Cabotegravir and Rilpivirine

Associated long-acting platforms

Aqueous drug particle suspension

Administration route

Oral, Subcutaneous, Intramuscular

Therapeutic area(s)

Use case(s)

Use of drug

Drug information

Delivery device(s)

No delivery device

Scale-up prospects

Compounds are commercially manufactured.

Tentative equipment list for manufacturing

Conventional wet-bead milling apparatus (e.g. Netzsch ball mill), depyrogenated glass vials, high pressure homogenizer.

Manufacturing

Cabotegravir and Rilpivirine are formulated into a wet-mill suspension of approximately 200mg/ml and 300mg/ml respectively, due to their low aqueous solubility. This formulation results in the creation of nanocrystal drug particles which are amenable for intramuscular gluteal depot injection. The manufacturing process for RPV is considered to be non-standard due to the inclusion of an aseptic processing step. RPV is light-sensitive, and exposure to light can induce conversion into a Z-isomer form which can affect pharmacokinetic data and activity.

Specific analytical instrument required for characterization of formulation

PANalytical X’Pert PRO diffractometer equipped with a theta/theta coupled goniometer (or equivalent x-ray powder diffractor), Mettler TGA/DSC 1 instrument for thermal analysis, Laser diffractor (determine particle size), FT-IR UHPLC (chemical identification), UHPLC (chromatographic purity), paddle apparatus & UPLC/UV (determine in-vitro drug release for QC / dissolution testing).

POLAR

Identifier

NCT03639311

Link

https://clinicaltrials.gov/study/NCT03639311

Phase

Phase II

Status

Completed

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Assess the antiviral activity and safety of CAB LA plus RPV LA, administered Q2M, in approximately 100 adult HIV-1 infected, antiretroviral therapy (ART) experienced participants.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2018-08-20

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2019-12-11

Actual Completion Date
2023-01-30

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Participants will rollover from the NCT01641809 (LATTE) study, who have completed minimum duration of Week 312 and with demonstrated HIV-1 ribonucleic acid (RNA) suppression (less than [<]50 copies (c) per milliliter [mL]), while receiving a two-drug regimen consisting of once-daily oral CAB at 30 milligram (mg) plus RPV at 25 mg. The participants will be offered the option to switch to the LA, intramuscular injections of CAB LA plus RPV LA, Q2M or the oral fixed dose combination (FDC) of dolutegravir (DTG) plus RPV, for the continued maintenance of HIV-1 RNA suppression, known as the Maintenance Phase (From Day 1 to Commercial Approval).

Health status

Study type

Interventional (clinical trial)

Enrollment

97

Allocation

Non-randomized

Intervention model

Parallel Assignment

Intervention model description

This is an Intervention Model, with parallel assignment, where the primary purpose of the study is, treatment, with 2 arms and no masking.

Masking

Open label

Masking description

This is an open-label study, thus no masking.

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

CUSTOMIZE

Identifier

NCT04001803

Link

https://clinicaltrials.gov/study/NCT04001803

Phase

Phase III

Status

Completed

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Identify and Evaluate Strategies for Successful Implementation of the Cabotegravir + Rilpivirine Long-acting Injectable Regimen in the US.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-07-08

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2020-10-05

Actual Completion Date
2022-03-18

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Not provided

Health status

Study type

Interventional (clinical trial)

Enrollment

115

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

CR109089

Identifier

NCT05112939

Link

https://clinicaltrials.gov/study/NCT05112939

Phase

Phase I

Status

Active, not recruiting

Sponsor

Janssen Research & Development, LLC

More details

Not provided

Purpose

Characterize the single dose pharmacokinetics and evaluate the safety and tolerability of subcutaneous administration of RPV LA in combination with CAB LA in different conditions in healthy adults.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2021-11-16

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
2024-05-23

Estimated Completion Date
2024-05-23

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Participant must be healthy on the basis of physical examination, clinical laboratory tests, medical history, vital signs, and 12-lead electrocardiogram (ECG).

Health status

Not provided

Study type

Interventional (clinical trial)

Enrollment

126

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Single blind masking

Masking description

Single (Participant)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

ATLAS-2M

Identifier

NCT03299049

Link

https://clinicaltrials.gov/study/NCT03299049

Phase

Phase III

Status

Active, not recruiting

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Evaluating the Efficacy, Safety, and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine in HIV-1-infected Adults Who Are Virologically Suppressed.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2017-10-27

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
2026-12-31

Actual Primary Completion Date
2019-06-06

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Not provided

Health status

Study type

Interventional (clinical trial)

Enrollment

1049

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Two groups of subjects will be randomized to receive CAB LA + RPV LA Q4W, or CAB LA + RPV LA Q8W regimen.

