Phase 2b, Open-label, Multicenter, Rollover Study to Assess Antiviral Activity and Safety of Long-acting Cabotegravir (CAB LA) Plus Long-acting Rilpivirine (RPV LA), Administered Every 2 Months (Q2M), in Human Immunodeficiency Virus (HIV)- Positive Subjects From the LATTE Study



Status:Recruiting
Conditions:HIV / AIDS, HIV / AIDS
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:18 - Any
Updated:2/28/2019
Start Date:August 20, 2018
End Date:January 11, 2021
Contact:US GSK Clinical Trials Call Center
Email:GSKClinicalSupportHD@gsk.com
Phone:877-379-3718

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A Phase IIb, Multicenter, Open-label, Rollover Study Evaluating the Efficacy, Safety and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every Two Months in HIV-1 Infected Adults Who Are Virologically Suppressed and Participated in Study LAI116482

This study (POLAR), is designed to assess the antiviral activity and safety of CAB LA plus
RPV LA, administered Q2M, in approximately 100 adult HIV-1 infected, antiretroviral (ART)
experienced subjects. Subjects will rollover from the NCT01641809(LATTE) study, who have
completed minimum duration of Week 312 and with demonstrated HIV-1 ribonucleic acid (RNA)
suppression (<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 subjects 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). Duration of study will vary from country to country, until regiment
receives regulatory approval and becomes commercially available. The study plans to enroll
approximately 100 subjects. Any subject who receives at least one dose of CAB LA and/or RPV
LA and discontinues the CAB LA plus RPV LA regimen for any reason will enter a 52-week
Long-Term Follow-Up (LTFU) phase. Those subjects must remain on suppressive highly active
antiretroviral therapy (HAART) for at least 52 weeks after the last dose of CAB LA and or RPV
LA.


Inclusion Criteria:

- Aged 18 years or older (or >=19 where required by local regulatory agencies), at the
time of signing the informed consent.

- A female subject is eligible to participate if she is not pregnant (as confirmed by a
negative urine human chorionic gonadotrophin [hCG] test at Day 1), not lactating, and
at least with one of following conditions.

- 1.Non-reproductive potential defined as, Pre-menopausal females with one of the
following conditions as documented tubal ligation; Documented hysteroscopic tubal
occlusion procedure with follow-up confirmation of bilateral tubal occlusion,
Hysterectomy, Documented Bilateral Oophorectomy.

- Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a
blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels
consistent with menopause (refer to laboratory reference ranges for confirmatory
levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is
in doubt will be required to use one of the highly effective contraception methods if
they wish to continue their HRT during the study. Otherwise, they must discontinue HRT
to allow confirmation of post-menopausal status prior to study enrolment.

- 2.Reproductive potential and agrees to follow one of the options listed in the
Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of
Reproductive Potential (FRP) from 30 days prior to the first dose of study medication,
throughout the study, for at least 30 days after discontinuation of all oral study
medications, and for at least 52 weeks after discontinuation of CAB LA and RPV LA.

- The investigator is responsible for ensuring that subjects understand how to properly
use the methods of contraception.

- Capable of giving signed informed consent.

- Must have been on oral CAB 30 mg plus RPV 25 mg regimen through at minimum Week 300 of
the LATTE study as per LATTE protocol dosing requirements and until Day 1 of the POLAR
study. Any disruptions in dosing during LATTE must be discussed with the Medical
Monitor for a final determination of eligibility.

- Plasma HIV-1 RNA <50 c/mL at Week 300. If subject has plasma HIV-1 RNA >= 50 c/mL at
Week 300 in LATTE, a single repeat to determine eligibility may be allowed ONLY after
consultation with the medical monitor.

Exclusion Criteria:

- During the last 6 months of participation in LATTE, consecutive (2 or more sequential)
plasma HIV-1 RNA measurements >=50 c/mL.

- During the last 6 months of participation in LATTE, any HIV-1 RNA measurement >=200
c/mL.

- Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3
disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy.

- Subjects with moderate to severe hepatic impairment determined by Child-Pugh
classification.

- Any pre-existing physical or mental condition (including substance use disorder)
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 subject.

- Subjects determined by the Investigator to have a high risk of seizures, including
subjects with an unstable or poorly controlled seizure disorder. A subject with a
prior history of seizure may be considered for enrolment if the Investigator believes
the risk of seizure recurrence is low.

- Subjects who, in the investigator's judgment, pose a significant suicide risk.
Subject's recent history of suicidal behavior and/or suicidal ideation should be
considered when evaluating for suicide risk.

- Subject has a tattoo or other dermatological condition overlying the gluteus region
which may interfere with interpretation of injection site reactions.

- Evidence of Hepatitis B virus (HBV) infection based on the results of testing for
Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B
surface antibody (anti-HBs) and HBV DNA as follows; Subjects positive for HBsAg are
excluded; subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg
status) and positive for HBV DNA are excluded.

- Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be
excluded, however Investigators must carefully assess if therapy specific for HCV
infection is required; subjects who are anticipated to require HCV treatment within 12
months must be excluded. (HCV treatment on study may be permitted, following
consultation with the medical monitor).

- Subjects with HCV co-infection will be allowed entry into this study if: Liver enzymes
meet entry criteria; HCV Disease has undergone appropriate work-up, and is not
advanced.

- Additional information (where available) on subjects, with HCV coinfection at
screening should include results from any liver biopsy, Fibroscan, ultrasound, or
other fibrosis evaluation, history of cirrhosis or other decompensated liver disease,
prior treatment, and timing/plan for HCV treatment.

- In the event that recent biopsy or imaging data is not available or inconclusive, the
fibrosis- 4 (Fib-4) score will be used to verify eligibility where Fib-4 score >3.25
is exclusionary; Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation where
the Fibrosis 4 Score Formula: age multiplied by aspartate amino transferase (AST)
divided by platelets multiplied by square of alanine aminotransferase (ALT).

- Unstable liver disease (as defined by any of the following: presence of ascites,
encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or
persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of
Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver
disease per investigator assessment).

- History of liver cirrhosis with or without hepatitis viral co-infection.

- Ongoing or clinically relevant pancreatitis.

- Clinically significant cardiovascular disease, as defined by history/evidence of
congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery
bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty
(PTCA) or any clinically significant cardiac disease.

- Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or
resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial
neoplasia; other localized malignancies require agreement between the investigator and
the Study medical monitor for inclusion of the subject prior to randomization.

- 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 receive study medication.

- History or presence of allergy or intolerance to the study drugs or their components
or drugs of their class. In addition, if heparin is used during pharmacokinetic (PK)
sampling, subjects with a history of sensitivity to heparin or heparin-induced
thrombocytopenia must not be enrolled.

- Current or anticipated need for chronic anti-coagulation with the exception of the use
of low dose acetylsalicylic acid (<=325 mg) or hereditary coagulation and platelet
disorders such as hemophilia or Von Willebrand Disease.

- Corrected QT interval (QTc (Bazett)) >450 millisecond (msec) or QTc (Bazett) >480 msec
for subjects with bundle branch block.

- Any verified Grade 4 laboratory abnormality over the last 6 months in LATTE. A single
repeat test is allowed to verify a result.

- Any acute laboratory abnormality over the last 6 months in LATTE, which, in the
opinion of the investigator, would preclude the subject's participation in the study
of an investigational compound.

- ALT>=5 times upper limit of normal (ULN) or ALT >= 3 times ULN and bilirubin >=
1.5xULN (with >35% direct bilirubin) over the last 6 months in LATTE.

- Exposure to an experimental drug (with the exception of those in the LATTE study
including CAB and RPV) or experimental vaccine within either 30 days, 5 half-lives of
the test agent, or twice the duration of the biological effect of the test agent,
whichever is longer, prior to Day 1 of this study.

- Treatment with any of the following agents within 28 days of Day 1: radiation therapy,
cytotoxic chemotherapeutic agents, tuberculosis therapy with the exception of
isoniazid (isonicotinylhydrazid [INH]); anti-coagulation agents.

- Immunomodulators that alter immune responses such as chronic systemic corticosteroids,
interleukins, or interferons. Note: Subjects using short-term (e.g. <=21 days)
systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are
eligible for enrolment.

- Use of medications which are associated with Torsade de Pointes must be discussed with
the Medical Monitor to determine eligibility.

- Subjects receiving any prohibited medication and who are unwilling or unable to switch
to an alternate medication. Any prohibited medications that decrease CAB, RPV and/or
DTG concentrations should be discontinued for a minimum of four weeks or a minimum of
three half-lives (whichever is longer) prior to the first dose and any other
prohibited medications should be discontinued for a minimum of two weeks or a minimum
of three half-lives (whichever is longer) prior to the first dose.
We found this trial at
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New York, New York 10032
Principal Investigator: Martin H Markowitz
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Principal Investigator: Cheryl L Newman
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Austin, Texas 78705
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Bakersfield, California 93309
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Beverly Hills, California 90211
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Buffalo, New York 14263
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Charleston, South Carolina 29425
Principal Investigator: Eric G Meissner
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Dallas, Texas 75230
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Denver, Colorado 80206
Principal Investigator: Mia Scott
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Fort Lauderdale, Florida 33308
Principal Investigator: Gary J Richmond
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Fort Pierce, Florida 34982
Principal Investigator: Moti N Ramgopal
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Indianapolis, Indiana 46202
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Macon, Georgia 31201
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Savannah, Georgia 31405
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Principal Investigator: Joss J. De Wet
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Principal Investigator: Gary L. Simon
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Principal Investigator: Olayemi O Osiyemi
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