En studie för att utvärdera farmakokinetiken, säkerheten och tolerabiliteten av en ny formulering av kabotegravir långverkande administrerat intramuskulärt i ett 4-månaders doseringsintervall (Q4M)
En fas 2b enkelarmsstudie med upprepad dos för att utvärdera den farmakokinetiska profilen, säkerheten och tolerabiliteten hos en ny formulering av Cabotegravir LA som injiceras intramuskulärt Q4M hos ungdomar och vuxna deltagare med risk för hiv-förvärv
This study will evaluate the pharmacokinetics (PK), safety, and tolerability of a new formulation of Cabotegravir (CAB) dosed every 4-months (Q4M) for pre-exposure prophylaxis (PrEP) in participants at risk of HIV-1 acquisition.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
Kontakter och platser
Studieorter
-
-
Alabama
-
Birmingham, Alabama, Förenta staterna, 35222
- GSK Investigational Site
-
-
California
-
Los Angeles, California, Förenta staterna, 90069
- GSK Investigational Site
-
Los Angeles, California, Förenta staterna, 90027
- GSK Investigational Site
-
Los Angeles, California, Förenta staterna, 90036
- GSK Investigational Site
-
Los Angeles, California, Förenta staterna, 90035
- GSK Investigational Site
-
Palm Springs, California, Förenta staterna, 92262
- GSK Investigational Site
-
-
Florida
-
Doral, Florida, Förenta staterna, 33172-2513
- GSK Investigational Site
-
Ft. Pierce, Florida, Förenta staterna, 34982-7148
- GSK Investigational Site
-
Orlando, Florida, Förenta staterna, 32803-1851
- GSK Investigational Site
-
West Palm Beach, Florida, Förenta staterna, 33407
- GSK Investigational Site
-
-
Illinois
-
Chicago, Illinois, Förenta staterna, 60612-7230
- GSK Investigational Site
-
-
Louisiana
-
New Orleans, Louisiana, Förenta staterna, 70112
- GSK Investigational Site
-
-
Massachusetts
-
Springfield, Massachusetts, Förenta staterna, 01105
- GSK Investigational Site
-
-
Michigan
-
Berkley, Michigan, Förenta staterna, 48072
- GSK Investigational Site
-
-
Missouri
-
Kansas City, Missouri, Förenta staterna, 64111
- GSK Investigational Site
-
-
Nevada
-
Las Vegas, Nevada, Förenta staterna, 89119
- GSK Investigational Site
-
-
New York
-
Hawthorne, New York, Förenta staterna, 10532-2140
- GSK Investigational Site
-
New York, New York, Förenta staterna, 10029
- GSK Investigational Site
-
-
North Carolina
-
Greensboro, North Carolina, Förenta staterna, 27401-1209
- GSK Investigational Site
-
-
Ohio
-
Cincinnati, Ohio, Förenta staterna, 45267
- GSK Investigational Site
-
Columbus, Ohio, Förenta staterna, 43210
- GSK Investigational Site
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, Förenta staterna, 15212
- GSK Investigational Site
-
-
Texas
-
Dallas, Texas, Förenta staterna, 75246-2004
- GSK Investigational Site
-
Fort Worth, Texas, Förenta staterna, 76104
- GSK Investigational Site
-
-
Washington
-
Seattle, Washington, Förenta staterna, 98104
- GSK Investigational Site
-
-
-
-
-
San Juan, Puerto Rico, 909
- GSK Investigational Site
-
San Juan, Puerto Rico, 00909
- GSK Investigational Site
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- At the time of obtaining informed consent, adolescent and adult participants weighing at least 35 kg.
- Participants must have a nonreactive HIV test at Screening (rapid test, nonrapid HIV immunoassay, and HIV RNA) and enrollment (a rapid test, nonrapid HIV immunoassay, and HIV RNA).
- Participants who are at risk of acquiring HIV, defined as having had anal or vaginal sex in the past 6 months.
- Participants who are overtly healthy as determined by medical evaluation by a responsible and experienced physician, including medical history, physical examination, laboratory tests and cardiac monitoring at the time of screening.
- No alcohol or substance use that, in the opinion of the study investigator and medical monitor, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records).
- Participants who have received oral PrEP are eligible, but they must discontinue oral PrEP within 10 days of Day 1 visit.
- Male or female at birth, (transgender individuals are not excluded). Contraceptive use should align with local regulations. Participants assigned female at birth must not be pregnant or breastfeeding and must either not be of childbearing potential (POCBP) or use highly effective contraception. A POCBP must have a negative pregnancy test within 30 days before dosing.
- Participants must be >=16 years old, of legal age to consent to sexual intercourse, and capable of giving written informed consent. Adolescents must provide written informed assent/consent and/or obtain parental/guardian consent if not of legal age, as per site SOPs and IRB/EC policies.
