計劃書編號SNX-301-020
試驗執行中
2024-05-09 - 2027-10-31
Phase III
召募中2
ICD-10D48.1
結締及其他軟組織性態未明之腫瘤
ICD-9727.02
腱鞘巨細胞腫瘤
一項第 3 期、多中心、隨機分配、雙盲試驗，旨在評估 Emactuzumab 與安慰劑治療腱鞘巨細胞瘤受試者的安全性和療效
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試驗委託 / 贊助單位名稱
香港商法馬蘇提克產品發展有限公司台灣分公司
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臨床試驗規模
多國多中心
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更新日期
2026/02/01
試驗主持人及試驗醫院
適應症
腱鞘巨細胞瘤
試驗目的
本試驗的目的是評估 TGCT 受試者靜脈輸注 Emactuzumab 相較於安慰劑的安全性和療效。
藥品名稱
液劑
主成份
Emactuzumab
劑型
970
劑量
250mg/10ml
評估指標
主要
•本試驗的主要療效目標是在盲性期基於 ORR 評估 Emactuzumab自治療開始起 6 個月相較於安慰劑的治療效果
評估指標
•基於獨立盲性中央審查，依據
第 1.1 版 RECIST 確定的自治療開始起 6 個月內 ORR
•本試驗的主要療效目標是在盲性期基於 ORR 評估 Emactuzumab自治療開始起 6 個月相較於安慰劑的治療效果
評估指標
•基於獨立盲性中央審查，依據
第 1.1 版 RECIST 確定的自治療開始起 6 個月內 ORR
主要納入條件
5.1Inclusion Criteria
Subjects are eligible to be included in the study only if all of the following criteria apply:
1.Written informed consent.
2.Biopsy-confirmed (standard of care diagnosis history) local or diffuse TGCT where a multidisciplinary tumour board or equivalent* determines:
•Surgical resection is predicted to be associated with worsening functional limitations due to surgical damage to the joint and adjacent soft tissues; and/or
•Subject presents with an anticipated high risk of early recurrence after surgery; and/or
•Surgical treatment is not expected to improve the clinical outcomes of the subject; and/or
•Any other significant morbidity that would impede surgery for their TGCT.ie other reasons why surgery for TGCT is not recommended.
*The multidisciplinary tumour board or equivalent must comprise at least 2 individuals: the Investigator plus at least one other qualified physician (orthopaedic surgeon or medical oncologist) not involved in this study.
3.Measurable disease: longest diameter ≥20 mm on central read.
4.Age >12 years and weight ≥30 kg.
Note: in Sweden and The Netherlands, subjects must be aged ≥16 years and adolescent subjects aged 16-17 years must fulfil Tanner Stage 5 criteria. In other countries, legislation requirements for adulthood consideration will determine inclusion age limit for study entry.
5.Adequate organ and bone marrow function: haemoglobin (Hb) >10.0 g/dL, neutrophils >1.5 × 109/L and platelets >100 × 109/L.
6.Minimum mean score of 4 on NRS for Worst Pain during 7 days prior to randomisation, based upon a minimum of 4 days of completed diary data. If applicable, subjects should be on a stable analgesic regime for the period of 2 weeks prior to randomisation.
7.Minimum mean score of 4 on NRS for Worst Stiffness during 7 days prior to randomisation, based upon a minimum of 4 days of completed diary data.
8.Women of childbearing potential (WOCBP) must have a negative urine and serum pregnancy test prior to starting treatment. WOCBP must agree to use a highly effective method of contraception throughout the treatment period and for 7 months after discontinuation of treatment. Acceptable methods of contraception are:
•Hormonal contraception associated with inhibition of ovulation. Oral contraception and parenteral hormonal contraceptives (patches, injectables and implants) that may be affected by enzyme-inducing drugs should only be used in combination with a barrier method.
•Intrauterine device (IUD).
•Intrauterine hormone-releasing system (IUS).
•Bilateral tubal occlusion.
•Vasectomised partner.
•Sexual abstinence, in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
All men with partners of childbearing potential or whose partners are pregnant must use barrier contraception for the duration of dosing and for 5 months post-dosing, unless surgically sterile.
9.For Open-Label Phase ONLY:
Adult subjects only:
•Subjects who were randomised and completed the 6-month double-blind phase of the study
•Subjects deemed to have progression of disease by either:
oobjective progressive disease as measured locally by MRI
oor symptomatic progression by clinical evaluation in the opinion of the investigator
•Patients will be assessed as having progressed and are treated with emactuzumab after Visit 10 (Day 181) and up to Visit 13 (Day 541) per Schedule of Assessments.
