Early Neutralizing Antibodies in Infants Living With HIV to Enhance Their Life (2) (ENABLE 2)
A Phase 1/2 Trial Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of Subcutaneous ePGT121v1-LS in Combination With VRC07-523LS, Added to Standard Antiretroviral Therapy in Infants Living With HIV
The goal of this clinical trial is to learn if subcutaneous ePGT121v1-LS and VRC07-523-LS added to standard antiretroviral therapy (ART) is safe and helps improve HIV viral suppression in infants living with HIV in Mozambique and Cameroon. The study will also learn how the body processes ePGT121v1-LS and VRC07-523-LS and whether caregivers and health workers find this treatment approach acceptable.
The main questions it aims to answer are:
- Are ePGT121v1-LS and and VRC07-523-LS safe and well tolerated in infants living with HIV?
- Does adding ePGT121v1-LS and VRC07-523-LS to standard ART increase the number of infants who achieve HIV viral suppression by week 48?
- How long does it take participants receiving ePGT121v1-LS and VRC07-523-LS to achieve viral suppression compared with standard treatment alone?
- How does ePGT121v1-LS and VRC07-523-LS behave in the body after repeated subcutaneous injections?
Researchers will compare infants receiving ePGT121v1-LS and VRC07-523-LS plus ART to infants receiving standard ART plus placebo (saline) to see if ePGT121v1-LS improves HIV viral suppression.
Participants will:
- Continue taking standard oral ART.
- Receive 4 subcutaneous injections of ePGT121v1-LS and VRC07-523-LS or placebo every 12 weeks.
- Attend regular clinic visits for safety checks, blood tests, and HIV viral load monitoring.
- Have follow-up visits for 48 weeks.
- Participate in evaluations of treatment adherence and acceptability from the perspective of caregivers and health workers.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
This Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of subcutaneous (SC) ePGT121v1-LS and VRC07-523-LS administered as adjunctive therapy to standard antiretroviral therapy (ART) in infants living with HIV (ILHIV) in South Africa.
Although early ART initiation has significantly improved survival among infants with HIV, achieving sustained virological suppression during infancy remains challenging because of factors including limited pediatric formulations, adherence difficulties, high baseline viral loads, and treatment interruptions. Novel long-acting therapeutic strategies that simplify treatment delivery and enhance antiviral activity may improve outcomes in this vulnerable population.
Broadly neutralizing antibodies (bNAbs) have shown antiviral activity in adults and children living with HIV and may provide additional benefits through prolonged antiviral coverage and immunomodulatory effects. ePGT121v1-LS is a long-acting bNAb directed against the V3 glycan supersite of the HIV-1 envelope and VRC07-523-LS is a bNAb against the CD4 binding site. The LS mutation extends antibody half-life and supports infrequent dosing schedules using SC administration.
This study includes an initial safety lead-in phase followed by a randomized placebo-controlled phase evaluating ePGT121v1-LS and VRC07-523-LS in combination with standard ART. The trial will assess the safety profile and tolerability of repeated SC administrations and will characterize pharmacokinetic parameters following serial dosing in infants. In addition, the study will evaluate the antiviral effect of ePGT121v1-LS and VRC07-523-LS intensification therapy on HIV viral suppression during the first 48 weeks of follow-up.
Exploratory analyses will further assess virological, immunological, and reservoir-related outcomes, including HIV-1 DNA dynamics, anti-drug antibodies, biomarkers and immune responses associated with bNAb exposure. Qualitative assessments will also evaluate the acceptability and feasibility of SC bNAb administration from the perspective of caregivers, healthcare workers, and stakeholders.
The results of this study are intended to inform the development of future pediatric trials evaluating long-acting bNAb-based therapeutic strategies for infants living with HIV.
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
研究連絡先
- 名前：Alfredo Tagarro, PhD
- 電話番号：+34606194888
- メール：alfredo.tagarro@salud.madrid.org
参加基準
適格基準
適格基準
就学可能な年齢
- 子
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Infants from 1 to 365 days old at the time of enrolment.
- Living with HIV-1, diagnosed with an approved assay detecting HIV nucleic acids in blood.
- Weight > 2.5 kg at enrolment.
- ART-naïve or ≤ 30 days of triple ART at screening (not including prophylaxis in HIV-exposed).
- Clinically stable and can be managed as outpatient (participants identified in-hospital can start the trial at their first routine visit).
- Parent or legal guardian able to provide Informed consent (IC).
Exclusion Criteria:
- Participation in other concurrent research studies that, in the opinion of the principal investigator and central team, would interfere with the objectives of this study.
- Previous receipt of bNAbs against HIV.
- Serious Adverse Reactions (SARs) to the investigational medicinal product (IMP) or its components.
- Intravenous (IV) immunoglobulins received within 90 days before IMP administration.
- Any clinically significant acute or chronic illness or condition at screening that, in the opinion of the principal investigator/designee, renders the participant unfit to participate in the study or jeopardizes the safety or rights of the participant. Including, but not restricted to:
- Evidence of active tuberculosis (TB) disease at the time of enrolment.
- Life-threatening condition associated with a high risk of death within 30 days of enrolment, as determined by the study clinician.
- Severe acute malnutrition with complications.
- Severe neurological illness.
- Hemodynamically significant severe congenital heart disease.
- Active malignancies.
- Life-threatening bleeding disorder.
- Use of systemic immunosuppressive drugs within 30 days before first IMP administration. Not exclusionary: nasal steroid spray, inhaled steroids, topical steroids, a single course of oral/parenteral prednisone or equivalent at 2 mg/kg/day, and length of therapy <14 days.