Exclusion Criteria:
-
One or more reactive or positive HIV test results at Screening or Enrollment, even if HIV infection was not confirmed.
-
Participants who are breastfeeding or plan to become pregnant or breastfeed during the study.
-
Alanine aminotransferase (ALT) >=3 times the upper limit of normal (ULN).
-
Evidence of active Hepatitis B virus (HBV) infection.
- Participants positive for HBsAg or HBV DNA are excluded.
- Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.
-
Unstable liver disease, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
-
History of clinically relevant hepatitis within last 6 months.
-
Known history of liver cirrhosis with or without viral hepatitis co-infection.
-
Participants with Hepatitis C virus (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, and will not require treatment prior to the primary endpoint (e.g., Month 13).
-
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:
i. Fib-4 score greater than (>) 3.25 is exclusionary. ii. Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation. Fibrosis 4 score Formula: (Age x AST) / (Platelets x (sqr [ ALT]) It is approved by the Medical Monitor.
-
-
Estimated glomerular filtration rate of <30 mL/min/1.73 m^2 via CKD-EPIcr_R (2021) method.
-
Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
-
Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 [triglycerides or lipid abnormalities].
-
Participants determined by the Investigator to have a high risk of seizures, A participant with a prior history of seizure may be considered for enrolment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment.
-
Participant is currently participating in or has participated in a study with a compound or device that is not commercially available within 30 days of signing informed consent, unless permission from the Medical Monitor is granted.
-
Presence of any history of allergy/sensitivity to any of the study drug.
-
Inflammatory skin conditions that compromise the safety of IM injections, per the discretion of the investigator.
-
Participant has an implant/enhancement (including fillers) at the area of proposed injection (e.g., gluteus medius); or tattoo or other dermatological condition overlying the area for IM (e.g., gluteus medius) or any other area which may significantly interfere with interpretation of injection site reactions.
-
Current or anticipated need for chronic anti-coagulants or active coagulopathy (primary or iatrogenic) which would contraindicate IM injection.
-
Ongoing or clinically relevant pancreatitis.
-
Clinically significant cardiovascular disease or history of clinically significant cardiovascular disease.
-
All participants will be screened for STIs (e.g., chlamydia, gonorrhea, trichomoniasis, syphilis). Participants with untreated infections are excluded. Participants may be rescreened at least 24 hours after completion of STI treatment.
-
History or presence of sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
-
Ongoing uncontrolled malignancy is excluded, whereas participants who have controlled localized malignancies may be included on agreement between the investigator and the Medical Monitor.
-
Participants who in the investigator's judgment, poses a significant suicidality risk.
-
Any pre-existing physical or mental condition (including substance abuse disorder) which, in the opinion of the Investigator or the medical monitor, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
-
Any condition which, in the opinion of the Investigator or the medical monitor, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive IM medication.
-
Co-enrollment in any other interventional research study or other concurrent studies which may have interfered with this study (as provided by self-report or other available documentation). Exceptions for non-interventional studies may be made if appropriate after consultation with the Medical Monitor.
-
Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
-
Use of antiretroviral therapy (ART) for Postexposure Prophylaxis within the 90 days prior to Day 1.
-
Use of CAB LA for PrEP at any time prior to Screening.
-
Exposure to an experimental drug or experimental vaccine within either 28 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 the first dose of IP.
-
Anticipated need for HCV therapy with interferon or any drugs that have potential for adverse drug:drug interactions with study treatment throughout the entire study period.
-
Treatment with an HIV-1 preventive vaccine within 90 days of Screening.
-
Participant is unlikely to adhere to the study procedures, keep appointments, is planning to relocate during the study, or remain on study through to its conclusion.
-
Participants who are considered high-risk, meeting at least one of the following criteria:
- Participant who has exchanged condomless sex for goods or money within the past 12 months prior to Screening.
- Participant who has used recreational intravenous drugs within the past 12 months prior to Screening.
- Participant who has participated in Chemsex practice (such as the use of cocaine, crack cocaine, methamphetamine, ketamine, 3,4-methlenedioxy-methamphetamine, GHB, mephedrone or prescription drugs apart from those prescribed by a licensed provider) within the past 6 months prior to Screening.
- Participant with any STI in the last 6 months also reporting any partners for condomless sex.
- Participant who has condomless sex with a serodiscordant partner who has a detectable viral load or is not on ART.
- Participant with any other behavior assessed by the investigator as high-risk sexual behavior.
-
Participant has in the last 14 days prior to Screening presented with signs and symptoms, which, in the opinion of the investigator, are suggestive of acute HIV infection. Participants may only be enrolled if clinical suspicion of HIV is ruled out with non-reactive results.
-
Participant becomes a ward of state (e.g., child in care).