•Patients have not been unblinded to treatment prior to Visit 10 (Day 181)
•Patients have not had surgery for TGCT prior to Visit 10 (Day 181)
•Toxicities to prior blinded treatment have resolved to grade 1 or less (see exclusion criteria 7) prior to starting open-label treatment.
•At least 3 months have elapsed between open-label and double-blind treatments
Subjects are eligible to be included in the study only if all of the following criteria apply:
1.Written informed consent.
2.Biopsy-confirmed (standard of care diagnosis history) local or diffuse TGCT where a multidisciplinary tumour board or equivalent* determines:
•Surgical resection is predicted to be associated with worsening functional limitations due to surgical damage to the joint and adjacent soft tissues; and/or
•Subject presents with an anticipated high risk of early recurrence after surgery; and/or
•Surgical treatment is not expected to improve the clinical outcomes of the subject; and/or
•Any other significant morbidity that would impede surgery for their TGCT.ie other reasons why surgery for TGCT is not recommended.
*The multidisciplinary tumour board or equivalent must comprise at least 2 individuals: the Investigator plus at least one other qualified physician (orthopaedic surgeon or medical oncologist) not involved in this study.
3.Measurable disease: longest diameter ≥20 mm on central read.
4.Age >12 years and weight ≥30 kg.
Note: in Sweden and The Netherlands, subjects must be aged ≥16 years and adolescent subjects aged 16-17 years must fulfil Tanner Stage 5 criteria. In other countries, legislation requirements for adulthood consideration will determine inclusion age limit for study entry.
5.Adequate organ and bone marrow function: haemoglobin (Hb) >10.0 g/dL, neutrophils >1.5 × 109/L and platelets >100 × 109/L.
6.Minimum mean score of 4 on NRS for Worst Pain during 7 days prior to randomisation, based upon a minimum of 4 days of completed diary data. If applicable, subjects should be on a stable analgesic regime for the period of 2 weeks prior to randomisation.
7.Minimum mean score of 4 on NRS for Worst Stiffness during 7 days prior to randomisation, based upon a minimum of 4 days of completed diary data.
8.Women of childbearing potential (WOCBP) must have a negative urine and serum pregnancy test prior to starting treatment. WOCBP must agree to use a highly effective method of contraception throughout the treatment period and for 7 months after discontinuation of treatment. Acceptable methods of contraception are:
•Hormonal contraception associated with inhibition of ovulation. Oral contraception and parenteral hormonal contraceptives (patches, injectables and implants) that may be affected by enzyme-inducing drugs should only be used in combination with a barrier method.
•Intrauterine device (IUD).
•Intrauterine hormone-releasing system (IUS).
•Bilateral tubal occlusion.
•Vasectomised partner.
•Sexual abstinence, in line with the preferred and usual lifestyle of the subject. Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
All men with partners of childbearing potential or whose partners are pregnant must use barrier contraception for the duration of dosing and for 5 months post-dosing, unless surgically sterile.
9.For Open-Label Phase ONLY:
Adult subjects only:
•Subjects who were randomised and completed the 6-month double-blind phase of the study
•Subjects deemed to have progression of disease by either:
oobjective progressive disease as measured locally by MRI
oor symptomatic progression by clinical evaluation in the opinion of the investigator
•Patients will be assessed as having progressed and are treated with emactuzumab after Visit 10 (Day 181) and up to Visit 13 (Day 541) per Schedule of Assessments.
•Patients have not been unblinded to treatment prior to Visit 10 (Day 181)
•Patients have not had surgery for TGCT prior to Visit 10 (Day 181)
•Toxicities to prior blinded treatment have resolved to grade 1 or less (see exclusion criteria 7) prior to starting open-label treatment.
•At least 3 months have elapsed between open-label and double-blind treatments
主要排除條件
5.2Exclusion Criteria
Subjects are excluded from the study if any of the following criteria apply:
1.Pregnant, planning to be pregnant or breast feeding.
2.Medical conditions, requiring systemic immunosuppression. Any systemic treatment for these conditions (eg, glucocorticoids) is not allowed within 4 weeks of Screening and during the study. Patients with auto-immune disease, including but not limited to autoimmune thyroid disease, systemic lupus erythematosus, Sjögren’s syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, idiopathic pulmonary fibrosis (including bronchiolitis obliterans organizing pneumonia), and inflammatory bowel disease, are to be excluded from study participation.
3.Metastatic TGCT.
4.TGCT currently affecting multiple joints.
5.Previous use of systemic therapy (investigational or approved) targeting CSF 1 or CSF 1R, any multi-tyrosine kinase inhibitor (eg nilotinib and imatinib) or any investigational systemic therapy, within 3 months of Screening or 5 half-lives, whichever is longer.
