망막 질환을 가진 환자에게 주사한 치료제의 장기 안전성과 효과를 비교하는 시험입니다.

Participants previously treated with sub-retinal injection of BIIB111 in antecedent studies 273CH301 (NCT03496012) and 273CH203 (NCT03507686) will be enrolled. Participants previously treated with this same sub-retinal injection (rAAV2-REP1) in antecedent studies 20150371 (NCT02553135), Pro00028599 (NCT02077361), THOR-TUE-01 (NCT02671539), CHM09/01 (NCT01461213) and REGEN2015 (NCT02407678) will also be invited for enrollment. This is a follow-up study, investigational product was administered in the previous study.

Administered as specified in the treatment arm.

BIIB111

Participants previously treated with sub-retinal injection of BIIB112 in the antecedent study 274RP101 (NCT03116113) will be enrolled. This is a follow-up study, investigational product was administered in the previous study.

BIIB112

Untreated participants who served as controls in the antecedent study 273CH301 (NCT03496012), investigating treatment with BIIB111, will be enrolled. This is a follow-up study, participants will not be administered study medication nor receive a sham surgery.

선행 연구 273CH301(NCT03496012) 및 273CH203(NCT03507686)에서 BIIB111의 망막하 주사 치료를 받은 참가자가 등록될 예정입니다. 선행 연구 20150371(NCT02553135), Pro00028599(NCT02077361), THOR-TUE-01(NCT02671539), CHM09/01(NCT01461213) 및 REGEN2015(NCT02407678)에서 동일한 망막하 주사(rAAV2-REP1) 치료를 받은 참가자도 등록될 예정입니다. 본 연구는 후속 연구이며, 연구용 의약품은 이전 연구에서 투여되었습니다.

선행 연구 274RP101(NCT03116113)에서 BIIB112의 망막하 주사 치료를 받은 참가자가 등록될 예정입니다. 본 연구는 후속 연구이며, 연구용 의약품은 이전 연구에서 투여되었습니다.

BIIB111 치료를 조사하는 선행 연구 273CH301(NCT03496012)에서 대조군으로 참여했던 미치료 참여자가 등록될 예정입니다. 본 연구는 추적 연구이며, 참여자에게는 연구 약물이 투여되지 않으며, 가짜 수술도 시행되지 않습니다.

맥락막변성증 치료를 위한 BIIB111과 X연관성 색소성 망막염 치료를 위한 BIIB112의 장기 안전성 및 효능 추적 조사

ALS 환자 12명을 대상으로 QRL-101 단일 용량의 안전성과 체내 반응을 보는 초기 시험입니다.

Single doses of QRL-101 will be orally administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.

QRL-101

Single doses of comparator placebo will be orally administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.

Single doses of compartor placebo will be orally administered. The dose levels may change subject to available nonclinical, clinical, safety, and PK data.

Placebo

QRL-101은 단회 투여되며, 경구 투여됩니다. 투여량은 비임상, 임상, 안전성 및 약동학(PK) 자료에 따라 변경될 수 있습니다.

비교 대상 위약은 단회 투여됩니다. 투여량은 비임상, 임상, 안전성 및 약동학(PK) 자료에 따라 변경될 수 있습니다.

위약

ALS 성인 환자에서 QRL-101의 PK/PD 관계를 탐구하는 연구

2세 이상 18세 미만 척수성 근위축증 환자에게 새로운 주사 치료의 효과와 안전성을 15개월 동안 평가하는 시험입니다.

OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg).

OAV101

A skin prick in the lumbar region without any medication.

The sham procedure will consist of a small needle prick on the lower back at the location where the LP injection is normally made. The needle will break the skin, but no needle insertion for lumbar puncture will occur.

Sham control

OAV101은 1.2 x 10\^14 벡터 게놈(vg)의 단일, 일회성 척추강 내 투여량으로 투여됩니다.

약물을 사용하지 않고 요추 부위의 피부를 찌르는 시술입니다.

가짜 통제

2형 척수성 근위축증(SMA) 소아 환자에서 척수강 내 OAV101(AVXS-101)의 효능 및 안전성

Weeks 1-3\* patients receive either (a) Neratinib, (b) Letrozole or Anastrozole or (c) Neratinib + Letrozole or Anastrozole

Weeks 4-24 patients receive Neratinib + Letrozole or Anastrozole and Trastuzumab

\*Starting drug intervention varies for the first 3 weeks depending on arms: a, b, and c by randomization.

120mg for 7 days; 160mg for 7 days ; 240mg for 7 days. 240 mg (up to a maximum of 24 weeks) orally daily\*.

Neratinib

L: (2.5 mg) OR A: (1 mg) orally daily (up to a maximum of 24 weeks)\*

Letrozole (L) or Anastrozole (A)

All Arms 8mg/kg loading dose followed by 6mg/kg every 3 weeks administered every 3 weeks by IV starting wk 4. Trastuzumab biosimilars may be used per institutional guidelines.

Trastuzumab

Oana Danciu, MD

Lisa Carrozzi, OCN

Kathleen Pratt

Ruth O'Regan, MD

Cindy Brown

Monali Vasekar, MD

UW Cancer Connect

Kari Wisinski, MD

Patients with EGFR-mutant advanced non-small cell lung cancer who achieve disease control after first-line osimertinib plus chemotherapy (FLAURA2 regimen) will receive local therapy (surgery or radiotherapy) to the primary tumor. The study will evaluate clinical outcomes including progression-free survival, overall survival, and treatment-related toxicity.

Patients will receive local therapy, either surgical resection or radiotherapy, to the primary lung tumor following disease control after first-line treatment with osimertinib plus platinum-based chemotherapy (FLAURA2 regimen). The specific modality (surgery or radiotherapy) will be determined based on tumor characteristics, patient condition, and multidisciplinary team assessment.

Local Therapy (Surgery or Radiotherapy)

Subjects randomized into Group 1 will be provided with a sleep schedule each week based on an algorithm (Algorithm 1) calculated from sleep diaries and fitbit data. Subjects will complete questionnaires at an initial clinic visit. Subjects will then complete a sleep diary upon waking each day and wear a Fitbit Charge 2 device for sleep monitoring each day for 8 weeks. At the end of the study, subjects will complete follow-up questionnaires at a final clinic visit.

A sleep extension algorithm (algorithm 1) will be calculated and implemented based on information obtained from Sleep Diary and Fitbit data.

Algorithm 1

Subjects randomized into Group 2 will be provided with a sleep schedule each week based on an algorithm (Algorithm 2) calculated from sleep diaries and fitbit data. Subjects will complete questionnaires at an initial clinic visit. Subjects will then complete a sleep diary upon waking each day and wear a Fitbit Charge 2 device for sleep monitoring each day for 8 weeks. At the end of the study, subjects will complete follow-up questionnaires at a final clinic visit.

A sleep extension algorithm (algorithm 2) will be calculated and implemented based on information obtained from Sleep Diary and Fitbit data.

Algorithm 2

Subjects randomized into Group 1 will be provided with a sleep schedule each week based on an algorithm (Algorithm 3) calculated from sleep diaries and fitbit data. Subjects will complete questionnaires at an initial clinic visit. Subjects will then complete a sleep diary upon waking each day and wear a Fitbit Charge 2 device for sleep monitoring each day for 8 weeks. At the end of the study, subjects will complete follow-up questionnaires at a final clinic visit.

A sleep extension algorithm (algorithm 3) will be calculated and implemented based on information obtained from Sleep Diary and Fitbit data.

