Efficacy and Safety of Adalimumab for the Treatment of Ocular Inflammation (PANDA-U)
Efficacy and Safety of Adalimumab in Pediatric Non-Infectious Uveitis: A Multicenter Ambispective Single-Arm Clinical Trial
This study aims to evaluate the clinical efficacy and safety of adalimumab in pediatric non-infectious uveitis and to generate domestic real-world evidence (RWE), thereby establishing a clinical foundation for label expansion and reimbursement coverage.
調査の概要
詳細な説明
Background: Although anti-TNFα agents play a crucial role globally in managing refractory non-infectious uveitis, adalimumab was removed from the approved indication for pediatric uveitis in South Korea several years ago-unlike adult uveitis-making domestic prescription exceptionally difficult. Meanwhile, indications for pediatric idiopathic arthritis and pediatric Crohn's disease remain approved domestically, highlighting an urgent need to establish objective evidence to resolve this regulatory discrepancy. Furthermore, as a substantial number of pediatric patients in Korea are already receiving off-label, non-reimbursed adalimumab treatment, their real-world data serve both as evidence of efficacy and safety and as direct proof of this institutional imbalance.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前:mieun kim
- 電話番号:+82-2-2148-7664
- メール:mieun2728.kim@samsung.com
研究場所
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Seoul、韓国、06351
- Samsung Medical Center
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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
Inclusion Criteria:
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For the Prospective New-User Cohort, verification of Inclusion Criteria 1 through 6 is required.
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For the Retrospective (Switch) Cohort, verification of Inclusion Criteria 1 through 7 is required.
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Pediatric patients aged 2 years and < 18 years.
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Diagnosed with non-infectious anterior uveitis, intermediate uveitis, posterior uveitis, or panuveitis.
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Active intraocular inflammation demonstrated by anterior chamber (AC) cell grade ≥ 1+ (defined as 6 cells per 1 mm\times 1 mm field) according to the SUN (Standardization of Uveitis Nomenclature) criteria, or active posterior segment lesions persistently observed on at least two consecutive assessments despite 12 weeks of treatment with methotrexate and corticosteroids (systemic or topical) prior to screening (SUN grade maintained on 2 occasions, adapted from the SYCAMORE trial definition of active disease).
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Inadequate response to corticosteroid therapy or other immunosuppressive agents (e.g., methotrexate [MTX]), or inability to continue treatment due to unacceptable toxicity/intolerance.
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Written informed consent obtained from the subject's legal representative (parent or legal guardian) and written pediatric assent obtained according to applicable age-specific regulatory and institutional guidelines.
[Prospective De Novo Cohort]
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Patients initiating adalimumab for the first time (adalimumab-naïve).
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[Retrospective / Prospective Cohort] 6. Patients currently on maintenance therapy with adalimumab (including extended dosing intervals, such as every other week [Q2W] or every 3-4 weeks) who require at least 1 additional year of treatment.
7. Patients who agree to switch to the investigational product and adhere to a standard every-other-week (Q2W / once every 2 weeks) administration schedule at the time of study enrollment.
Exclusion Criteria:
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For the Prospective New-User Cohort, verification of Exclusion Criteria 1 through 22 is required.
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For the Retrospective (Switch) Cohort, verification of Exclusion Criteria 1 through 24 is required.
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Patients with uveitis associated with juvenile idiopathic arthritis (JIA) or pediatric Crohn's disease indicated for adalimumab
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Individuals with infectious uveitis or non-immunological intraocular inflammation resulting from trauma, surgery, etc., within 30 days prior to screening
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Individuals with active tuberculosis, untreated latent tuberculosis, sepsis, opportunistic infections, or other severe active infections, or those at high risk for such infections
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Individuals with a history of hypersensitivity to adalimumab or any of its excipients
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Individuals instilling topical glucocorticoids more than 6 times per eye per day, or currently receiving oral prednisone (or its equivalent) at a dose exceeding 0.2 mg/kg/day (adapted from the SYCAMORE criteria)
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Individuals with active malignancy, lymphoproliferative disorders, demyelinating disease (e.g., multiple sclerosis, Guillain-Barré syndrome), or a history of other progressive or degenerative neurological disorders
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Patients who have received TNF inhibitors other than the investigational product
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Patients with New York Heart Association (NYHA) Class III/IV cardiac disease
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Individuals with uncontrolled viral infections, including active hepatitis B or hepatitis C
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Individuals who have received a live vaccine (including live-attenuated vaccines) within 30 days prior to screening, or who are scheduled to receive one during the study period
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Individuals who are pregnant or breastfeeding, or women of childbearing potential (WOCBP) who do not agree to use highly effective contraception*
*A highly effective method of contraception is defined as one that results in a low failure rate of less than 1% per year when used consistently and correctly, and includes: combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; and sexual abstinence.
