TRS로 치료받는 16세 미만 ASI 아동의 새로운 유형을 2년간 추적하며 평가 도구와 비용을 조사하는 시험입니다.

Patients aged 0-15 with SMA type 1, 2 or 3, treated with TRS (nusinersen/risdiplam/onasemnogene abeparvovec/other).

Myogrip (≥ 6 years): precise dynamometric measurement of gripping force, measuring force in Newton up to 90kg with 0.01kg resolution. It's evaluated at D0, M6, M12, M18, and M24 Myopinch (≥ 6 years) : measure thumb-index force up to 15 kg with a resolution of 0.001 kg using a precision sensor equipped with two steel distance blades. It's evaluated at D0, M6, M12, M18, and M24

evaluation of muscle function

Vineland-II (All patients) : is a scale for assessing adaptive behaviors. will be carried out during the telephone call at M1/V2.

All tests are evaluated at D0, and M18 :

Bayley-4 language part (\< 42 months) PVSE (≥ 4 years) CELF-5 (≥ 5 years) Conners-3 (≥ 6 years) AQ (≥ 4 years), EQ (≥ 11 years)

M-CHAT-R (\< 4 years) :

SRS-2 (≥ 2 years)

First-line cognitive assessment

In the event of positive cognitive screening at D0 or M18, a second-line cognitive assessment will be carried out at a subsequent visit. A list of tests is proposed below, but will be adapted according to the tests available at each center.

* EVALO BB (0-2 years) or EVALO (2-6 years) or full CELF-5 (5-18 years) following positive screening in the communication domain of first-line tests (Vineland II communication domain, Bayley 4, CELF-5 pragmatic profile)
* FEE and DSM-5 diagnostic criteria for ADHD (from age 6 only) following positive screening in the attention and executive functions domain of first-line tests (Conners 3, BRIEF)
* M-CHAT-R/F (\< 4 years) or SCQ (≥ 4 years) and ADOS-2 (≥ 12 years) following a positive screening in the area of social cognition and autistic traits on first-line tests (Vineland II, M-CHAT-R, SRS-2, EQ, AQ).

second-line cognitive assessment

All tests are evaluated at D0, M12, and M24 :

Electrocardiogram (ECG) : This examination will be carried out in accordance with the 12 leads recording the following parameters: verification of sinus rhythm, P wave, PR interval, QRS complex (interval), ST segment, T wave, QT complex, heart rate.

Cardiac ultrasound: Non-invasive ultrasound will focus on the following parameters measured from 2-dimensional images, to look for cardiomyopathy and/or structural abnormality:

* end-diastolic/end-systolic diameter/left ventricular ejection fraction
* Septal wall thickness / left ventricular posterior wall
* Fractional shortening 24-hour Holter-ECG : This examination consists of a continuous test recording the heart rhythm for 24 hours.

Cardiac evaluation

Cerebral MRI : Performed at D0, only for patients with ASI type 1 ≥ 6 years, or younger patients for whom the investigator considers that the examination can be performed without sedation or general anesthesia. It will include sequences:

* 3D T1, gradient echo, 1.1 mm voxel, sagittal acquisition
* axial T2, spin-echo, slice thickness 4 mm
* 3D FLAIR, spin-echo, 1 mm voxel, sagittal acquisition Muscular MRI: performed at V1/J0, and V6/M24. The examination will include water-fat imaging (Dixon) in full-body, 3D mode, with proton density weighting and millimeter resolution.

Syde® : evaluated at D0, M6, M12, M24. Patients aged 2 and over will receive the Syde® wearable device to collect their daily activities.

Muscular endurance tests (≥ 6 years) : evaluated at D0, M12, M24 ( only one of 3 tests based on motor function level) oESNHPT : In this test, patients are asked to walk a 10-meter path. oESBBT : In this test, patients have to move 10 blocks over a partition. oESWT: In this test, patients must repeatedly place and remove 9 sticks in 9 holes.

PedsQL Fatigue (≥ 2 years): evaluated at D0, M12, M24. Scale designed to measure fatigue in patients with acute and chronic conditions, as well as in healthy school and community populations.

Fatigue rating scale (≥ 6 years): evaluated at D0, M12, M24. The fatigue assessment scale has 11 numerical points ranging from 0 to 10. The patient is asked to give a rating that best reflects his or her perception of fatigue at that particular moment.

Assessment of activity and muscle fatigue

DDD-pNMD (≥ 2 years) : evaluated at D0, M6, M12, M18, and M24, is a list of 9 questions used by doctors to screen for dysphagia and dysarthria.

NdSSS (All Patients) : evaluated at D0, M6, M12, M18, and M24, is an 8-level scale for assessing swallowing.