- Unwillingness to have blood drawn
- Unable to receive SC medications.
- Chronic or recurrent urticaria or any other chronic dermatological condition that may be confused with local Adverse Reactions (ARs).
Any social or medical condition in the caregivers that, in the judgement of the investigator, would interfere with protocol adherence, completion of the trial or assessment of safety.
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：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
アクティブコンパレータ：ePGT121v1-LS and VRC07-523-LS
4 injections of the bNAb ePGT121v1-LS and 4 injections of and VRC07-523-LS, separated 12 weeks, plus antiretroviral treatment.
|
Administration of subcutaneous ePGT121v1LS, 4 doses, separate 12 weeks away.
Administration of subcutaneous ePGT121v1LS, 4 doses, separate 12 weeks away.
|
|
プラセボコンパレーター：Placebo (saline)
4 injections of saline, separated 12 weeks, plus antiretroviral treatment.
|
Administration of subcutaneous saline, 4 doses, separate 12 weeks away.
|
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Safety (Serious adverse events)
時間枠：48 weeks
|
Proportion of participants experiencing SAEs throughout the whole trial.
|
48 weeks
|
|
Virological suppression
時間枠：48 weeks
|
|
48 weeks
|
|
Time to virological suppression
時間枠：48 weeks
|
• Time to first virological suppression, defined as the time from randomization to the first post-baseline measurement of plasma HIV-1 RNA < 40 copies/mL.
|
48 weeks
|
|
Tolerability of the treatment (participants who discontinue)
時間枠：48 weeks
|
• Proportion of participants who discontinue due to toxicity or tolerability issues.
|
48 weeks
|
|
Tolerability of the injection
時間枠：1 hour
|
• Median score of pain assessment scale after administration of bNAb (FLACC scale).
|
1 hour
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
PK profile of ePGT121v1-LS and of VRC07-523-LS
時間枠：12 weeks
|
Half-life
|
12 weeks
|
|
Time to sustained virological suppression
時間枠：48 weeks
|
Time from randomization to the first scheduled post-baseline visit at which HIV-1 RNA is < 40 copies/mL, provided that all subsequent scheduled HIV-1 RNA measurements through week 48 also remain < 40 copies/mL.
|
48 weeks
|
|
Longitudinal virological response
時間枠：48 weeks
|
Proportion of participants with HIV-1 RNA < 40 copies/mL at weeks 12, 24, 36, and 48 will be recorded as the endpoint and log change in plasma HIV-1 RNA levels relative to baseline and subsequent pre-dose measurements.
|
48 weeks
|
|
Acceptability
時間枠：48 weeks
|
The acceptability will be assessed through a series of qualitative interviews and limited quantitative assessments.
|
48 weeks
|
|
Adverse events
時間枠：48 weeks
|
Number of and proportion of participants with solicited adverse event (AEs) and laboratory-related AEs.
|
48 weeks
|
その他の成果指標
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
All-cause mortality and number of hospitalizations.
時間枠：48 weeks
|
All-cause mortality and number of hospitalizations.
|
48 weeks
|
|
Clinical features at baseline and during follow-up
時間枠：48 weeks
|
This exploratory objective will include a comprehensive evaluation of different clinical parameters such as demographics (age, gestational age, weight, Prevention of Mother-To-Child Transmission (PMTCT) interventions), HIV disease severity (VL, CD4+ T-cell count/percentage), nutritional status, comorbidities (infectious and non-infectious), and ART (time to initiation, adherence during follow-up).
|
48 weeks
|
|
HIV-1 DNA
時間枠：48 weeks
|
The concentration of intact and defective HIV-1 proviral DNA, expressed as copies per million of peripheral blood mononuclear cells (PBMCs), measured by intact proviral DNA assay (IPDA) and quantified at baseline and week 48
|
48 weeks
|
|
Anti-drug antibodies (ADAs)
時間枠：48 weeks
|
The titers of ADAs will be quantified at baseline and week 48 to assess whether the development of host antibodies (anti-bNAbs) contributes to virological failure among infants who experience viral rebound by week 48, compared to infants with virological suppression at week 48.
|
48 weeks
|
|
Neutralizing Activity
時間枠：48 weeks
|
Neutralization titers will be calculated as IC50 (50% inhibitory concentration) and IC80 (80% inhibitory concentration) by TZM-bl luciferase reporter assay.
In vitro susceptibility of env-pseudotyped viruses derived from all participants at baseline and from those experiencing breakthrough viremia at week 48 will be used to establish whether in vitro susceptibility predicts virological success
|
48 weeks
|
|
Immunophenotype
時間枠：48 weeks
|
Cellular immunophenotype will be measured using AIM-ICS flow cytometry to determine the activation status and cytokine production of T-cells and NK cells.
|
48 weeks
|
|
ADCC and intracellular p24 expression
時間枠：24 weeks
|
Change from baseline in bNAb-mediated effector function, as measured by ADCC assays, quantified by percentage of target cell lysis and percentage of activated NK cells (e.g., CD107a+) at predefined timepoints.
|
24 weeks
|
|
Biomarkers
時間枠：48 weeks
|
Association between sTREM-1 and adverse outcomes (mortality)
|
48 weeks
|
協力者と研究者
協力者
協力者
研究記録日
主要日程の研究
研究開始 (推定)
研究開始
一次修了 (推定)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
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
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
その他の研究ID番号
- 101190620_2
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?
IPD プランの説明
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
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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