HIV-1 感染症の小児および青少年におけるビクテグラビル/レナカパビルの研究
HIV-1 感染症の小児および青少年を対象としたビクテグラビル/レナカパビルの薬物動態、安全性、抗ウイルス活性を評価する第 2/3 相非盲検試験
The goal of this clinical study is to learn about the safety and tolerability of bictegravir (BIC)/lenacapavir (LEN) and to learn how the study drug interacts with the body in virologically suppressed (VS) children and adolescents with human immunodeficiency virus type 1 (HIV-1) on a stable and complex antiretroviral (ARV) regimen. The study will also assess the safe loading dose of LEN and pharmacokinetics (PK) of BIC/LEN.
The primary objectives of this study are:
- To evaluate the steady-state PK of BIC and LEN and confirm the dose of the LEN loading dose and BIC/LEN FDC in VS children and adolescents with HIV-1.
- To evaluate the safety and tolerability of BIC/LEN through Week 24 in VS children and adolescents with HIV-1.
調査の概要
状態
条件
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 3
連絡先と場所
研究場所
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District of Columbia
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Washington D.C.、District of Columbia、アメリカ、20010
- Children's National Hospital
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Florida
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Tampa、Florida、アメリカ、33612
- University of South Florida
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Georgia
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Atlanta、Georgia、アメリカ、30308
- Grady Ponce de Leon Center
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Illinois
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Chicago、Illinois、アメリカ、60614
- Ann and Robert H. Lurie Children's Hospital of Chicago
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Buenos Aires、アルゼンチン、C1141ACG,
- Helios Salud S.A
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Milan、イタリア、20157
- ASST FBF Sacco Ospedale Sacco
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Roma、イタリア、00165
- IRCCS Ospedale Pediatrico Bambino Gesu, UOS Infezioni Complesse e Perinatali
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Madrid、スペイン、28046
- Hospital Universitario La Paz
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Madrid、スペイン、28007
- Hospital General Universitario Gregorio Marano
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Madrid、スペイン、28041
- Hospital Universitario 12 De Octubre
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Cape Town、南アフリカ、7505
- FAMCRU Ukwanda School for Rural Health
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Cape Town、南アフリカ、7646
- Be Part Yoluntu
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Durban、南アフリカ、3629
- Durban International Clinical Research Site, Enhancing Care Foundation
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East London、南アフリカ、5219
- Monti Clinical Research Centre
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Johannesburg、南アフリカ、1862
- Perinatal HIV Research Unit
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Johannesburg、南アフリカ、2038
- Wits RHI Shandukani Research Centre CRS
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Johannesburg、南アフリカ、2112
- Nkanyezi VIDA Research Unit
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Ka-Majosi、南アフリカ、944
- Khomanani Health Research and Wellness Centre
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KwaDukuza、南アフリカ、4449
- Clinical Research Institute of South Africa (CRISA)
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Pretoria、南アフリカ、0087
- The Aurum Institute: Pretoria Clinical Research Centre
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Soshanguve、南アフリカ、0152
- Setshaba Research Centre
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Key Inclusion Criteria:
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Age and body weight at screening:
- Cohort 1: ≥ 12 years to < 18 years weighing ≥ 35 kg.
- Cohort 2: ≥ 6 years to < 12 years weighing ≥ 25 kg to < 35 kg.
- Cohort 3: ≥ 2 years to < 6 years weighing ≥ 10 kg to < 25 kg.
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On a complex ARV regimen. Complex regimens are any ARV therapy that is not a single-tablet regimen taken once daily (eg, > 1 tablet or any other formulation a day).
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Documented plasma HIV-1 ribonucleic acid (RNA) levels must be < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is < 50 copies/mL) in the last 6 months prior to screening (at least 1 measure prior to screening).
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Plasma HIV-1 RNA levels < 50 copies/mL at screening.
