A Phase 1b/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Efavaleukin Alfa in Adult Subjects with Steroid Refractory Chronic Graft versus Host Disease.

Amgen, Inc.0 个研究点目标入组 134 人开始时间: 2017年9月18日最近更新: 2021年12月21日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Amgen, Inc.
入组人数: 134

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•Subject or legally acceptable representative has provided informed consent prior to initiation of any study specific activities/procedures.
•Subject is an adult (= 18 years old at the time of signing the informed consent).
•Subject is a recipient of an allogeneic hematopoietic stem cell transplant (HSCT).
•Subject has moderate to severe steroid-refractory cGVHD as defined by all of the following criteria:
•Diagnosed with cGVHD per the 2014 cGVHD NIH Consensus Criteria
•(Jagasia, 2015; Appendix 8) within the past 2 years prior to screening.
•Steroid refractory cGVHD, defined as having persistent signs and symptoms of cGVHD despite = 4 weeks of prednisone (or equivalent) dosed at = 0.25 mg/kg/day (or = 0.5 mg/kg every other day) within the 12 months prior to screening.
•Moderate to severe cGVHD (in accordance with 2014 cGVHD NIH
•Consensus Criteria [Jagasia, 2015; Appendix 9]) at screening with
•involvement of at least one of the following organs at the screening and baseline visits: skin, mouth, eyes, gastrointestinal (GI) tract, liver,
•lungs, and joint and fascia.
•Subject has received no more than 3 previous treatments for cGVHD, excluding topical agents.
•Treatment with corticosteroids is considered a treatment for cGVHD and should be included in determining the number of previous treatments.
•- Lines of therapy consisting of concurrent medications or interventions (eg, tacrolimus and corticosteroids; ECP and corticosteroids) count as 2 separate treatments.
•If cGVHD has worsened during a taper of immunosuppressive agents, restoring the agents to therapeutic level is permitted and does not count as an additional treatment.
•Subject may be receiving corticosteroid therapy provided that the dose is = 1 mg/kg/day of systemic prednisone or equivalent and has been stable for at least 2 weeks prior to first dose of efavaleukin alfa.
•Subject may be receiving other non-corticosteroid immunosuppressive
•therapies provided that the immunosuppressant dose is stable for at least 2 weeks prior to first dose of efavaleukin alfa. Adjustments to dose of calcineurin inhibitor or sirolimus are allowed only to maintain drug levels within therapeutic range.
•Subject has a Karnofsky performance status score = 50%.
•Subject has an estimated life expectancy of > 3 months.
•Subjects must have adequate hepatic function:
•total bilirubin < 2.0 mg/dL (34.2 µmol/L) - exception permitted in participants with Gilbert's Syndrome
•aspartate transaminase [AST; SGOT]/Alanine transaminase [ALT; SGPT] = 2x upper limit of normal (ULN), unless hepatic dysfunction is a manifestation of presumed cGVHD.
•abnormal LFTs in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD. If LFT abnormalities are deemed consistent with hepatic cGVHD by the investigator, a liver biopsy will not be mandated.
•Subjects must have adequate pulmonary function defined as: forced expiratory volume in 1 second (FEV1) = 50% or hemoglobin-adjusted diffusion capacity for carbon monoxide (DLCO Hb) = 40% of predicted, unless pulmonary dysfunction is deemed to be due to cGVHD.
•Subjects must have adequate renal function defined as: a calculated glomerular filtration rate of > 50 mL/min/1.73 m2 using the MDRD formula.
•Subjects must have adequate cardiac function defined as:: no history within 6 months prior to screening of myocardial infarction, unstable angina, New York Heart

排除标准

•Subject is concurrently receiving treatment with calcineurin-inhibitor plus sirolimus
•Subject has received ibrutinib, imatinib, bortezomib, entospletinib, ruxolitinib or other JAK inhibitor, or treatment with any investigational drug or device within 4 weeks prior to starting efavaleukin alfa.
•Subject has received the following therapies considered investigational for treament of cGVHD: imatinib, ibrutinib, bortezomib, ruxolitnib, entospletinib, within 4 weeks prior to enrollment or is currently receiving treatment in another investigational drug or device study.
•Subject has received treatment with T-cell depleting, B-cell depleting or IL-2 signaling targeted medication
•Subject has received treatment with T regulatory cell expanding therapies (ie ECP, PUVA, UVB, adoptively transferred T regulatory cells) within 4 weeks prior to starting efavaleukin alfa.
•Subject has received a donor lymphocyte infusion within 12 weeks prior to starting efavaleukin alfa.
•Subject with active morphologic relapse/progression of hematologic malignancy post transplantation. Persistent CLL early after transplantation that subsequently entered remission will not be excluded.
•Subject has a history of malignancy, other than the indication for hematopoietic cell transplantation, with the following exceptions:
•adequately treated nonmelanoma skin cancers without current evidence of disease
•adequately treated cervical carcinoma in situ without current evidence of disease
•adequately treated breast ductal cancer in situ without current evidence of disease
•any malignancy treated with curative intent and with no evidence of active disease present for more than 5 years prior to screening and felt to be at low risk for recurrence by the treating physician.
•Subject has a history of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
•Subject has an active infection requiring treatment with IV antibiotics or has been hospitalized for treatment of an active infection in the 4 weeks prior to starting efavaleukin alfa.
•Subject has known history of active tuberculosis.
•Subject has a positive test for tuberculosis during screening defined as either:
•positive purified derivative (PPD) (= 5 mm of induration at 48 to 72 hours after test is placed)
•positive Quantiferon or T-SPOT test
•subjects with a positive PPD and a history of Bacillus Calmette-Guérin vaccination are allowed with a negative Quantiferon test and negative chest x ray
•subjects with a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or subjects with a positive or indeterminate Quantiferon test are allowed if they have ALL of the following at screening:
•ono symptoms per tuberculosis worksheet provided by Amgen
•odocument history of a completed course of adequate prophylaxis (completed treatment for latent tuberculosis [TB] per local standard of care prior to the start of investigational product
•ono known exposure to a case of active tuberculosis after most recent prophylaxis
•onegative chest X-ray
•Subject is positive for hepatitis B surface antigen, hepatitis B core antibody (confirmed by hepatitis B deoxyribonucleic acid [DNA] polymerase chain reaction [PCR] test) or detectable hepatitis C virus ribonucleic acid (RNA) by PCR (screening is generally done by hepatitis C antibody [HepCAb], followed by hepatitis C virus RNA by PCR if HepCAb is positive). Subjects with a history of hepatitis B vaccination without history of hep

研究者

发起方

Amgen, Inc.

相似试验

进行中（未招募）

1 期

Clinical study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of AMG 510KRAS p.G12C mutant advanced NSCLC, CRC, and other solid tumorsMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

EUCTR2018-001400-11-PTAmgen Inc.733

进行中（未招募）

1 期

Clinical study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of AMG 510

EUCTR2018-001400-11-ROAmgen Inc.733

进行中（未招募）

1 期

A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)KRAS p.G12C Mutant Advanced Solid TumorsMedDRA version: 21.1Level: PTClassification code: 10061873Term: Non-small cell lung cancer Class: 100000004864

CTIS2024-511798-31-00Amgen Inc.932

进行中（未招募）

1 期

EUCTR2018-001400-11-ATAmgen Inc.791

进行中（未招募）

1 期

Clinical study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of AMG 510

EUCTR2018-001400-11-HUAmgen Inc.733