Masking

Open label

Masking description

This will be an open-label study and therefore no blinding is required.

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

SOLAR

Identifier

NCT04542070

Link

https://clinicaltrials.gov/study/NCT04542070

Phase

Phase III

Status

Completed

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Assess the antiviral activity and safety of a two-drug regimen of CAB LA + RPV LA compared with maintenance of BIK. BIKTARVY is a registered trademark of Gilead Sciences.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2020-11-09

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2022-07-13

Actual Completion Date
2023-04-17

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Not provided

Health status

Study type

Interventional (clinical trial)

Enrollment

687

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

ATLAS

Identifier

NCT02951052

Link

https://clinicaltrials.gov/study/NCT02951052

Phase

Phase III

Status

Active, not recruiting

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Establish if HIV-1 infected adult subjects with current viral suppression on a regimen with 2 NRTIs plus a third agent, remain suppressed upon switching to a 2 drug intramuscular regime of CAB/RPV-LA.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2016-10-28

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
2026-12-31

Actual Primary Completion Date
2018-05-29

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Must be on uninterrupted current ARV regimen (either the initial or second ARV regimen) for at least 6 months prior to Screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for treatment failure (HIV-1 RNA ≥400 c/mL).

Health status

Study type

Interventional (clinical trial)

Enrollment

618

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

FLAIR

Identifier

NCT02938520

Link

https://clinicaltrials.gov/study/NCT02938520

Phase

Phase III

Status

Active, not recruiting

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Establish if HIV-1 infected adult participants whose virus is virologically suppressed on an INI STR will remain suppressed after switching to a two drug LA regimen of CAB and RPV.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2016-10-27

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
2026-12-31

Actual Primary Completion Date
2018-08-30

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Antiretroviral-naive (<=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection). Any previous exposure to an HIV integrase inhibitor or non-nucleoside reverse transcriptase inhibitor will be exclusionary.

Health status

Study type

Interventional (clinical trial)

Enrollment

631

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

CARISEL

Identifier

NCT04399551

Link

https://clinicaltrials.gov/study/NCT04399551

Phase

Phase III

Status

Completed

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Evaluating Implementation Strategies for Cabotegravir (CAB)+ Rilpivirine (RPV) Long-acting (LA) Injectables for Human Immunodeficiency Virus (HIV)-1 Treatment in European Countries

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2020-09-28

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2022-03-07

Actual Completion Date
2023-03-13

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

HIV-1 infected and must be suppressed on a guideline recommended active Highly active antiretroviral therapy (HAART) regimen for at least 6 months prior to screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must not have been done for virologic failure (on treatment HIV-1 RNA more than or equal to [>=]200 c/mL).

Health status

Study type

Interventional (clinical trial)

Enrollment

437

Allocation

Non-randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

This is an open-label study hence no blinding is required.

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

LATA

Identifier

NCT05154747

Link

https://clinicaltrials.gov/study/NCT05154747

Phase

Phase III

Status

Recruiting

Sponsor

University College, London

More details

Not provided

Purpose

Comparing the efficacy of long-acting injectable CAB+RPV administered every two months in comparison to daily oral HIV medications in young people.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2023-06-22

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
2025-03-01

Estimated Completion Date
2025-03-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Children
• Adolescents
• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Study participants are individuals with HIV-1 infection aged 12-19 years in Sub-Saharan Africa. Participants with known HIV-2 infection are excluded.

Health status

Study type

Interventional (clinical trial)

Enrollment

460

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

IMPALA

Identifier

NCT05546242

Link

https://clinicaltrials.gov/study/NCT05546242

Phase

Phase III

Status

Recruiting

Sponsor

MRC/UVRI and LSHTM Uganda Research Unit

More details

Not provided

Purpose

Evaluating the Effectiveness of Switching to Two-monthly Long-acting Injectable CAB and RPV From First-line Oral Antiretroviral Therapy in HIV-1 Positive Virologically Suppressed Adults in SSA.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2022-12-08

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
2024-11-01

Estimated Completion Date
2025-11-01

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Participants must have a history of sub-optimal ART adherence or engagement in care based on one or more of the following criteria: 1. Documented detectable HIV-1 VL (>1000 c/mL) on all-oral ART (EFV/NVP or DTG-based) in the prior 2 years despite being ART-experienced for ≥3 months. 2. History of being lost to follow-up from care (>4 weeks elapsed since a missed scheduled clinic appointment or refill in the prior 2 years). 3. Failed to link to HIV care despite ≥3 months elapsed since HIV diagnosis.

