studies

ACTG A5364: A Phase I, Open-Label Study of the Safety and Ability of Broadly Neutralizing Antibodies 3BNC117-LS and 10-1074-LS in Combination to Durably Prevent Viral Relapse During a Monitored Analytical Treatment Interruption

Treatment Category: Experienced

Study Description
This is a Phase I, open-label, single-arm, multi-step study designed to evaluate the effects of the combination of long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS and 10-1074-LS in participants living with HIV who discontinue anti-HIV therapy (ART) during a monitored analytical treatment interruption (ATI), which is an extended period of time when not taking regular ART to control HIV.

Study Status: Open to Accrual

Why is this study being done?

• To see if it is safe to give people 10-1074-LS and 3BNC117-LS, and to see if these study drugs cause any side
• To evaluate the efficacy of the study drugs in preventing the return of HIV levels in the blood after interrupting ART.

Who can join?

• People with HIV between 18 and 70 years old.
• On stable ART with an undetectable viral load for at least 48 weeks prior to study entry.
• Body weight between 110 and 250 lbs.
• Participants who can become pregnant must agree to use two methods of contraception during the
• Be willing to temporarily stop taking ART medications.

What do I need to do in the study?

After screening, eligible participants will undergo leukapheresis (a procedure in which blood is collected from a vein in one arm, processed through an attached machine, and then returned through a vein in the opposite arm), and will be asked if they are interested in optional procedures (flexible sigmoidoscopy with rectal biopsy and/or lumbar puncture to collect spinal fluid). Three additional leukapheresis procedures will be done during the study.

At study entry, participants will receive an infusion of 3BNC117-LS and an infusion of 10-1074-LS, and will discontinue ART 2 days later.

Stopping ART is not recommended in the context of standard clinical care and poses some level of risk to the participant and sexual partner(s). However, for this research study, participants will be monitored closely while they are not taking ART. They will have to start taking ART again if blood tests show that it is necessary. The ATI can last up to 24 weeks of frequent visits to see if ART should be restarted.

Each participant will be followed for 72 weeks.

What treatments or drugs are involved with this study?

10-1074-LS and 3BNC117-LS are antibodies to HIV. Many antibodies are naturally made by the body and help fight diseases. 10-1074-LS and 3BNC117-LS are made in a laboratory. They are called “monoclonal antibodies,” which means that they are made up of many copies of one single antibody.

ACTG A5418: A Randomized, Placebo-Controlled, Double-Blinded Trial of the Safety and Efficacy of Tecovirimat for the Treatment of Human Monkeypox Virus Disease, Study of Tecovirimat for Human Monkeypox Virus (STOMP)

Treatment Category: Monkeypox

Study Description
A5418 (STOMP) is a study of tecovirimat (also known as TPOXX) for the treatment of human monkeypox virus (HMPXV) disease.

Study Status: Open

Why is this study being done?

• To see if tecovirimat is safe, and whether it helps treat monkeypox infection.

Who can join?

People with:

• Laboratory-confirmed or presumptive monkeypox infection
• Monkeypox illness of less than 14 days’ duration
• At least one active (not yet scabbed) skin lesion, mouth lesion, or proctitis (inflammation of the lining of the rectum) with or without visible ulcers

What do I need to do in the study?

Participants will be randomly assigned (like flipping a coin) in a 2:1 ratio to receive tecovirimat OR placebo for tecovirimat for 14 days.

People who are at higher risk for severe disease because of their age or their medical history will be assigned to receive open-label tecovirimat for 14 days.

All participants will be followed through a combination of in-person visits, specimen collection, virtual assessments, and self-reports and photographs of symptoms for about 2 months.

What treatments or drugs are involved with this study?

Tecovirimat is a drug that may help to treat infections caused by pox viruses. Tecovirimat is approved by the Food and Drug Administration (FDA) to treat smallpox in adults and children, but its use in this study is considered investigational.