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No documented or suspected resistance to integrase strand transfer inhibitors (mutations T66A/I/K, E92G/Q/V, G118R, F121C/Y, G140R, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene).
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The following laboratory parameters at screening:
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Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 using the Bedside Schwartz formula.
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Absolute neutrophil count > 0.50 cells/L (> 500 cells/mm3).
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Hemoglobin ≥ 85 g/L (> 8.5 g/dL).
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Platelets ≥ 50 cells/L (≥ 50,000 cells/mm3).
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Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase)
≤ 5 x upper limit of normal.
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Total bilirubin ≤ 23 μmol/L (≤ 1.5 mg/dL) and direct bilirubin ≤ 7 μmol/L (≤ 0.4 mg/dL).
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Key Exclusion Criteria:
- CD4 cell count < 200 cells/mm^3.
- CD4 percentage < 20%.
- Life expectancy ≤ 1 year.
- An opportunistic illness indicative of Stage 3 HIV diagnosed within the 30 days prior to screening.
- Evidence of active pulmonary or extrapulmonary tuberculosis within 3 months prior to screening.
- Acute hepatitis within 30 days prior to screening.
- Positive hepatitis C virus (HCV) antibody with detectable HCV RNA (participants positive for HCV antibody will have an HCV RNA test performed).
- Positive hepatitis B surface antigen (HBsAg) or positive hepatitis B virus (HBV) core antibody (antibody against hepatitis B core antigen [anti-HBc]) at screening. If a participant is negative for HBsAg and positive for anti-HBc but HBV DNA is undetectable, the participant may be enrolled.
- A history of or current decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding).Current alcohol or substance use judged by the investigator to potentially interfere with the participant's study compliance.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：順次割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Cohort 1: Participants Aged ≥ 12 to < 18 years with Weight ≥ 35 kg: BIC/LEN TOS 75/50 mg FDC
Participants will receive a 2-day oral loading dose of LEN (600 mg) on Days 1 and 2 and daily oral BIC/LEN TOS 75/50 mg starting on Day 1 through Week 48. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
他の名前：
Tablets administered orally without regard to food
他の名前：
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実験的：Cohort 2: Participants Aged ≥ 6 to < 12 years with Weight ≥ 25 kg to < 35 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 2 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
他の名前：
Tablets administered orally without regard to food |
|
実験的：Cohort 3: Participants Aged ≥ 2 to < 6 years with Weight ≥ 10 kg to < 25 kg
All participants will receive a 2-day oral loading dose of LEN, and daily oral BIC and LEN dose starting on Day 1 through Week 48. Dose in cohort 3 to be defined. Following Week 48, participants will have an option to continue BIC/LEN in the extension period. |
Tablets administered orally without regard to food
他の名前：
Tablets administered orally without regard to food |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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24週目までに治療中に発現した有害事象（TEAE）を経験した参加者の割合
時間枠：初回投与日から24週目まで
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初回投与日から24週目まで
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24週目までに治療による臨床検査の異常を経験した参加者の割合
時間枠：初回投与日から24週目まで
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初回投与日から24週目まで
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PK Parameter: Cmax of BIC and LEN at Steady State
時間枠：Day 1 up to Week 24, as appropriate
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Cmax is defined as the maximum observed concentration of drug at steady state. |
Day 1 up to Week 24, as appropriate
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PK Parameter: AUCtau of BIC and LEN at Steady State
時間枠：Day 1 up to Week 24, as appropriate
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AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state. |
Day 1 up to Week 24, as appropriate
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PK Parameter: Ctrough of BIC and LEN at Steady State
時間枠：Day 1 up to Week 24, as appropriate
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Ctrough is defined as the observed drug concentration at the end of the dosing interval at steady state. |
Day 1 up to Week 24, as appropriate
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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48週目までにTEAEを経験した参加者の割合
時間枠：初回投与日から48週目まで
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初回投与日から48週目まで
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48週目までに治療による臨床検査の異常を経験した参加者の割合
時間枠：最初は第48週までの日付です
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最初は第48週までの日付です