TOMASS-c : (≥ 4 years of age, in patients able to eat solids safely, after assessment of the risk of a false route by the speech therapist): this is a score designed to assess mastication when eating a cracker. Age-dependent standards exist for different types of cracker.

- Fluid intake test (\> 110 cm, in patients able to drink a liquid safely, after assessment of the risk of a false route by the speech therapist): swallowing limit.

Assessment of bulbar function

Food survey : The dietary survey questionnaire will be sent to parents at D0 and M18. Parents will be asked to complete it for 3 days before the M6 and M24.

Bioelectrical impedancemetry: Evaluated at M6 and M24. Renal ultrasound: Evaluated at M6, is a non-invasive examination that analyzes the appearance of the kidney and urinary tract.

Dual-energy X-ray absorptiometry (DXA) : Evaluated at M6, it measures body composition using spectral imaging, including fat mass, lean mass and bone mineral density.

Fibroscan : Evaluated at M6 and M24. This examination uses pulse elastography to measure liver elasticity, which provides information on the presence of hepatic fibrosis, and sound attenuation, which provides information on the presence of liver fat overload.

Indirect calorimetry : Evaluated at M6. This device enables precise measurement of Resting Energy Expenditure , Respiratory Quotient and metabolic substrate oxidation.

Evaluation of body composition and metabolism

SMAIS : The questionnaire has been developed specifically for ASI. At D0, M6, M12, M18 and M24.

HUI2 : specializes in preference-based measures of health-related quality of life. At D0, M6, M12, M18 and M24.

Peds QL : is a modular instrument designed to measure health-related quality of life and disease-specific symptoms. At D0, M6, M12, M18 and M24.

Neuromuscular module : 17 disease-related items. It is evaluated at D0, M6, M12, M18 and M24.

Family impact module : It measures parents' reported physical, emotional, social and cognitive functioning, communication and concerns. At D0, M12, and M24.

ASI cost questionnaire: At visit 1 (D0): This questionnaire, completed by the parents, includes information on occupation, parents' working hours and any reduction in them due to the child's pathology, the number of working days missed by the parents or school days missed by the child, and disability-related costs.

Questionnaires

A blood bio collection (optional) will be offered to patients at D0, M6 , M12, M18, M24.

Patients receiving intrathecal injections will also be offered the opportunity to participate in a CSF (cerebrospinal fluid) biocollection (optional).

Biocollection

The tricipital point should be marked on the posterior aspect of the arm, on the midline of the tricipital muscle, midway between the acromion and the radius. At D0, M6, M12, M18 and M24

Skinfold measurement

TRS(뉴시너센/리스디플람/오나셈노진 아베파르보벡/기타)로 치료받는 SMA 1형, 2형 또는 3형이 있는 0~15세 환자.

근육 기능 평가

1차 인지 평가

2차 인지 평가

심장 평가

활동 및 근육 피로 평가

구근 기능 평가

체성분 및 대사 평가

설문지

바이오컬렉션

피부주름 측정

Laure LE GOFF, PI

Laure LE GOFF

Juliette ROPARS, Dr

Susana QUIJANO-ROY, Pr

Jean-Baptiste DAVION, Dr

Brigitte CHABROL, Pr

Andreea SEFERIAN, Dr

Andreea SEFERIAN

Vincent LAUGEL, Pr

Claude CANCES, Pr

SMN 회복 요법으로 치료받은 척수성 근위축증 환자의 새로운 표현형 특성 분석

Patients receive tazemetostat PO BID on days -1 to 6, and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.

Tazemetostat

Liposome-encapsulated Daunorubicin-Cytarabine

Undergo bone marrow aspiration and biopsy

Bone Marrow Aspiration and Biopsy

Biospecimen Collection

Patients receive palbociclib PO QD on days -3 to -1, then tazemetostat PO twice daily (Days -1 to 6), and CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients also undergo bone marrow aspiration and biopsy and blood sample collection during screening and on study.

Palbociclib

암 환자가 기존 연구에서 계속 치료받도록 돕는 연장 연구로, 다양한 약물 단독 또는 병합 치료를 제공합니다.

Participants will continue to receive Roche IMP(s) monotherapy as per parent protocol, until disease progression, loss of clinical benefit as judged by the investigator, death, withdrawal of study consent, unacceptable toxicity, pregnancy, participants non-compliance, if local access becomes available or study termination by the Sponsor, whichever occurs first.

Ipatasertib will be administered as a monotherapy at the same dose, schedule, and with the same administration guidelines that were in effect at the time of participants discontinuation from the parent study.

Ipatasertib

Atezolizumab will be administered as a monotherapy and in combination at the same dose, schedule, and with the same administration guidelines that were in effect at the time of participants' discontinuation from the parent study.

Atezolizumab

Bevacizumab will be administered as a monotherapy or in combination with atezolizumab at the same dose, schedule, and with the same administration guidelines that were in effect at the time of participants discontinuation from the parent study.

Bevacizumab

Entrectinib will be administered as a monotherapy at the same dose, schedule, and with the same administration guidelines that were in effect at the time of participants discontinuation from the parent study.

Entrectinib

Inavolisib will be administered as a monotherapy or in combination at the same dose, schedule, and with the same administration guidelines that were in effect at the time of participants discontinuation from the parent study.

Inavolisib

Divarasib will be administered as a monotherapy or in combination with atezolizumab or bevacizumab at the same dose, schedule, and with the same administration guidelines that were in effect at the time of participants discontinuation from the parent study.

Divarasib

Participants will continue to receive Roche IMP(s) in combination with other agent(s) as per parent protocol, until disease progression, loss of clinical benefit as judged by the investigator, death, withdrawal of study consent, unacceptable toxicity, pregnancy, participants non-compliance, if local access becomes available or study termination by the Sponsor, whichever occurs first.

Tiragolumab in combination with atezolizumab will be administered at the same dose, schedule, and with the same administration guidelines that were in effect at the time of participants discontinuation from the parent study.

Tiragolumab

Tiragolumab and Atezolizumab in fixed dose combination administered intravenously (IV) at the same dose, schedule, and with the same administration guidelines that were in effect at the time of participants discontinuation from the parent study.

Tiragolumab and Atezolizumab

a 3-week course of ceftriaxone (Rocephin) IV injection (daily dose 2g/day)

+ oral metronidazole (daily dose 1500mg) followed by a 3-week course of oral rifampicin (Rifadin with 10mg/kg/day) + moxifloxacin (Izilox daily dose 400mg) + metronidazole (daily dose 1500mg) followed by a 6-week course of oral rifampicin (Rifadin with 10mg/kg/day) + moxifloxacin (Izilox daily dose 400mg).

A placebo for lymecycline will also be administered during this intensive treatment phase

a 3-week course of ceftriaxone injection + oral metronidazole followed by a 3-week course of oral rifampicin + moxifloxacin +metronidazole followed by a 6-week course of oral rifampicin + moxifloxacin

ROCEPHIN, metronidazole, RIFADIN, IZILOX, placebo combination therapy

12-week course of oral lymecycline (Tetralysal daily dose 452mg) Placebos for all experimental drugs will also be administered during this intensive treatment phase

Lymecyclin and corresponding placebos of the experimental arm

Marie-Aleth Richard, MD, PhD

Maïa Delage-Toriel, MD

Aude Nassif

Anne-Bénédicte Duval-Modeste, Dr

레어노트에 환자 모임 등록

회원 모집 중

비정형 용혈요독증후군 환우·보호자들이 모여있는 오픈 채팅방으로 질환 및 치료에 대한 정보를 공유하고, 일상을 공감합니다.

비정형 용혈요독증후군(aHUS) 카카오톡 오픈채팅방

오픈 채팅방

저인산효소증 환우·보호자들이 모여있는 오픈 채팅방으로 질환 및 치료에 대한 정보를 공유하고, 일상을 공감합니다.

저인산효소증(HPP) 카카오톡 오픈채팅방

진행성 가족성 간내 담즙정체증 환우·보호자들이 모여있는 오픈 채팅방으로 질환 및 치료에 대한 정보를 공유하고, 일상을 공감합니다.

진행성 가족성 간내 담즙정체증(PFIC) 카카오톡 오픈채팅방

발작성 야간혈색소뇨증 환우·보호자들이 모여있는 오픈 채팅방으로 질환 및 치료에 대한 정보를 공유하고, 일상을 공감합니다.

임상시험 현황

근육 기능 평가, 1차 인지 평가, 2차 인지 평가, 심장 평가, MRI, 활동 및 근육 피로 평가, 구근 기능 평가, 체성분 및 대사 평가, 설문지, 생체 수집, 피부주름 측정

타제메토스타트, 리포좀 캡슐화 다우노루비신-시타라빈, 골수 흡인 및 생검, 생체 검체 채취, 팔보시클리브

이파타세르팁, 티라골루맙, 아테졸리주맙, 티라골루맙 및 아테졸리주맙, 베바시주맙, 엔트렉티닙, 이나볼리십, 디바라십

ROCEPHIN, 메트로니다졸, RIFADIN, IZILOX, 위약 병용 요법, Lymecyclin 및 실험군의 해당 위약

환자 모임 정보