Duration of Study

57 days

For more info: https://www.stomptpoxx.org/main

Brief Description:
This study will include 180 participants. Participants will have HIV and Cytomegalovirus (CMV). CMV is common virus that many people living with and without HIV have been exposed to. You do not need to know if you have CMV to be considered for study participation. About half of the study participants will be given study medication to be taken once daily for 48 weeks. The study medication will be letermovir, an FDA approved medication to prevent CMV. The other half of
participants will not receive any additional medication. The study will last about 1 year and 2 months.
Purpose of this Study:
To learn whether people living with well controlled HIV and symptom free CMV can reduce inflammation by taking a drug approved by the FDA to prevent CMV disease.
To Enter the Study, the following must be true about you:

• HIV positive, ≥40 years of age
• On continuous anti-HIV medications for at least 48 months with no interruptions >7 days
• At least 48 months of undetectable viral loads, although a one-time, low-level viral load is OK
• Have not made significant change in HIV medication in the past 12 weeks, or plan to make changes during study participation
• No heart arrythmias/ irregular heart beats
• No active Hepatitis B or hepatitis C within 24 weeks
• Not currently using any of the following HIV medications: efavirenz, nevirapine, etravirine, lopinavir/ritonavir, or once a day dosing of raltegravir (twice a day dosing is OK)
• While people with any CD4 count are eligible, the study is particularly interested in recruiting people with low CD4 counts (i.e., <350 cells/mm3)
• While people of all gender identities are eligible, the study is particularly interested in recruiting cis-gender women and transgender women receiving gender-affirming hormones

Treatment:
There will be treatment provided in this study. Letermovir is a pill given by mouth once a day that is FDA-approved to prevent CMV disease. There are two study treatment groups.
You will have a 50/50 chance of going into one of the two groups. Participants in one group will get letermovir and participants in the other group will not get any additional medications.

Brief Background and Description: Since the early days of the HIV epidemic cytomegalovirus (CMV) has been one of the most common and devastating opportunistic infections (OIs) experienced by people with HIV. CMV is a common virus that usually causes few, mild, or no symptoms and typically remains in the body for life; in people with weakened immune systems, however, CMV can cause more serious symptoms affecting the eyes, lungs, liver, esophagus, stomach, and intestines ). HIV and CMV can work together against our bodies’ defenses, making transmission of each virus easier. We would like to change this.

In this study, you will be randomized to one of the study treatment arms. You will receive either Triplex^® study vaccine or placebo by injection into the muscle of your shoulder 2 times; once when you enter the study and again about 4 weeks later.

Purpose of this Study: The purpose of this study is to see if an investigational vaccine for CMV (called Triplex®) is safe when given to people with both HIV and CMV. This study will also collect information on the effectiveness of Triplex® to reduce inflammation and immune activation markers compared to a placebo. This will be the first time that this type of information will be collected. You should be aware that the current standard of care for individuals with both HIV and CMV includes effective treatment for HIV but does not include treatment of CMV with either medication or vaccination – unless there is evidence that the CMV is causing or contributing to illness.

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

• Living with HIV-1 and with cytomegalovirus (CMV).
• Be between 18 and 65 years old.
• On an anti-HIV medications that are controlling your HIV for at least the past year.
• Agree to use contraception/birth control methods if capable of becoming pregnant or impregnating someone else.

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

• Use of anti-CMV drugs within the past 2 weeks.
• Currently have hepatitis B or hepatitis C
• Currently have a sexually transmitted infection (such as, gonorrhea, syphilis, or chlamydia)
• History of CMV disease and symptoms within the past 12 months.
• Receipt of any vaccine (including for COVID-19) within the previous 4 weeks.
• Recent serious illness or condition requiring hospitalization.
• Breastfeeding or pregnant.
• Historic or current evidence of resistance to the study medication or other medications in its class.

Talk to your study staff for a complete list of inclusion/exclusion criteria. 

Intervention:

When you enter this study, you will be randomized (assigned by chance, as if by roll of dice) to one of two study groups. You will have double the chance of receiving Triplex^® versus the placebo. You must continue to take your anti-HIV drugs throughout the study.