Health status

Study type

Interventional (clinical trial)

Enrollment

540

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Parallel open-label phase 3b study. Participants will be randomised to continuing current therapy or switching to injectable therapy.

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

LATITUDE

Identifier

NCT03635788

Link

https://clinicaltrials.gov/study/NCT03635788

Phase

Phase III

Status

Recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

Not provided

Purpose

Compare the efficacy, safety, and durability of two different strategies to treat participants with a history of sub-optimal adherence and control of their HIV infection.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-03-28

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
2025-06-30

Estimated Completion Date
2026-12-31

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Evidence of non-adherence to ART according to at least one of the following criteria: 1. Poor virologic response within 18 months prior to study entry (defined as less than 1 log10 decrease in HIV-1 RNA or HIV-1 RNA greater than 200 copies/mL at two time points at least 4 weeks apart) in individuals who have been prescribed ART for at least 6 consecutive months. 2. Lost to clinical follow-up within 18 months prior to study entry with ART non-adherence for greater than or equal to 6 consecutive months.

Health status

Study type

Interventional (clinical trial)

Enrollment

350

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

LATTE-2

Identifier

NCT02120352

Link

https://clinicaltrials.gov/study/NCT02120352

Phase

Phase II

Status

Completed

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Evaluate the antiviral activity, tolerability, and safety of IM dosing regimens of GSK744 LA plus TMC278 LA, relative to GSK744 plus ABC/3TC given orally once daily, in ARV naïve HIV-1 patients.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2014-04-28

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2015-08-13

Actual Completion Date
2023-04-20

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Participants must be ART-naïve defined as having no more than 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection.

Health status

Study type

Interventional (clinical trial)

Enrollment

309

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

NCT04371380

Identifier

NCT04371380

Link

https://clinicaltrials.gov/study/NCT04371380

Phase

Phase I

Status

Completed

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Evaluate pharmacokinetics, tolerability, and safety of Cabotegravir long acting plus Rilpivirine long acting administered concomitantly as two separate IM injections in the Vastus Lateralis muscles.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2020-09-16

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2021-12-26

Actual Completion Date
2021-12-26

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
Yes

Comments about the studied populations

Participants aged 18 to 50 who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.

Health status

Study type

Interventional (clinical trial)

Enrollment

15

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Eligible participants will receive orally, tablets of cabotegravir plus rilpivirine for 28 days. There will be 10 to 14 days wash out period followed by an IM injection of cabotegravir long-acting plus rilpivirine long-acting.

Masking

Open label

Masking description

This is an open label study.

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

LAI115428

Identifier

NCT01593046

Link

https://clinicaltrials.gov/study/NCT01593046

Phase

Phase I

Status

Completed

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Investigate the Safety, Tolerability and Pharmacokinetics of Repeat Dose Administration of Long-Acting GSK1265744 and Long-Acting TMC278 Intramuscular and Subcutaneous Injections.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2012-05-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
Not provided

Actual Primary Completion Date
2013-11-01

Actual Completion Date
2013-11-01

Studied populations

Age Cohort

• Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
Unspecified

Accepts healthy individuals
Yes

Comments about the studied populations

Not provided

Health status

Study type

Interventional (clinical trial)

Enrollment

43

Allocation

Randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Unspecified

Key results

CAPRI

Identifier

NCT05601128

Link

https://clinicaltrials.gov/study/NCT05601128

Phase

Phase III

Status

Recruiting

Sponsor

Allegheny Singer Research Institute

More details

Not provided

Purpose

Evaluate the efficacy and safety of CABENUVA (Long-acting Cabotegravir Plus Long-acting Rilpivirine) in patients with HIV infection and severe renal impairment.

Interventions

Countries

Not provided

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2023-01-01

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
2024-12-31

Estimated Completion Date
2025-12-31

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Participants are positive for HIV infection and severe renal impairment with or without hemodialysis.

