A Phase III, Randomized, Multicenter, Parallel-group, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-Acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch from an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected Antiretroviral Therapy Naive Adult Participants (study 201584, FLAIR)

This study, the First Long-Acting Injectable Regimen * FLAIR study, is being
conducted to establish if HIV-1 infected adult participants whose virus is
virologically suppressed on an integrase inhibitor single tablet regimen (INI
STR) will remain suppressed after switching to a two-drug intramuscular (IM)
longacting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV) once every
4 weeks. In this study, the INI STR will be limited to
abacavir/dolutegravir/lamivudine (ABC/DTG/3TC, trade name: Triumeq) for
HLA-B*5701 gene negative subjects. Subjects who are HLA-B*5701 positive at the
screening visit are allowed to enter the study on DTG and an approved
dual-nucleoside reverse transcriptase inhibitor (NRTI) scheme that does not
contain abacavir.
The FLAIR study is being conducted in parallel with the 201585 (ATLAS) study
with the aim to pool data generated from FLAIR and ATLAS, in order to evaluate
key program objectives.

Primary:
To demonstrate the non-inferior antiviral activity of switching to a two drug
CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks compared to remaining on
ABC/DTG/3TC (or DTG and an approved dual-NRTI scheme) over 48 weeks.
Secondary:
To demonstrate the antiviral and immunologic activity, safety and tolerability,
effects on fasting lipids, development of viral resistance, pharmacokinetics,
pain and injection site reactions, quality of life, treatment satisfaction and
acceptance, health status.

Open label multicenter parallel group study of 120 weeks.
1. Induction phase (ABC/DTG/3TC for 20 weeks).
2. Subjects who are HLA-B*5701 positive at the screening visit are allowed to
enter the study on DTG and an approved dual-nucleoside reverse transcriptase
inhibitor (NRTI) scheme that does not contain abacavir.
3. Participants who have an HIV-1 RNA <50 c/mL will be randomized (1:1) into
the maintenance phase to either continue ABC/DTG/3TC (or DTG and an approved
NRTI scheme) for at least 100 weeks or to begin oral therapy with CAB 30 mg +
RPV 25 mg once daily for 4 weeks, followed (in case of acceptable tolerability)
by CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks (loading dose
600/900 mg resp.).
4. Participants from the ABC/DTG/3TC arm (or DTG and an approved NRTI scheme)
who successfully complete Week 100 will be given the option to switch to the LA
arm in the extension phase (no predefined length).
5. Participants on the CAB LA + RPV LA regimen in the maintenance phase will
enter the extension phase as well.
6. Any participant who receives at least a single dose of CAB LA and/or RPV LA
and discontinues the CAB LA + RPV LA regimen for any reason will enter a 52
week follow-up phase on suppressive highly active antiretroviral therapy.
Independent Data Monitoring Committee.
620 participants.

Treatment with ABC/DTG/3TC and CAB LA + RPV LA.

Risk: Adverse events of the study medication. Resistance development.
Burden:
Visits every 4 weeks in case of LA injections. In case of tablets: every 4-8
weeks up to extension period, during extension period every 4 weeks.
Al least 33 visits.
Physical examination: every visit.
Blood draws (occasionally fasting): nearly every visit (avg 40 ml blood).
Pregnancy test: every visit.
ECG: 10-11 times.
Questionnaires:SSRS (Columbia) 20 times, others up to 17 times.
Optional: blood sample for pharmacogenetics, PK sampling.