Procedures:

• Blood and urine tests at scheduled clinic visits for safety evaluations and other research testing.
• Questionnaires asking for information on adherence to ART and use of other drugs.
• For 4 weeks following each study injection you will complete a daily study diary (which is also known as a study vaccination report card); you will need to take and record your body temperature for the first 5 days each time.
• At several of the clinic visits, saliva, rectal swabs, and/or genital fluid (semen or vaginal swab) will be collected.

Duration of Study: About 2 years (96 weeks). In the first month of the study, you will have 2 study visits and 2 telephone contacts with clinic staff. After that, you will have 5 more visits over the next 16 months. After you have been on the study for about 2 years (about 4 months after your last study visit), your participation will end with a phone call from the clinic staff.

Right now there is no medicine proven to treat COVID-19 in people who are not sick enough to be hospitalized. Researchers will be testing different investigational medicines that they believe are most likely to help people with COVID-19.

They want to see if these investigational medicines:

• Are safe for those who need them
• Can help people get better faster
• Can get rid of the virus
• Can help keep oxygen levels up
• Can keep people from getting sicker
• Can prevent people from having to go to the hospital

The whole study lasts about 6 months (24 weeks).

During the study you would have in-person visits with tests to check on your health. Most of these visits happen during the first month of the study.

You would also have phone calls or videos chats with the researcher from your home.

The study team will give you a diary to keep track of your temperature each evening and any symptoms you have. You’ll be asked to fill out this diary for the first 28 days.

If the study is right for you, you will have your first visit, or entry visit, to meet with a researcher for tests and to be placed in a treatment group.

Each study medicine will be compared to a placebo. A placebo looks like the real drug but doesn’t have any actual medicine in it. This gives researchers something to compare the study medicine to. You would not know if you are receiving the study medicine or placebo until the end of the study. If a standard treatment for COVID-19 is found during the study, that treatment will be used instead of placebo. Different medicines may be tested during the study at the same time. One type of investigational medicine you might receive is called a monoclonal antibody. Antibodies are naturally made by your body to help fight disease. Monoclonal antibodies are made in the lab and help your body attack invaders, such as viruses, to keep them from entering your cells. Once you are placed in a treatment group, you will receive more information on that investigational medicine being tested, including any possible side effects.

To learn more about this study click here.

Study Description
A5362 is a study for people with pulmonary tuberculosis (TB) without evidence of resistance to the TB drugs isoniazid (INH) or rifampin (RIF). Participants will be enrolled in one of three treatment groups. Duration of treatment will vary depending on which treatment group the participant is enrolled, but all participants will be in the study for 65 weeks.

Study Status:    Open to Accrual

Why is this study being done?

• To determine if taking a shorter 3-month regimen of a new combination of TB drugs is better than taking a 6-month regimen that is standard of care for the treatment of TB.
• To look at the tolerability of the study drugs, the effect the drugs have on the electrical activity of the heart, and will measure the level of these drugs in blood.

Who can join?

People who:

• Are 18 years of age or older
• Have pulmonary TB with or without history of prior treatment, and without known resistance of INH or RIF
• Have a normal chest X-ray at screening
• For participants living with HIV: CD4 cell count ≥100 and taking or planning to take anti-HIV therapy
• Not more than 5 days of treatment directed against active TB for the current TB episode

What do I need to do in the study?

For this three-arm study, participants will receive treatment in either:

Arm 1

Rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) high dose for 2 weeks; then PHZE + CFZ standard dose for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ standard dose 5 weeks, for a total of 13 weeks of study treatment.

Arm 2 (Standard of Care)

Rifampin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampin/isoniazid (RH) for 18 weeks, for a total of 26 weeks of study treatment.

Arm C

PHZE + CFZ standard dose for 4 weeks; switch to standard of care, completing RHZE for 4 weeks; then RH for 18 weeks.

All participants will have blood samples taken to measure the amount of anti-TB drugs in the body, and pictures taken to look for changes in skin color. All participants will undergo routine safety monitoring.  Participants will be followed in the study for 65 weeks.

What treatments or drugs are involved with this study?

Study TB medications are provided by the study. Antiretroviral medications are not provided by the study.