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Individuals who have received other biologic agents within 5 half-lives prior to screening
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Individuals with a family member who has active tuberculosis, or who have a history of close contact with an individual with active tuberculosis
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Individuals with a major infection requiring antibiotic therapy within 30 days prior to screening
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Individuals with diabetes mellitus deemed uncontrolled by the investigator, or persistently uncontrolled severe hypertension (> 95th percentile for height and age)
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Individuals with a history of malignancy, or a history of solid organ, bone marrow, or corneal transplantation
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Individuals with a history of ocular surgery (e.g., cataract surgery) within 3 months prior to screening
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Individuals who have received intraocular or periocular corticosteroid injections within 30 days prior to screening
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Individuals with a history of ocular herpes simplex or herpes zoster infection
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Individuals with laboratory values evaluated during screening that meet any of the following criteria:
A. Hemoglobin < 8.0 g/dL B. WBC < 4.0 × 10³/µL C. ANC < 1.0 × 10³/µL D. Platelet count < 100 × 10³/µL E. AST or ALT > 2 × ULN
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Individuals weighing less than 15 kg
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Individuals otherwise deemed unsuitable for study participation in the judgment of the investigator
[Retrospective / Prospective Cohort-Specific Criteria]
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Inability to confirm disease activity (e.g., SUN grading) at the initial start of adalimumab treatment and subsequent treatment response via medical record review.
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Patients whose adalimumab dosage has been tapered to near-discontinuation (i.e., dosing intervals substantially exceeding once every 4 weeks) or for whom the treating physician deems the standard maintenance regimen (once every 2 weeks) clinically inappropriate.
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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:単一グループの割り当て
- 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:Prospective Treatment-Naïve Cohort and
Patients initiating adalimumab for the first time receive the investigational product (Yuflyma Pen Inj., subcutaneous adalimumab biosimilar) prospectively for 12 months (approximately 52 weeks) following enrollment. |
Yuflyma Pen Inj. (recombinant adalimumab biosimilar, Celltrion) is administered via subcutaneous (SC) injection with weight-tiered dosing (<30 kg: 20 mg; ≥30 kg: 40 mg).
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実験的:Retrospective (Switch) Cohort
Patients previously maintained on adalimumab prior to study entry and requiring continued treatment for at least one additional year switch to the investigational product (Yuflyma Pen Inj., subcutaneous adalimumab biosimilar) at enrollment. |
Yuflyma Pen Inj. (recombinant adalimumab biosimilar, Celltrion) is administered via subcutaneous (SC) injection with weight-tiered dosing (<30 kg: 20 mg; ≥30 kg: 40 mg).
