2024-518511-19-00招募中3 期
A Phase 3, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Cabotegravir Ultra Long-acting Plus Rilpivirine Ultra Long-acting or Cabotegravir Long-acting Plus Rilpivirine Long-acting in Adults and Adolescents with HIV who are Virologically Suppressed on ART
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 81
- 试验地点
- 35
- 主要终点
- Plasma HIV-1 RNA greater than or equal to 50 copies/mL as per FDA Snapshot algorithm at Month 11 (FAS).
研究概览
简要总结
To demonstrate the non-inferior antiviral activity of CAB ULA + RPV ULA compared to CAB LA + RPV LA in people with HIV who are virally suppressed and ART-experienced.
研究设计
- 分配方式
- Randomized
- 主要目的
- Extension Phase
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 65+ years（18-64 Years, 0-17 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Adults and adolescents with HIV-1 infection aged 12 years or older, at the time of signing the informed consent.
- •The investigator, or a person designated by the investigator, will obtain written informed consent from each study participant and the participant’s assent, when applicable, before any study-specific activity is performed. All legal guardians should be fully informed, and participants should be informed to the fullest extent possible, about the study in language and terms they are able to understand.
- •For participants enrolled in France: a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
- •Staff Study Participant Inclusion Criteria: Be a delegated staff member for the study, either as a physician, nurse, injector, pharmacist, or other appropriate healthcare professional.
- •Staff Study Participant Inclusion Criteria: Be involved in the treatment of participants in the Q2M and/or Q4M treatment arms.
- •Staff Study Participant Inclusion Criteria: Able to provide consent to participate and has the required resource for questionnaire completion and to participate in an interview (SSPs selected for interviews).
- •Staff Study Participant Inclusion Criteria: Have the cognitive ability to complete an online questionnaire and take part in an interview which may last up to 45-minute (only for SSPs selected for interviews).
- •Staff Study Participant Inclusion Criteria: Able to read, write and fully understand the materials in the languages provided in the study.
- •Weight >35 kg.
- •Documented evidence of at least 2 plasma HIV-1 RNA measurements <50 copies/mL in the 12 months prior to Screening: 1 within the 6 to 12-month window, and 1 within 6 months prior to Screening. Participants should also have HIV-1 RNA <50 copies/mL at screening assessment.
- •Must be on current daily oral antiretroviral regimen for at least 6 months uninterrupted 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 treatment failure (HIV-1 RNA ≥200 copies/mL).
- •A participant is eligible to participate if they are not pregnant or breast/chestfeeding, and 1 of the following conditions applies: Is not of childbearing potential
- •A participant is eligible to participate if they are not pregnant or breast/chestfeeding, and 1 of the following conditions applies: Is a person of childbearing potential (POCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in the protocol, prior to, during the study intervention period, and for 52 weeks following the last dose of study intervention administered. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention).
- •A POCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local regulations) at screening and on Day 1 before the first dose of study intervention.
- •If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
排除标准
- •Significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
- •Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting surgery or percutaneous transluminal coronary angioplasty or any clinically significant cardiac disease.
- •Uncontrolled malignancy is always excluded, whereas participants who have controlled malignancies may be included on agreement between the investigator and the medical monitor.
- •History 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.
- •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 take oral or IM medication.
- •Any preexisting physical or mental condition 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.
- •ALT ≥3xULN.
- •Total bilirubin >1.5xULN; For participants with Gilbert’s syndrome can be included with total bilirubin >1.5xULN as long as direct bilirubin is <=1.5xULN.
- •Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice
- •QT interval corrected for heart rate according to Fridericia’s formula (QTcF) >450 msec
- •Use of concomitant medications which are associated with Torsades de Pointes.
- •Participants who are pregnant or breast/chestfeeding or plan to become pregnant or breast/chestfeed during the study
- •Any prior exposure to CAB and/or RPV for treatment or prevention of HIV-1 infection.
- •Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening or any history of receiving long-acting therapy for HIV (including lenacapavir or broadly neutralizing antibodies).
- •Current or anticipated need for chronic anticoagulants, with the exception of low dose acetylsalicylic acid (≤325 mg).
- •Treatment with any of the following agents within 28 days of screening: radiation therapy
- •Treatment with any of the following agents within 28 days of screening: cytotoxic chemotherapeutic agents
- •Treatment with any of the following agents within 28 days of screening: tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid, INH)
- •Treatment with any of the following agents within 28 days of screening: anti-coagulation agents, with the exception of the use of low dose acetylsalicylic acid (≤325 mg)
- •Treatment with any of the following agents within 28 days of screening: immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons. Note: Participants using short-term (e.g., ≤21 days) systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are eligible for enrolment
- •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.
- •Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.