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Övrig
- Tilldelning: Randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: CAB Group
Participants receive lead-in injections comprising cabotegravir LA during month one and injections of a new formulation of CAB LA at Month 3, Month 5 and every 4 months thereafter to Month 29. |
Injections administered IM gluteal. Injections administered IM gluteal. |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
CAB trough concentrations for target of 1.05 microgram per milliliter (μg/mL) for men and 1.39 μg/mL for women
Tidsram: From Month 13 to Month 25
|
CAB trough concentrations are evaluated at or above the target of 1.05 μg/mL for men and 1.39 μg/mL for women, once steady state has been achieved, but no earlier than Month 13 of the study. |
From Month 13 to Month 25
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Andel deltagare med bekräftade incidenter med hiv-infektioner
Tidsram: Upp till månad 33
|
Upp till månad 33
|
|
|
Andel deltagare med laboratorieavvikelser
Tidsram: Upp till månad 33
|
Upp till månad 33
|
|
|
Andel deltagare med förändringar i laboratorieparametrar
Tidsram: Upp till månad 33
|
Upp till månad 33
|
|
|
CAB trough concentrations for target of 0.672 μg/mL for men and 0.683 μg/mL for women
Tidsram: At Month 1
|
CAB trough concentrations are evaluated at or above the target of 0.672 μg/mL for men and 0.683 μg/mL for women. |
At Month 1
|
|
CAB trough concentrations for target of 1.05 μg/mL for men and 1.39 μg/mL for women following loading dose
Tidsram: From Month 3 to Month 33
|
CAB trough concentrations are evaluated at or above the target of 1.05 μg/mL for men and 1.39 μg/mL for women. |
From Month 3 to Month 33
|
|
CAB plasma concentrations
Tidsram: At Day 1, Day 1+1Week (W), Month (M) 1, M1+1W, M2, M3, M3+1W, M4, M5, M5+1W, M6, M7, M8, M9, M9+1W, M10, M11, M13, M13+1W, M17, M17+1W, M21, M25, M29, and M33
|
Blood samples are collected by visit. |
At Day 1, Day 1+1Week (W), Month (M) 1, M1+1W, M2, M3, M3+1W, M4, M5, M5+1W, M6, M7, M8, M9, M9+1W, M10, M11, M13, M13+1W, M17, M17+1W, M21, M25, M29, and M33
|
|
CAB trough concentrations for target of 4x PA-IC90
Tidsram: At Months 1, 3, 5, 9, 13, 17, 21, 25, 29, and 33
|
CAB trough concentrations are evaluated at or above the target of 4 times (4x) PA-IC90. PA-IC90 is defined as protein-adjusted concentration at which 90% inhibition of viral replication is achieved. |
At Months 1, 3, 5, 9, 13, 17, 21, 25, 29, and 33
|
|
Percentage of participants with Study Medication Satisfaction Questionnaire Status version (SMSQs) results
Tidsram: From Month 1 up to Month 33
|
SMSQs is a self-completion measure which is evaluating 11-items (i.e., satisfaction, side effects, demands, convenience, flexibility, understanding, lifestyle, recommend, continue, easy or difficult, discomfort or pain). SMSQs is self-administered at each planned study visit and prior to the study drug administration. |
From Month 1 up to Month 33
|
|
Percentage of participants with Adverse events (AEs)
Tidsram: Up to Month 33
|
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. |
Up to Month 33
|
|
Percentage of participants with AEs by severity
Tidsram: Up to Month 33
|
Severity is graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening. |
Up to Month 33
|
|
Percentage of participants with laboratory abnormalities by severity
Tidsram: Up to Month 33
|
Severity is graded according to the DAIDS grading criteria, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening. |
Up to Month 33
|
Samarbetspartners och utredare
Sponsor
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Blodburna infektioner
- Urogenitala sjukdomar
- Genitala sjukdomar
- Immunsystemets sjukdomar
- Infektioner
- RNA-virusinfektioner
- Virussjukdomar
- Smittsamma sjukdomar
- Sexuellt överförbara sjukdomar, virala
- Sexuellt överförbara sjukdomar
- Lentivirusinfektioner
- Retroviridae-infektioner
- Immunologiska bristsyndrom
- HIV-infektioner
Andra studie-ID-nummer
- 219230
- 2024-000061-24 (EudraCT-nummer)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
Study sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.viiv-studyregister.com/documents/About_ViiV_Patient_Level_Data_Sharing_Final_25Sep2023.pdf
Tidsram för IPD-delning
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Kriterier för IPD Sharing Access
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
IPD-delning som stöder informationstyp
- STUDY_PROTOCOL
- SAV
- ICF
- CSR
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Studerar en amerikansk FDA-reglerad produktprodukt
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .