UK Community Advisory Board (UK-CAB)

CAB 86: Doravirine/Islatravir studies; MSD meeting, Breast feeding guidelines, Positive voices survey

Date: 1 March 2024
Venue: Room MAL G16, Birbkeck (main building) Malet Street, London WCIE 7HX
Register to attend the meeting here: https://forms.gle/NhFuJ3UQFM37vsRR9

Programme:

09.30-09.45 Arrival, tea and refreshments, expenses
09:45- 10.00 Welcome and introductions – Nicoletta Policek, UK-CAB chair

UK-CAB updates – UK-CAB SG member

10:00-11.00 Doravirine/Islatravir studies – Dr Laura Waters, Mortimer Market Centre
11:00-11.40 Company meeting: MSD
Diversity in clinical trial recruitment
11.40-11.45 BREAK
11.45-12.30 Breastfeeding guidelines – Shema Tariq, UCL -TBC
12:30-14.00 LUNCH
14:00-15:00 Uganda LGBT activists: Shawn Mugisha and Stella Nyanzi
15:00 – 15:30 Member updates/discussion
15.30-15.45 BREAK
15.45-16.30 Meeting reflection
16.30 – 17:00 Any other business, next meeting

Meeting close

Presentations from this meeting

MSD pre-meeting
Doravirine/Islatravir studies
Company meeting – MSD: confidential slides available to members only on request
BHIVA Breastfeeding guidelines
Positive voices survey

Background reading

DOR/ISL in heavily treatment-experienced participants

Full title
A Phase 3, Randomized, Clinical Study in HIV-1-Infected Heavily Treatment-Experienced Participants Evaluating the Antiretroviral Activity of Blinded Islatravir (ISL), Doravirine (DOR), and Doravirine/Islatravir (DOR/ISL), Each Compared to Placebo, and the Antiretroviral Activity, Safety, and Tolerability of Open-Label DOR/ISL.

Islatravir is in Phase 3 development for HIV treatment. It is being developed as part of a fixed-dose combination containing doravirine and islatravir (DOR/ISL) and as a stand-alone agent. Islatravir is also being studied for HIV prevention; however, the development of once-monthly oral islatravir for HIV prevention is being discontinued.

Research summary

Heavily treatment-experienced (HTE) individuals are a small but important population of patients with HIV-1. These individuals have exhausted all or nearly all antiretroviral options for constructing a viable HIV treatment regimen primarily because of extensive multidrug resistance but also because of drug intolerance, lack of access to key drugs, or unacceptability to the participant. There is consequently an unmet medical need in this population for better treatment options. Preliminary data suggest Islatravir (ISL) may be useful in this population.

Islatravir is the first of a new class of antiretroviral agents, and Doravirine (DOR) is an European Medicines Agency (EMA) and Food and Drug Administration (FDA) approved antiretroviral drug, both of which work by blocking steps in the HIV-1 virus replication, thus reducing the levels of the virus in the patient and consequently allowing the immune system to repair itself and prevent further damage.

Doravirine/Islatravir (DOR/ISL) combination drug has the potential to be an ideal agent for the treatment of HIV-1 infection in the HTE population due to its potent antiretroviral activity by multiple mechanisms of action, lack of food requirements, and favourable safety and Drug-drug Interaction (DDI) profiles observed to date.

This 2-part, multicentre phase 3 study will recruit approximately 100 male and female participants over the age of 12. This study will assess the anti-retroviral activity of DOR/ISL compared to placebo, and the safety and tolerability of DOR/ISL. For part 1, participants will be assigned randomly into 1:2:1:1 to one of 4 treatment arms for day 1 to day 7 of the study. For part 2, all participants will receive DOR/ISL plus optimised background therapy from day 8 to week 49.

The study is funded by Merck Sharp & Dohme Limited and will take place at 8 study centres in the UK.
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DOR/ISL 100 mg/0.25 mg QD Blinded Switch
Full title
A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

Research summary
As treatment regimens have improved, HIV-1 infection has become a chronic, manageable condition. The current standard of care includes 3-drug regimens. However, there is evidence 2-drug regimens can be as effective whilst improving tolerability and quality of life, which in turn may support patient adherence to treatment and continued suppression of disease.

This trial is testing Doravirine (DOR)/ Islatravir (ISL), also called MK-8591A, in people with HIV-1. DOR/ISL is a combination of 2 drugs: DOR (approved by some health authorities to treat HIV-1) and ISL(an experimental drug not approved to treat HIV-1). DOR/ISL has the potential to be an effective 2-drug regimen due to its effects against HIV-1, multiple mechanisms of action and lack of food requirements. Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) is a standard treatment for HIV-1.

Around 501 male and female participants will be enrolled in this trial. Participants must be 18 years of age or older and have been getting BIC/FTC/TAF to control their HIV-1 for at least 3 months.

After a screening phase of up to 45 days, eligible participants will be randomised in a 2:1 ratio into 1 of 2 treatment groups:
• Group 1: DOR/ISL and a placebo
• Group 2: BIC/FTC/TAF and placebo

Participants will receive treatment for 96 weeks (2 years). DOR/ISL, BIC/FTC/TAF, and the placebo are tablets taken once a day.

After the participants stop getting the trial drugs, they will enter the follow-up phase. Participants may have additional follow-up visits depending on blood test results, if the participant continues treatment during pregnancy or if they stop taking trial drugs early.

Participants who complete the last visit may be given an opportunity to receive open-label DOR/ISL until it is commercially available, provided the development of DOR/ISL continues.

The trial is sponsored by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (MSD).

 

UK-CAB funding

The administration of the UK-CAB are covered from the core budget of  i-Base. Some costs for UK-CAB meetings are covered by support from pharmaceutical companies (see details below).

Funding by pharmaceutical companies

We ask pharmaceutical companies that have current HIV drugs to help fund the UK-CAB and the quarterly training meetings.

The funding covers the project administration, travel and accommodation for members attending from out of London, as well as the cost of catering for the four meetings. This funding helps support the UK-CAB as a national project. A list of supporting companies since the UK-CAB was established in 2002 and from the most recent two years is included below. [3]

The UK-CAB membership and the Steering Group decide the content and agendas for the programme of meetings. When the UK-CAB meets with pharmaceutical companies about their current products and future research, the decisions for which companies to invite and the agenda for these meetings is made by the UK-CAB.

We similarly ask independent researchers to actively involve the UK-CAB in planning studies and ongoing research. We ask that community involvement in research be included in the budget of grant proposals so that some of the UK-CAB work can be supported in this way by independent research.

Notes

  1. Directors and employees of pharmaceutical companies involved in research into HIV treatment and diagnostics, or employees of agencies providing PR, marketing and other professional services for these companies may not join the UK-CAB. We work closely with industry, but the UK-CAB is a community-based network, and it is important to respect this boundary.
  2. UK-CAB cannot provide any funding for people travelling from outside England, Wales, Scotland, Northern Ireland, Isle of Man or the Channel Islands.
  3. Since 2002, the UK-CAB has received support towards meeting costs from the following pharmaceutical companies: Abbott Laboratories, AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb (BMS), Gilead Sciences, GlaxoSmithKline (GSK), Janssen-Cilag, Koronis, Merck Sharp and Dohme (MSD), Roche Laboratories, Theratechnologies, Tibotec, Pfizer, ViiV Healthcare.
    Since April 2012, the UK-CAB has been supported by Abbott Laboratories, AbbVie, Bristol-Myers Squibb (BMS), Gilead Sciences, Janssen-Cilag, Merck Sharp and Dohme (MSD) and ViiV Healthcare.
    This funding is unconnected to the programme and content of meetings.