A Safety and Efficacy Study Evaluating CTX112 in Subjects With Refractory Neurologic Autoimmune Disease (CRSP-AID-502)
A Phase 1/2 Dose Evaluation Trial of the Safety and Preliminary Efficacy of Anti-CD19 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX112) in Adult Participants With Refractory Neurologic Autoimmune Disease.
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 trial will evaluate the safety and preliminary efficacy of CTX112 in adult participants with Progressive Multiple Sclerosis (PMS), relapsing Neuromyelitis Optica Spectrum Disorder (NMOSD), relapsing Myelin Oligodendrocyte Glycoprotein Antiody-Associated Disease (MOGAD), refractory AutoImmune Encephalitis (AIE), and refractory Stiff Person Syndrome (SPS). PMS, NMOSD, MOGAD, AIE, and SPS are neurological AIDs where B cells play a significant role. Compartmentalized central nervous system (CNS) inflammation can also occur, leaving a proportion of patients unresponsive to biologics, including clusters of differentiation 19 and 20 (CD19 and CD20)-monoclonal antibodies (mAbs). Both anti-CD19 and anti-CD20 mAbs penetrate the blood-brain barrier (BBB) poorly, limiting the degree of B-cell depletion attainable within the CNS compartment. No curative treatment exists for these conditions, and despite the best available therapies a substantial proportion of patients continue to experience relapses and/or accruing disability and suffer from low quality of life combined with high morbidity and mortality. Current options focus largely on treating or preventing relapses, typically with peripherally acting agents that require repeated parenteral administration. This underscores an urgent need for novel therapies able to cross the BBB and target the CNS B-cell compartment, thereby potentially eliciting a deep immune reset and durable remission in patients who have failed multiple lines of standard therapy. Preliminary evidence suggests that chimeric antigen receptor (CAR) T cells may offer long-lasting benefits, with extended treatment-free remissions and a manageable safety and tolerability profile.CTX112 is a CD19 directed CAR-T cell immunotherapy comprised of allogeneic T cells prepared for the treatment of refractory autoimmune diseases. The cells are collected from healthy adult volunteer donors and are genetically modified ex vivo using CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9) gene editing components (single guide RNA and Cas9 nuclease). As with autologous CD19-targeting CAR T cell therapy, CTX112 has the potential to generate clinical responses in patients with PMS, relapsing NMOSD, relapsing MOGAD, refractory AIE and SPS following a one-time treatment, but with the benefit of immediate availability and without the need for the patient to undergo apheresis for collection of T cells.
This trial may enroll up to 220 participants. The total duration of trial intervention for each participant is up to 5 years.
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
参加基準
適格基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Age ≥18 years and <70 years at screening.
- Body weight >40 kg.
- Participants must voluntarily sign a written informed consent and be willing and able to comply with all trial requirements. Legal authorized representative, additional assent and witness may be used as appropriate.
- Adequate hematologic, renal, liver, cardiac and pulmonary function.
- Participants must agree to use acceptable methods of contraception.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, contraceptive guidelines, and other trial procedures.
- Confirmed diagnosis of PMS, relapsing NMOSD, relapsing MOGAD, refractory AIE, and refractory SPS
Exclusion Criteria:
- Prior treatment with any gene therapy or genetically modified cell therapy.
- Prior solid organ (e.g., heart, liver, kidney, lung) transplant or hematopoietic cell transplant.
- Presence of another clinically significant central nervous (CNS) pathology or another condition that in the opinion of the investigator may increase CART cell-related toxicities or confound disease assessments for the main indication.
- Presence of other active autoimmune disease or other conditions that are likely to pose increased safety risks and/or confound disease assessments, or pose significant risk to those receiving CART cell therapy.
- Presence or history of certain bacterial, viral or fungal infection.
- Malignancy in the last 5 years (with the exception of cancers deemed to be low likelihood for recurrence).
- History or current diagnosis that requires uninterrupted, ongoing anticoagulation.
- Pregnant or lactating.
- Presence or history of disease requiring treatment that is not compatible with the study protocol; presence or history of other conditions that are not compatible with the study protocol.
- History of suicide attempts within 3 years prior to screening.
- Any contraindications to lumbar puncture or MRI scans
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：なし
- 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）
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 |
|---|---|
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実験的：CTX112
リンパ節化化学療法後のIV注入により投与されます
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CTX112 is a CD19-directed T-cell immunotherapy comprised of allogeneic T cells genetically modified ex vivo using CRISPR-Cas9 gene editing components
他の名前：
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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
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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To evaluate the safety of CTX112 in adult participants with neurological autoimmue disorders, including PMS, relapsing NMOSD, relapsing MOGAD, refractory AIE, and refractory SPS.
時間枠：From CTX112 infusion up to 28 days post infusion
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Incidence of dose-limiting toxicities.
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From CTX112 infusion up to 28 days post infusion
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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 |
|---|---|---|
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To assess the pharmacodynamics response to CTX112 in adults with neurological autoimmune disorders
時間枠：From CTX112 infusion up to 24 months post-infusion
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Number of B cells in blood over time.
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From CTX112 infusion up to 24 months post-infusion
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To assess the pharmacokinetics (PK) of CTX112 in adults with neurological autoimmune disorders.
時間枠：From CTX112 infusion up to 24 months post-infusion.
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Levels of CTX112 in blood over time.
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From CTX112 infusion up to 24 months post-infusion.
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To assess the preliminary efficacy of CTX112 in adults with NMOSD.
時間枠：From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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For participants with NMOSD, outcomes include but are not limited to, annualized rate of relapses
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From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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To assess the preliminary efficacy of CTX112 in adults with MOGAD
時間枠：From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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For participants with MOGAD, outcomes include but are not limited to annualized rate of relapses
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From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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To assess the preliminary efficacy of CTX112 in adults with PMS.
時間枠：From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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For participants with PMS, outcomes include but are not limited to, change from baseline in Expanded Disability Status Scale (EDSS) score
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From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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To assess the preliminary efficacy of CTX112 in adults with AIE
時間枠：From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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For participants with AIE, outcomes include but are not limited to, change from baseline in the Modified Rankin Score (mRS) score
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From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
|
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To assess the preliminary efficacy of CTX112 in adults with SPS
時間枠：From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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For participants with SPS, outcomes include but are not limited to, change from baseline in Modified Rankin Score(mRS) score
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From CTX112 infusion up to Month 6, Month 12, Month 18, and Month 24
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協力者と研究者
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
- CRSP-AID-502
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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