s only)

    Duration of Study:

    Participants will be followed for 366 weeks (7 years).

  • A5368:Anti-PD-1 Antibody in HBV Infected on Suppressive Antiviral Therapy

    January 24, 2020 Alexis Sexton

    “Safety and Immunotherapeutic Activity of Cemiplimab in Participants with HBV on Suppressive Antiviral Therapy: A Phase I/II Ascending Multiple Dose Study”

    Brief Description: Scientists are looking at ways to cure Hepatitis B (HBV). This study will assess the safety and tolerability of cemiplimab administered in participants with HBV on suppressive antiviral therapy.

    Purpose of this Study: This study is trying to find out if cemiplimab is safe and well tolerated. Participants will receive multiple dose levels (0.3, 1.0, and 3.0 mg/kg) of cemiplimab administered as two infusions at weeks 6 and 12.

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

    • Have chronic HBV infection (defined as HBsAg positive) and under treatment for ≥12 months with tenofovir- or entecavir-containing therapy: tenofovir disoproxil fumarate (TDF), tenofovir alanfenamide (TAF), TDF/emtricitabine (FTC), TAF/FTC, or entecavir.
    • Be willing to continue HBV antiviral therapy throughout the study.
    • Have certain tests done.
    • Agree to use contraception/birth control methods.
    • Be 18 years old or older but less than 70 years.
    • Weight ≥40 kg.
    • Had evidence of limited or no evidence of fibrosis (F0-F2) by liver biopsy or noninvasive alternative method.
    • Be willing to sign the consent after discussion with the research staff.

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

    • Positive for the presence of Hepatitis C Virus.
    • Received investigational drug or device within 60 days prior to study entry.
    • Breastfeeding or pregnancy.
    • Known allergy/sensitivity or any hypersensitivity to components of study drug(s).
    • Active drug or alcohol use or dependence and other conditions that would interfere with adherence to study.
    • Acute or serious illness requiring systemic treatment and/or hospitalization within 35 days prior to study entry.
    • History of immunoglobulin IgG therapy or interferon (IFN) therapy within 12 months prior to study entry.
    • A male participant with a pregnant female partner.
    • Any vaccination within 30 days prior to entry.

    Treatment:

    • Multiple dose levels (0.3, 1.0 and 3.0 mg/kg) of cemiplimab administered as two infusions at weeks 6 and 12.

    Procedures:

    • Blood tests at clinic visits to check mainly hepatic and renal function.
    • Liver biopsy at study entry and at week 18 on study.
    • Leukapheresis for a group of participants.

    Duration of Study: Participants will be on study for up to 90 weeks (78 weeks following the last study drug infusion) with frequent safety evaluations.

  • 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.