膝関節滑膜炎および変形性関節症を有する被験者における関節内4P004注射の安全性と有効性を調査する試験 (INFLAM MOTION)
多施設共同、無作為化、二重盲検、プラセボ対照、膝滑膜炎および変形性膝関節症を有する被験者における関節内投与4P004の有効性と安全性を検討する概念実証試験
This phase 2a trial is an international, multicenter, randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of one single intra-articular (IA) injection of 4P004 or placebo in:
- patients between 40 and 80 years of age,
- with synovitis and grade 2 to 4 osteoarthritis (OA) of the knee according to Kellgren and Lawrence (KL) classification.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Arizona
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Tucson、Arizona、アメリカ、85712-2805
- Tucson Orthopaedic Institute
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Illinois
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Chicago、Illinois、アメリカ、60611
- Northwestern University Feinberg School of Medicine
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Massachusetts
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Burlington、Massachusetts、アメリカ、01803
- Skylight Health Research Burlington
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Ajax、カナダ
- Durham Bone and Joint Specialists
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London、カナダ
- SJHC London Rheumatology Centre
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Québec、カナダ
- G.R.M.O. (Groupe de recherche en maladies osseuses) Inc
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-
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A Coruña、スペイン
- Complejo Hospitalario Universitario de A Coruna - Hospital Universitario de A Coruna
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A Coruña、スペイン、15702
- Clínica Gaias Santiago
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Alicante、スペイン
- HLA Clínica Vistahermosa
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Sabadell、スペイン
- Corporacio Sanitaria Parc Tauli - Hospital de Sabadell
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Santiago de Compostela、スペイン
- Clinica Nuestra Senora de la Esperanza
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Seville、スペイン
- Hospital Quirónsalud Sagrado Corazón
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-
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Frederiksberg、デンマーク
- Parker Institute Bispebjerg, Frederiksberg Hospital
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Herlev、デンマーク
- Sanos Clinic Herlev
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-
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Montpellier、フランス
- CHU Montpellier
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Nice、フランス
- ChU de Nice
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Paris、フランス
- Hôpital Lariboisière
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Paris、フランス
- Hôpital Cochin
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Reims、フランス
- Centre Hospitalier Universitaire CHU de Reims - Hopital Maison Blanche
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Krakow、ポーランド
- Care Access Kraków
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Warsaw、ポーランド
- Centrum Medyczne Reuma Park
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Warsaw、ポーランド
- MICS Centrum Medyczne Warszawa
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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:
- Participants who have the capacity to give informed consent and who are willing to comply with all trial related procedures and assessments.
- Participants between 40 and 80 years of age.
- Female participant of childbearing potential (defined as any woman unless postmenopausal for at least one year or surgically sterile) must use highly effective methods of contraception as defined in the protocol. Highly effective contraceptive measures must be continued throughout the trial until the final visit.
- Bodyweight > 40 kg.
- Body mass index (BMI) ≥ 18.5 and ≤ 35.
- Ambulatory (single assistive devices such as canes allowed).
- Widespread Pain Index (WPI) ≤ 4.
- Pain NRS (0-10) < 4 in the contralateral knee.
- History of OA-related pain of the TK for at least 6 months.
- Moderate to severe pain of the TK the majority of days during the last 3 months as per participant's judgement.
- Moderate to severe pain of the TK on the WOMAC Pain subscale prior to the Randomization visit (V2) complying with: a) Complete WOMAC Pain diary for at least 7 of the last 10 days prior to V2 (including V2/D1 rating which is mandatory), and b) Diary reported WOMAC Pain between 5 and 9 for at least 7 of the last 10 days.
- History of insufficient pain relief, intolerance, or contraindication to NSAIDs, and at least a history of insufficient pain relief from at least one of the following therapies: a) Acetaminophen/paracetamol, b) Opioids including tramadol, or c) Corticosteroids, hyaluronate IA injections (efficacy less than 3 months according to the patient).
- KL grade 2 to 4 on the Schuss radiograph.
- Predominant femorotibial OA based on the OA Research Society International. (OARSI) Atlas reading (Altman & Gold, 2007).
- Presence of synovitis in the TK assessed locally using PDUS, and synovial thickness of ≥ 5 mm evaluated through a longitudinal view of the suprapatellar pouch and axial views of the medial and lateral patellofemoral pouches.
- Negative urine drug screen (performed locally): amphetamines, barbiturates, cocaine.
- CE-MRI Central reading to confirm synovitis with a synovial Semi-Quantitative (SQ) ≥ 9 or a SQ score ≥7 with at least one site with a score ≥ 2.
Exclusion Criteria:
- Pregnant or breastfeeding women.
