Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of 2-Drug Therapy With Dolutegravir(DTG)/Rilpivirine(RPV) Fixed Dose Combination(FDC) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With NNRTI Mutation K103N

NCT05349838 | Completed Phase 3 Results DMC

• 2 other identifiers: NEAT 332017-004040-38
• Study Type: interventional
• Target: 140
• Locations: 6 countries
• Sites: 29

Brief Summary

HIV-1 infected subjects that experience virological failure while on non nucleoside reverse-transcriptase inhibitors (NNRTIs), including those with the K103N mutation, are usually switched to a boosted Protease Inhibitor (PI)-based regimen or other antiretroviral (ARV) combinations. The same is true for subjects who need to start antiretroviral therapy and have acquired virus that is already resistant to antiretrovirals. These "second line" combinations are often associated with numerous issues that can have a potential impact on the quality of life (QoL) of these patients. Therefore a simpler and better tolerated alternative second line treatment option would be a useful tool for the clinical management of these patients. The aim of this study is to assess the efficacy and tolerability of a dual combined therapy of Dolutegravir (DTG) 50 mg Once Daily (OD) + Rilpivirine (RPV) 25 mg OD in virologically suppressed participants with previous virological failure with NNRTIs and having the clinically significant mutation K103N. The secondary objective of the study is to assess whether a simplification of the treatment in terms of pill burden, long term metabolic toxicity and potential for drug interactions improves the QOL of the participants. The study will also evaluate DTG \& RPV concentrations in the blood plus changes in cell associated virus. In order to compare the first line treatment (boosted PI and/or other antiretroviral combinations) and the DTG+RPV combination, two thirds of study participants will be switched to DTG+RPV immediately and receive DTG+RPV for 96 weeks. The other third will be switched after 48 weeks of continuing on their first line treatment and receive DTG+RPV for 48 weeks. All participants will then be followed up for a further 30 days. Participants will be recruited from sites across Europe, and randomised onto either arm of the study. After randomisation, participants will attend approximately 10 visits over the course of two years.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• Number of Participants With and Without Virological Suppression

  Virological Suppression is defined as \<50 copies/ml HIV RNA

  48 weeks

Secondary Outcomes (29)

• Number of Participants With and Without Virological Suppression

  week 96

• Changes in Blood Cell Counts - Red Blood Cells

  Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96

• Changes in Blood Cell Counts - White Blood Cells

  Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96

• Changes in Blood Cell Counts - Platelets

  Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96

• Changes in Blood Cell Counts - Haemoglobin

  Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96

Other Outcomes (2)

• Changes in High Sensitivity C-Reactive Protein

  Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96

• Changes in CD4/CD8 Ratio

  Changed assessed from baseline to week 48, week 48 to week 96, baseline to week 96

Study Arms (2)

DTG/RPV FDC Regimen

EXPERIMENTAL

One combined Dolutegravir 50mg /Rilpivirine 25mg FDC tablet taken orally once daily

Drug: Dolutegravir & Rilpivirine 2 drug fixed dose combined therapy

Continued ART Regimen

ACTIVE COMPARATOR

Patients will continue the current boosted PI regimen (or other antiretroviral combination) for 48 weeks. Patients will then be switched to one combined Dolutegravir/Rilpivirine FDC tablet taken orally once daily for 48 weeks.

Drug: Dolutegravir & Rilpivirine 2 drug fixed dose combined therapy

Interventions

Dolutegravir & Rilpivirine 2 drug fixed dose combined therapy DRUG

Daily oral tablet

Also known as: Boosted protease inhibitors or other ARV regimen

Continued ART Regimen; DTG/RPV FDC Regimen

Eligibility Criteria

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

You may qualify if:

• Patient volunteers who meet all of the following criteria are eligible for this trial:
• Is male or female aged 18 years or over.
• Has documented HIV-1 infection
• Is capable of giving informed consent
• Is willing to comply with the protocol requirements
• Virologically suppressed (plasma HIV-RNA \<50 copies/mL for \>24 weeks) and on a stable regimen.
• Subjects are required to have a history of the K103N mutation (acquired or selected). Subjects who at any time have had the mutations 100I, 101E/P, 106A/M, 138K/G/Q, 181C/I/V, 188L, 190A/S/E/Q, 230L mutations are to be excluded. Other NNRTI region variants can be included. All PI and NRTI mutations are acceptable. Study sites may ask the coordinating centre for advice as required.
• Subjects must have never failed INSTI (2 x VL \>200 \>2 weeks apart) but current regimen can include Integrase Strand Transfer Inhibitor(INSTI).
• A female, may be eligible to enter and participate in the study if she:
• a. is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea without an alternative medical cause and ≥ 45 years of age) A high follicle stimulating hormone (FSH) level consistent with postmenopausal status may be used to confirm a post- menopausal state in women who are not using hormonal contraception) or hormonal replacement therapy at the discretion of the Principal Investigator. However, in the absence of 12 months of amenorrhea, a single FSH measurement alone is insufficient.
• OR physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
• OR is of child-bearing potential with a negative pregnancy test at Screening (\& baseline visit) and agrees to use one of the following methods of contraception to avoid pregnancy:
• True abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications (When this is in line with the preferred and usual lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception.
• Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year (not all IUDs meet this criterion, see Appendix 3 for an example listing of approved IUDs).
• Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject;