6.Nilotinib, imatinib, other chemotherapy, radiotherapy, or investigational therapy within 4 weeks of Screening.
7.Clinically significant toxicity from a previous treatment not resolved to Grade 1or less.
8.Current or chronic history of liver disease. This includes, but is not limited to, hepatitis virus infections, drug- or alcohol-related liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, haemochromatosis, Wilson’s disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease which in the opinion of the Investigator is considered clinically significant.
9.Renal function: creatinine clearance <60 mL/min (Cockcroft-Gault formula).
10.Liver function: ALT and / or AST >3.0 × ULN; OR total bilirubin >1.5 × ULN (excluding Gilbert syndrome).
11.Within 6 months of baseline has experienced: clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) Class III or IV, or pulmonary disease (NYHA Criteria 1994), including severe thromboembolic event; incompletely healed clinically significant wounds, including bone fractures; pathological fracture or significant hypercalcaemia.
12.Clinically significant active infection requiring systemic antibiotic treatment. Rescreening may occur any time after 7 days post-completion of treatment.
13.Systemic antiretroviral therapy within 3 months of baseline.
14.Other active cancer that requires concurrent or planned treatment or history of malignancy other than TGCT, unless there is the expectation that the malignancy has been cured, and tumour specific treatment for the malignancy has not been administered within the previous 5 years.
15.Planned surgery during the course of the study with the exception of dental treatment (see exclusion criterion 11 for wound healing).
16.Inability to comply with the study procedures.
17.For the Double-Blind Phase ONLY:
Previous exposure to emactuzumab.
18.Known allergy/hypersensitivity to the active ingredients or to the excipients.
Subjects are excluded from the study if any of the following criteria apply:
1.Pregnant, planning to be pregnant or breast feeding.
2.Medical conditions, requiring systemic immunosuppression. Any systemic treatment for these conditions (eg, glucocorticoids) is not allowed within 4 weeks of Screening and during the study. Patients with auto-immune disease, including but not limited to autoimmune thyroid disease, systemic lupus erythematosus, Sjögren’s syndrome, glomerulonephritis, multiple sclerosis, rheumatoid arthritis, vasculitis, idiopathic pulmonary fibrosis (including bronchiolitis obliterans organizing pneumonia), and inflammatory bowel disease, are to be excluded from study participation.
3.Metastatic TGCT.
4.TGCT currently affecting multiple joints.
5.Previous use of systemic therapy (investigational or approved) targeting CSF 1 or CSF 1R, any multi-tyrosine kinase inhibitor (eg nilotinib and imatinib) or any investigational systemic therapy, within 3 months of Screening or 5 half-lives, whichever is longer.
6.Nilotinib, imatinib, other chemotherapy, radiotherapy, or investigational therapy within 4 weeks of Screening.
7.Clinically significant toxicity from a previous treatment not resolved to Grade 1or less.
8.Current or chronic history of liver disease. This includes, but is not limited to, hepatitis virus infections, drug- or alcohol-related liver disease, non-alcoholic steatohepatitis, autoimmune hepatitis, haemochromatosis, Wilson’s disease, α-1 antitrypsin deficiency, primary biliary cholangitis, primary sclerosing cholangitis, or any other liver disease which in the opinion of the Investigator is considered clinically significant.
9.Renal function: creatinine clearance <60 mL/min (Cockcroft-Gault formula).
10.Liver function: ALT and / or AST >3.0 × ULN; OR total bilirubin >1.5 × ULN (excluding Gilbert syndrome).
11.Within 6 months of baseline has experienced: clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) Class III or IV, or pulmonary disease (NYHA Criteria 1994), including severe thromboembolic event; incompletely healed clinically significant wounds, including bone fractures; pathological fracture or significant hypercalcaemia.
12.Clinically significant active infection requiring systemic antibiotic treatment. Rescreening may occur any time after 7 days post-completion of treatment.
13.Systemic antiretroviral therapy within 3 months of baseline.
14.Other active cancer that requires concurrent or planned treatment or history of malignancy other than TGCT, unless there is the expectation that the malignancy has been cured, and tumour specific treatment for the malignancy has not been administered within the previous 5 years.
15.Planned surgery during the course of the study with the exception of dental treatment (see exclusion criterion 11 for wound healing).
16.Inability to comply with the study procedures.
17.For the Double-Blind Phase ONLY:
Previous exposure to emactuzumab.
18.Known allergy/hypersensitivity to the active ingredients or to the excipients.
試驗計畫預計收納受試者人數
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台灣人數
4 人
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全球人數
160 人