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24 週目の血漿 HIV-1 RNA が 50 コピー/mL 未満および 50 コピー/mL 以上の参加者の割合は、米国食品医薬品局 (FDA) 定義のスナップショット アルゴリズムに基づく
時間枠：第24週
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第24週
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米国 FDA 定義のスナップショット アルゴリズムに基づく、48 週目の血漿 HIV-1 RNA が 50 コピー/mL 未満および 50 コピー/mL 以上の参加者の割合
時間枠：48週目
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48週目
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24 週目の分化クラスター 4 (CD4) 細胞数のベースラインからの変化
時間枠：ベースライン、24 週目
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ベースライン、24 週目
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24週目のCD4パーセントのベースラインからの変化
時間枠：ベースライン、24 週目
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ベースライン、24 週目
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48週目のCD4細胞数のベースラインからの変化
時間枠：ベースライン、48 週目
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ベースライン、48 週目
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48週目のCD4パーセントのベースラインからの変化
時間枠：ベースライン、48 週目
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ベースライン、48 週目
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PK Parameter: AUClast for BIC and LEN at Steady State
時間枠：Day 1 up to Week 48, as appropriate
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AUClast is defined as the area under the concentration versus time curve from time zero to the last quantifiable concentration at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Tmax for BIC and LEN at Steady State
時間枠：Day 1 up to Week 48, as appropriate
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Tmax is defined as the time (observed time point) of Cmax at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Tlast for BIC and LEN at Steady State
時間枠：Day 1 up to Week 48, as appropriate
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Tlast is defined as the time (observed time point) of Clast at steady state. Clast is defined as the last measurable concentration (above the quantification limit). |
Day 1 up to Week 48, as appropriate
|
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PK Parameter: T1/2 for BIC and LEN at Steady State
時間枠：Day 1 up to Week 48, as appropriate
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T1/2 is defined as the terminal elimination half-life at steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: CL for BIC and LEN at Steady State
時間枠：Day 1 up to Week 48, as appropriate
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Clearance (CL) is the volume of plasma cleared of drug over a specified time period, at a steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: Vz for BIC and LEN at Steady State
時間枠：Day 1 up to Week 48, as appropriate
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Volume of distribution (Vz) is defined as the extent to in which the drug is distributed in the body tissue, rather than the plasma, to produce the desired effects at a steady state. |
Day 1 up to Week 48, as appropriate
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PK Parameter: λz for BIC and LEN at Steady State
時間枠：Day 1 up to Week 48, as appropriate
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λz is defined as the terminal elimination rate constant, which determines the rate at which the drug will be eliminated from the body after it is absorbed and distributed at a steady state. |
Day 1 up to Week 48, as appropriate
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Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 1 Assessed by Questionnaire
時間枠：Day 1
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 1
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Acceptability and Palatability Summary of LEN Oral Loading Dose at Day 2 Assessed by Questionnaire
時間枠：Day 2
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 2
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Acceptability and Palatability Summary of Oral BIC/LEN Fixed Dose Combination (FDC) at Day 1 Assessed by Questionnaire
時間枠：Day 1
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Day 1
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 4 Assessed by Questionnaire
時間枠：Week 4
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 4
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 24 Assessed by Questionnaire
時間枠：Week 24
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 24
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Acceptability and Palatability Summary of Oral BIC/LEN FDC at Week 48 Assessed by Questionnaire
時間枠：Week 48
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Palatability and acceptability assessed by a numeric response between numbers 1-5. Higher scores indicate better palatability and acceptability. |
Week 48
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協力者と研究者
スポンサー
捜査官
- スタディディレクター：Gilead Study Director、Gilead Sciences
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- GS-US-621-6463
- 2023-509428-16 (その他の識別子：European Medicines Agency)
- 2023 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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