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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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Treatment Failure Rate in the Prospective Treatment-Naïve Cohort
時間枠:Up to 12 months after adalimumab initiation
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Percentage of participants meeting the criteria for treatment failure. Treatment failure is defined as any of the following: active intraocular inflammation (worsening anterior chamber cell grade, vitreous haze, or new chorioretinal lesions), lack of clinical efficacy requiring addition of new systemic immunosuppressive agents, inability to taper concomitant systemic corticosteroids to target maintenance levels, or discontinuation of the investigational product due to lack of efficacy or unacceptable toxicity. |
Up to 12 months after adalimumab initiation
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Change from Baseline in Medically Important Infections (MIIS) in the Prospective Treatment-Naïve Cohort
時間枠:Baseline and 12 months after adalimumab initiation
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Total count and incidence rate of Medically Important Infections (defined as opportunistic infections, infections requiring intravenous antimicrobial therapy, or infections resulting in hospitalization or death) observed per participant. The change is calculated as the incidence during the 12-month post-initiation period compared to the pre-baseline reference status. |
Baseline and 12 months after adalimumab initiation
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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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Treatment Failure Rate in the Retrospective (Switch) Cohort
時間枠:Up to 12 months post-switch to the investigational product
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Percentage of participants who experience treatment failure following switch to the investigational product. Treatment failure is defined as active intraocular inflammation, necessity to escalate therapy or introduce unpermitted rescue therapies, or drug discontinuation due to lack of efficacy or adverse events. |
Up to 12 months post-switch to the investigational product
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Relapse-Free Survival Rate in the Retrospective (Switch) Cohort
時間枠:At 12, 24, and 36 months post-adalimumab initiation
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Percentage of participants maintaining clinical inactive disease without uveitis recurrence after achieving initial clinical response, estimated using Kaplan-Meier survival methodology at specified annual landmark intervals. |
At 12, 24, and 36 months post-adalimumab initiation
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Cumulative Incidence of Relapse and Management Strategies in the Retrospective (Switch) Cohort
時間枠:Up to 36 months post-adalimumab initiation
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Cumulative incidence of ocular relapse and the distribution of clinical management strategies implemented upon relapse, categorized as dose escalation, administration interval shortening (e.g., from every other week to weekly), or permanent treatment discontinuation. |
Up to 36 months post-adalimumab initiation
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Drug Survival Rate of Adalimumab in the Retrospective (Switch) Cohort
時間枠:Up to 36 months post-adalimumab initiation
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Percentage of participants remaining on adalimumab therapy over time without permanent treatment cessation, evaluated by Kaplan-Meier survival curves. |
Up to 36 months post-adalimumab initiation
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Time to Adalimumab Discontinuation in the Retrospective (Switch) Cohort
時間枠:Up to 36 months post-adalimumab initiation
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Median time (in months) from adalimumab initiation to permanent discontinuation of therapy due to any reason, including loss of response, remission, adverse events, or patient withdrawal. |
Up to 36 months post-adalimumab initiation
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Steroid-Sparing Success Rate in the Retrospective (Switch) Cohort (Pooled Analysis)
時間枠:Up to 36 months post-adalimumab initiation
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Percentage of participants achieving successful systemic steroid-sparing, defined as achieving disease inactivity with oral prednisone (or equivalent) tapered to $\le 0.1\text{ mg/kg/day}$ (or complete cessation) and topical glucocorticoids tapered to $\le 2\text{ drops/day/eye}$. |
Up to 36 months post-adalimumab initiation
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Change from Baseline in Systemic and Topical Corticosteroid Requirements in the Retrospective (Switch) Cohort
時間枠:Baseline (initial adalimumab start) and up to 36 months post-initiation
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Quantitative reduction in daily systemic corticosteroid dose (mg/kg/day of prednisone equivalent) and change in daily frequency of topical ophthalmic corticosteroid instillations per affected eye. |
Baseline (initial adalimumab start) and up to 36 months post-initiation
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Cumulative Incidence of Cataract and Elevated Intraocular Pressure in the Retrospective (Switch) Cohort (Pooled Analysis)
時間枠:Up to 36 months post-adalimumab initiation
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Percentage of participants who develop new-onset or worsening cataract (requiring surgical intervention or clinically significant progression) or elevated intraocular pressure ($\text{IOP} > 21\text{ mmHg}$ or an increase $\ge 10\text{ mmHg}$ from baseline requiring hypotensive medication). |
Up to 36 months post-adalimumab initiation
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Integrated Assessment of Adverse Events Across the Cumulative Exposure Period
時間枠:Up to 48 months (covering up to 36 months retrospective exposure plus 12 months prospective study period)
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Number, incidence rates, and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) assessed per Common Terminology Criteria for Adverse Events (CTCAE) criteria across the combined follow-up duration. |
Up to 48 months (covering up to 36 months retrospective exposure plus 12 months prospective study period)
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協力者と研究者
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 (推定)
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
その他の研究ID番号
- 2026-08-116
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
Individual participant data (IPD) will not be shared publicly to protect patient privacy and comply with relevant personal information protection regulations. Summary data and study results will be made available through peer-reviewed publication.
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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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