- •Any evidence of an active CDC Stage 3 disease (See CDC classification for HIV-1 Infection 2014 in the protocol), except cutaneous Kaposi’s sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/mm3 are not exclusionary
- •Current enrolment or past participation in any another investigational clinical study or any other type of medical research in which an investigational study intervention (e.g., drug, vaccine, invasive device) was administered within the last 90 days before signing of consent.
- •Current enrolment or past participation in this clinical study.
- •Within 6 months prior to Screening, any plasma HIV-1 RNA measurement >=50 copies/mL
- •Within the 6 to 12-month window prior to Screening, any plasma HIV-1 RNA measurement >=200 copies/mL, or 2 or more plasma HIV-1 RNA measurements >=50 copies/mL
- •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, lipid abnormalities or CPK. A single repeat test is allowed during the screening period to verify a result.
- •eGFR of <30 mL/min/1.73 m2 via refitted, race-neutral CKD-EPIcr_R method (adult participants) or <50 mL/min/1.73 m2 using the Bedside Schwartz equation (adolescent participants).
- •Hemoglobin <9.0 g/dL
- •Absolute Neutrophil Count (ANC) <600 mm3
- •Any evidence of primary resistance based on the presence of any major known INSTI (including CAB) or NNRTI (including RPV) resistance-associated mutation that was obtained from analyses prior to screening, including any historical resistance test result.
- •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) or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment and discussion with Medical Monitor).
- •Unwilling to receive injections, or unable to receive gluteal injections.
- •The participant has gluteal implants or prosthesis; or a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.
- •Adolescents who are wards of the state or government.
- •Staff Study Participant Exclusion Criteria: Not willing to be audio recorded during interviews (only for SSPs selected for interviews).
- •Participants positive for HBsAg are excluded.
- •Participants negative for HBsAb and negative for HBsAg but positive for HBcAb may be excluded based on the following consideration: - Exclude if HBV DNA is detected [either < LLoQ, > ULoQ OR numerical value (i.e., between LLoQ and ULoQ)] - Not excluded if HBV DNA is negative, not detected
- •History of liver cirrhosis with or without hepatitis viral co-infection.
- •Participants determined by the investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrollment 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 enrollment
- •Participants who in the investigator’s judgment, pose a significant suicidality risk. Participant’s history of suicidal behaviour and/or suicidal ideation should be considered when evaluating for suicide risk
研究组 & 干预措施
Vocabria 600 mg prolonged-release suspension for injection
Comparator
干预措施: Vocabria 600 mg prolonged-release suspension for injection (Drug)
REKAMBYS 900 mg prolonged-release suspension for injection
Comparator
干预措施: REKAMBYS 900 mg prolonged-release suspension for injection (Drug)
结局指标
主要结局
Plasma HIV-1 RNA greater than or equal to 50 copies/mL as per FDA Snapshot algorithm at Month 11 (FAS).
Plasma HIV-1 RNA greater than or equal to 50 copies/mL as per FDA Snapshot algorithm at Month 11 (FAS).
次要结局
- 10. Absolute value and change from baseline in CD4+ cell counts over time including Months 11 and 23.
- 11. Grade 2-5 drug-related AEs and SAEs, and Treatment discontinuation due to AEs/injection intolerability over time including Months 11 and 23.
- 6. Plasma CAB and RPV concentrations and plasma PK parameters for CAB and RPV (when evaluable, Ctrough, maximum concentrations post dose [~Cmax], and area under the curve [AUC]).
- 1. Plasma HIV-1 RNA greater than or equal to 50 copies/mL as per FDA Snapshot algorithm at Month 23 FAS.
- 2. Plasma HIV-1 RNA <50 copies/mL at Month 11 and 23 using the FDA Snapshot algorithm (FAS).
- 3. Protocol-defined confirmed virologic failure (CVF, defined as 2 consecutive HIV-1 RNAs >=200 copies/mL) through Months 11 and 23.
- 4. Grade 2-5 drug-related AEs and SAEs and Treatment discontinuation due to AEs/injection intolerability over time including Months 11 and 23.
- 5. Treatment emergent genotypic and phenotypic resistance to CAB, RPV through Months 11 and 23.
- 7. Plasma HIV-1-RNA greater than or equal to 50 copies/mL as per FDA Snapshot algorithm at Months 11 and 23 (FAS- adolescents).
- 8. Plasma HIV-1 RNA <50 copies/mL at Months 11 and 23 using the FDA Snapshot algorithm (FAS-adolescents).
- 9. Protocol-defined confirmed virologic failure (CVF, defined as 2 consecutive HIV-1 RNAs >=200 copies/mL) through Months 11 and 23.
研究者
EU GSK Clinical Trials Call Center
Scientific
Viiv Healthcare UK Limited
研究点 (35)
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