- Significant malalignment of anatomical axis (medial angle formed by the femur and tibia) of the TK (varus > 10°, valgus > 10°) by radiography.
- Secondary OA such as joint dysplasia, aseptic osteonecrosis, joint infection, acromegaly, Paget disease, hemochromatosis, joint crystal disease or any inflammatory joint disease.
- Any known active infections including skin infections at the site injection or increased predisposition for the development of infections.
- Any partial knee replacement of the TK.
- Acute fracture or IA trauma to the TK within 12 months prior to the screening visit.
- Major knee surgery performed within the previous 12 months or planned during the trial.
- Arthroscopy of the TK within 6 months prior to the screening visit.
- Presence of any painful conditions that could confound accurate assessment of pain from OA in the TK, such as fibromyalgia, peripheral neuropathy or vascular insufficiency.
- Treatment with systemic corticosteroids (other than IA) at a dose greater than 10 mg prednisone or the equivalent per day for more than 7 days within 4 weeks prior to the screening visit.
- Treatment of the TK with any IA injection (including corticosteroids, hyaluronic acid derivatives, Platelet Rich Plasma….) within 24 weeks prior to the screening visit.
- Any treatment with glucosamine, chondroitin sulfate, or other nutraceuticals with potential activity on OA within the previous 3 months prior to the screening visit.
- Treatment with duloxetine for OA (allowed if given for depressive disorders at stable dose since at least 3 months before V1).
- Any significant psychiatric illness unless well controlled since at least 6 months.
- Current treatment with combination of insulin and liraglutide (Xultophy®) or with GLP-1 agonist administered once a week (semaglutide, dulaglutide).
- High-risk of bleeding.
- Congestive Heart Failure stage III or IV in the New York Heart Association classification.
- History or current diagnosis of electrocardiogram ECG abnormalities indicating significant safety risk (such as ischemia, significant cardiac arrhythmias).
- Glycemia < 4.4 mmol/L (or 80 mg/dL) at screening.
- Clinically significant abnormal laboratory test at screening, in particular: haemoglobin <10 g/dL, white blood cell <3000/µL (3.0 Giga/L), absolute neutrophil count <1000/µL (1.0 Giga/L), platelets count <100,000/µL (100 Giga/L), alanine aminotransferase or aspartate aminotransferase >2.5 upper limit of normal (ULN), total bilirubin >1.5 ULN, lipasemia >1 ULN.
- Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, using Chronic Kidney Disease - EPIdemiology (CKD EPI) 2021 Formula.
- Any other abnormal laboratory results that the Investigator believes should preclude the subject's participation in the trial.
- History of hypersensitivity to IMP or excipients (liraglutide or disodium phosphate dihydrate, propylene glycol, phenol).
- Any contraindication for MRI (cardiac pacemaker, deep brain stimulators, intraocular metal, cerebral aneurysm clips, recent stents, cochlear implants, neurostimulators and implantable pumps) or inability to undergo MRI (e.g., body size, leg not fitting in the coil, claustrophobia).
- History of hypersensitivity reactions to a gadolinium-based contrast agent.
- Any CE-MRI Central reading additional diagnoses: posterior meniscal root tears, subchondral insufficiency fractures, osteonecrosis, malignant bone marrow infiltration, solid tumours, and traumatic fracture or bone bruise using ROAMES (Roemer et al., 2020).
- Previous participation in clinical research with a disease-modifying OA drug during the last 2 years.
- Participation in an interventional clinical research trial within 3 months before screening.
- Participants who, in the investigator's judgement, are at risk of falling.
- Participants with a history, or current diagnosis, of pancreatitis, thyroid cancer (including medullary thyroid carcinoma), multiple endocrine neoplasia type-2 (MEN2), diabetic ketoacidosis, type-1 diabetes mellitus (T1DM), inflammatory bowel disease, or diabetic gastroparesis.
- Participants currently, or within the last 10 days, taking any anticoagulant treatment.
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
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：4P004 (2mL)
One IA injection in the knee of 4P004 (2mL) on the day of randomization |
Single intra-articular injection in the knee joint
他の名前：
|
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プラセボコンパレーター：Placebo (NaCl 0.9% 2mL)
One IA injection in the knee of Placebo (NaCl 0.9% 2mL) on the day of randomization |
Single intra-articular injection in the knee joint |
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 |
|---|---|---|
|
Change from Baseline at Week 4 in the weekly average of Target Knee (TK) daily pain intensity using the WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain subscore
時間枠：Baseline and Week 4
|
The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
Baseline and Week 4
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
第2週、第4週、第8週、第12週におけるOMERACT-OARSI レスポンダーの割合（%）
時間枠：2週目、4週目、8週目および12週目
|
2週目、4週目、8週目および12週目
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試験期間中のTEAE（治療発現性有害事象）の発生率と重症度
時間枠：ランダム化から試験終了まで、最長12週間
|
ランダム化から試験終了まで、最長12週間
|
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ベースラインからの絶対変化 - 臨床検査評価（血液学パラメータ）：総血球数（cell/L）
時間枠：無作為化から試験終了まで（最長12週間）
|
無作為化から試験終了まで（最長12週間）
|
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ベースラインからの絶対変化 - 臨床検査評価（血液学パラメータ）：ヘモグロビン（g/L）
時間枠：無作為化から試験終了まで（最長12週間）
|
無作為化から試験終了まで（最長12週間）
|
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ベースラインからの絶対的変化 - 臨床検査評価（血液化学）：AST（U/L）
時間枠：無作為化から試験終了まで（最長12週間）
|
無作為化から試験終了まで（最長12週間）
|
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臨床検査評価 - 血液化学におけるベースラインからの絶対変化：ALT（U/L）
時間枠：無作為化から試験終了まで（最大12週間）
|
無作為化から試験終了まで（最大12週間）
|
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臨床検査評価における血液化学的検査 - リパーゼ（単位：U/L）のベースラインからの絶対的変化
時間枠：無作為化から試験終了まで（最長12週間）
|
無作為化から試験終了まで（最長12週間）
|
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臨床検査評価 - 血液化学検査における空腹時血糖値（mmol/L）のベースラインからの絶対変化
時間枠：無作為化から試験終了まで（最長12週間）
|
無作為化から試験終了まで（最長12週間）
|
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ベースラインからの絶対変化 - 臨床検査評価（血液化学）：総ビリルビン（単位：μmol/L）
時間枠：無作為化から試験終了まで（最長12週間）
|
無作為化から試験終了まで（最長12週間）
|
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バイタルサインのベースラインからの絶対変化：収縮期および拡張期血圧（BP）
時間枠：無作為化から試験終了まで（最長12週間）
|
無作為化から試験終了まで（最長12週間）
|
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バイタルサイン：脈拍数のベースラインからの絶対変化
時間枠：無作為化から試験終了まで（最長12週間）
|
無作為化から試験終了まで（最長12週間）
|
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|
Change from Baseline at Week 2, Week 6, Week 8, Week 10 and Week 12 in the weekly average of TK (Target Knee) daily pain intensity using the WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain subscore
時間枠：Baseline, Week 2, Week 6, Week 8, Week 10 and Week 12
|
The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
Baseline, Week 2, Week 6, Week 8, Week 10 and Week 12
|
|
Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in the NRS (Numeric Rating Scale) pain (scale 0-10) in a nominated pain aggravating activity
時間枠：Baseline, Week 2, Week 4, Week 8 and Week 12
|
The numeric rating scale (NRS) is a pain screening tool, commonly used to assess pain severity at that moment in time, using a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable. |
Baseline, Week 2, Week 4, Week 8 and Week 12
|
|
Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in WOMAC (Western Ontario and McMaster Universities Arthritis Index) subscores and total score
時間枠：Baseline, Week 2, Week 4, Week 8 and Week 12
|
The WOMAC is a questionnaire widely used in the evaluation of knee osteoarthritis. It contains 24 items measuring 3 subscales: physical function (17 items), pain (5 items), and stiffness (2 items). Scores are calculated for each subscale and summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. The sum of the scores for all three subscales gives a total WOMAC score. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
Baseline, Week 2, Week 4, Week 8 and Week 12
|
|
Change from Baseline at Week 2, Week 4, Week 8 and Week 12 in the Patient Global Assessment of Osteoarthritis (PGA-OA)
時間枠：Baseline, Week 2, Week 4, Week 8 and Week 12
|
The PGA-OA is a 1-item questionnaire designed to assess the participant's impression of disease severity adapted from Guy et al., 1976, to the specific disease as a Patient-reported Outcome measurement "Considering all the ways your knee osteoarthritis affects you, how are you doing these last seven days ?". PGA-OA is measured on a 5-point Likert scale, with higher scores indicating worse symptoms (1= "very good" to 5 = "very poor"). |
Baseline, Week 2, Week 4, Week 8 and Week 12
|
協力者と研究者
スポンサー
捜査官
- スタディチェア：Francis Berenbaum, MD, PhD、4
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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
- 4MB-4P004-P-INFLAM
- 2024-518916-38-00 (Ctis)
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
米国で製造され、米国から輸出された製品。
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