Health status

Study type

Interventional (clinical trial)

Enrollment

12

Allocation

Not provided

Intervention model

Single group assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

MOCHA

Identifier

NCT03497676

Link

https://clinicaltrials.gov/study/NCT03497676

Phase

Phase I/II

Status

Recruiting

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

More details

Not provided

Purpose

Evaluate the safety, acceptability, tolerability, and pharmacokinetics of oral and long-acting injectable CAB and RPV in virologically suppressed HIV-infected children and adolescents.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2019-03-19

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
Not provided

Estimated Completion Date
2025-06-17

Actual Primary Completion Date
2023-02-18

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Children
• Adolescents

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Not provided

Health status

Study type

Interventional (clinical trial)

Enrollment

155

Allocation

Non-randomized

Intervention model

Sequential assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

VOLITION

Identifier

NCT05917509

Link

https://clinicaltrials.gov/study/NCT05917509

Phase

Phase III

Status

Recruiting

Sponsor

ViiV Healthcare

More details

Not provided

Purpose

Evaluate the efficacy, safety, implementation effectiveness, and patient-reported outcomes of once-daily oral DTG/3TC followed by an optional participant-determined switch to CAB/RPV-LA.

Interventions

Countries

Sites / Institutions

Not provided

Trials dates

Anticipated Start Date
Not provided

Actual Start Date
2023-07-06

Anticipated Date of Last Follow-up
Not provided

Estimated Primary Completion Date
2025-09-29

Estimated Completion Date
2026-01-30

Actual Primary Completion Date
Not provided

Actual Completion Date
Not provided

Studied populations

Age Cohort

• Adults
• Older Adults

Genders

• All

Accepts pregnant individuals
No

Accepts lactating individuals
No

Accepts healthy individuals
No

Comments about the studied populations

Antiretroviral-naïve participants (defined as no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection) prior to enrolment with plasma HIV-1 RNA ≥1,000 c/mL at screening. Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

Health status

Study type

Interventional (clinical trial)

Enrollment

180

Allocation

Non-randomized

Intervention model

Parallel Assignment

Intervention model description

Not provided

Masking

Open label

Masking description

None (Open Label)

Frequency of administration

Studied LA-formulation(s)

Studied route(s) of administration

Use case

Treatment

Key results

Proprietary excipients used

No proprietary excipient used

Novel excipients or existing excipients at a concentration above Inactive Ingredients Database (IID) for the specified route of administration

The novel excipient poloxamer 338 (P338) is used in the final G001 Rilpivirine clinical formulation. Following both an in-vitro mammalian chromosome aberration and an Ames test, it was considered to be non-genotoxic with no evidence for mutagenicity. Further P338 fertility, genotoxicity and development studies have been conducted with no negative effects, in addition to a 6-week and 9- month minipig repeat-dose toxicity study. No adverse local or systemic toxicity was reported in the minipigs at 100mg/month (Margin of Exposure:19).

Residual solvents used

No residual solvent used

There are either no relevant patents or these were not yet submitted to LAPaL

Publications

Bares SH, Scarsi KK. A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. Curr Opin HIV AIDS. 2022 Jan 1;17(1):22-31. doi: https://doi.org/10.1097/COH.0000000000000708. PMID: 34871188; PMCID: PMC8694245.

Purpose of review

Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). This review focuses on phase 3 clinical trial results and implementation considerations for these long-acting ART and PrEP strategies.

Recent findings

Long-acting CAB and RPV administered every 4 weeks demonstrated noninferiority to oral ART through week 96 in both the ATLAS and FLAIR studies, whereas ATLAS-2M found similar efficacy through 96 weeks when the long-acting injectable ART was administered every 8 weeks instead of every 4 weeks. For prevention, two phase 3 trials were stopped early due to fewer incident HIV infections in participants receiving long-acting CAB every 8 weeks compared with daily oral tenofovir disoproxil fumarate–emtricitabine for PrEP. The long-acting therapies were well tolerated across all clinical trials.

Summary

Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. Implementation challenges persist, and data are urgently needed in populations who may benefit most from long-acting therapy, including adolescents, pregnant individuals, and those with barriers to medication adherence.

Additional documents

No documents were uploaded

Useful links

• FDA Approves Cabenuva and Vocabria for the Treatment of HIV-1 Infection

• CABENUVA FDA Highlights of Prescribing Information

Not provided