You may not qualify if:

• Patients meeting 1 or more of the following criteria cannot be selected:
• Infected with HIV-2
• Detectable HIV-1 RNA at screening (HIV-1 RNA measurement \>=50 c/mL).
• Subjects requiring regular dosing doing with H2 or PPI antacid medications or a history of achlorhidria or drug known to interact with RPV or DTG.
• Use of medications which are associated with Torsades de Pointes
• Corrected QT interval (QTc \[Bazett\]) \>450 milliseconds or QTc (Bazett) \>480 milliseconds for participants with bundle branch block. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB).
• Unstable health conditions (i.e. opportunistic infections, cancers, unstable liver disease etc).
• Any evidence of an active Centers for Disease Control and Prevention Category C disease. Exceptions include cutaneous Kaposi's sarcoma not requiring systemic therapy and historic CD4+ lymphocyte counts of \<200 cells/millimeter3.
• History or presence of allergy to the study drugs or their components or drugs of their class;
• Any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the subject's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participants. Subjects considered to pose a significant risk of suicide should be excluded.
• Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the subject unable to take oral medication;
• Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs. Specifically, co-administration with the following medicinal products is not allowed:
• dofetilide or pilsicainide;
• fampridine (also known as dalfampridine);
• carbamazepine, oxcarbazepine, phenobarbital, phenytoin;

Sponsors & Collaborators

• NEAT ID Foundation: lead
• ViiV Healthcare: collaborator

Study Sites (29)

Institute of Tropical Medecine

Antwerp, Belgium

Location

St Pierre University Hospital

Brussels, Belgium

Location

CHU Hotel Dieu

Nantes, France

Location

Hospital Saint Louis

Paris, France

Location

Pitié-salpêtrière Hospital

Paris, France

Location

University Bonn

Bonn, Germany

Location

University Essen

Essen, Germany

Location

Frankfurt University Hospital

Frankfurt, Germany

Location

ICH Study Center, Hamburg

Hamburg, Germany

Location

AAST delgi spedali civili di Brescia

Brescia, Italy

Location

ASST FBF SACCO- I Division of Infectious Diseases 1

Milan, Italy

Location

ASST FBF SACCO- I Division of Infectious Diseases 3

Milan, Italy

Location

I.R.C.C.S San Raffaele Hospital

Milan, Italy

Location

ASST GOM Niguarda Milano, Dep. Infectious Disease

Milan, Italy

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Herbo

Barcelona, Spain

Location

Infectious Diseases Unit Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital General Universitario de Elche

Elche, Spain

Location

Hospital Universitario La Paz, Madrid

Madrid, Spain

Location

Brighton & Sussex University NHS Trust

Brighton, United Kingdom

Location

North Bristol NHS Trust, Southmead Hospital

Bristol, United Kingdom

Location

Chelsea & Westminster Hospital

London, United Kingdom

Location

Kings College Hospital London

London, United Kingdom

Location

Mortimer Market Centre

London, United Kingdom

Location

Queen Elizabeth Hospital

London, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, United Kingdom

Location

St Marys Hospital

London, United Kingdom

Location

The Royal London Hospital

London, United Kingdom

Location

Related Publications (1)

• Moyle G, Assoumou L, de Castro N, Post FA, Curran A, Rusconi S, De Wit S, Stephan C, Raffi F, Johnson M, Masia M, Vera J, Jones B, Grove R, Fletcher C, Duffy A, Morris K, Pozniak A; NEAT ID Foundation and the WISARD study group. Switching to dolutegravir plus rilpivirine versus maintaining current antiretroviral therapy regimen in virologically suppressed people with HIV-1 and the Lys103Asn (K103N) mutation: 48-week results from a randomised, open-label pilot clinical trial. Lancet HIV. 2024 Mar;11(3):e156-e166. doi: 10.1016/S2352-3018(23)00292-8.

  PMID: 38417976 DERIVED

MeSH Terms

Interventions

dolutegravir; Psychotherapy, Multiple

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Research Organisation (KC) Ltd

WISARD@rokcservices.com

07376618244

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2019
• First Posted: April 27, 2022
• Study Start: November 5, 2018
• Primary Completion: November 15, 2021
• Study Completion: November 9, 2022
• Last Updated: December 24, 2024
• Results First Posted: December 24, 2024

Record last verified: 2024-11

Locations

DE (4); GB (9); FR (3); BE (2); ES (6); IT (5)