Algorithm 3

Participants will receive placebo PO dosed once daily

Participants will receive REC-4881 4mg PO dosed once daily

REC-4881

Participants will receive REC-4881 8mg PO dosed once daily

Rachel Gross

James Ogilvie, MD

Lauren Hegelson

Lisa Boardman, MD

Asima Badic

Paul Wise, MD

Sophia Caterina

Bryson Katona, MD

Casey Koza

Reid Ness, MD

Yaemi Cheng

Luke Engelking, MD

Diane Weber

Eduardo Vilar-Sanchez, MD

Tavia Dutson

Jessica Stout, MD

Brooke Grubb

Emily Chesterfield

Gautam Mankaney, MD

Participants will receive 400 mg/day of TTI-101 twice daily (BID) for 12 weeks.

TTI-101

Participants will receive 800 mg/day of TTI-101 BID for 12 weeks.

Participants will receive a matching placebo BID for 12 weeks.

Participants will receive BIIB091 high dose and matching placebo for DRF, orally, for up to 48 weeks.

BIIB091

Participants will receive BIIB091 low dose and matching placebo for DRF, orally, for up to 48 weeks.

Participants will receive DRF standard dose and matching placebo for BIIB091, orally, for up to 48 weeks.

Participants will receive selected dose of BIIB091 (based on Part 1 data) and DRF standard dose, orally, for up to 48 weeks.

Participants will receive selected dose of BIIB091 (based on Part 1 data) and DRF low dose, orally, for up to 48 weeks.

Hristo Lilovski

Maya Danovska-Mladenova

Georgi Slavov

Ivan Gospodinov Milanov

Dimitar Maslarov

Ivan Staikov

Rosen Ikonomov

Penko Minkov Shotekov

Krasimir Genov

Michal Dufek

Zbysek Pavelek

Ondrej Skoda

Marketa Grunermelova

Marta Vachova

Felix Bischof

Patrick Oschmann

Klaus Lehmann-Horn

Sven Meuth

Eugen Schlegel

Tjalf Ziemssen

Diego Centonze

Luigi Grimaldi

Maria Matilde Inglese

Antonio Gallo

Elena Colombo

Girolama A. Marfia

Antonella Conte

Waldemar Fryze

Marta Bilik

Aleksandra Porosinska

Maciej Maciejowski

Tomasz Jerzy Zielinski

Elzbieta Jasinska

Agnieszka Slowik

Krzysztof Selmaj

Magdalena Boczarska-Jedynak

Karolina Piasecka-Stryczynska

Jan Ilkowski

Iwona Rosciszewska Zukowska

Maciej Czarnecki

Monika Adamczyk Sowa

Angel R Chinea Martinez

Simona Petrescu

Dan Mitrea

Emilian Silviu Manescu

Rafael Arroyo Gonzalez

Jose Eustasio Meca Lallana

Jose Enrique Martinez Rodriguez

Eduardo A. Morales

Lucienne Costa Frossard Franca

Ana Maria Alonso Torres

Chiara Zecca

Robert Hoepner

Patrick Roth

Suraj A. Muley

Joanna A. Cooper

Michael Sy

Enrique Alvarez

Silvia Rosa Delgado

Derrick Scott Robertson

Stuart James Shafer

Ajay Gupta

Sharon G. Lynch

Daniel Becker

Robert T. Naismith

Mary Ann Picone

Clotilde Hainline

Mark Gudesblatt

Nuhad Abou Zeid

Lawrence Phillip Goldstick

Devon Scott Conway

Aaron L. Boster

Lee S. Stein

Siddharama S Pawate

Tania Reyna

Christopher C. Luzzio

Ahmed Zayed Obeidat

Sevasemten is administered orally once per day

Sevasemten Dose 1

Placebo is administered orally once per day

Sevasemten Dose 2

Sevasemten Dose 3

AP01

Systemic SHR-A1811 therapy combined with intrathecal SHR-A1811 therapy

Systemic therapy: 4.8 mg/kg administered as an intravenous infusion on Day 1 of each cycle. 3 weeks a cycle. Continuous medication until study completion, occurrence of intolerable toxicity, disease progression, withdrawal from the study for any reason, or death, whichever occurs first, or until the investigator deems that the patient would no longer benefit from the treatment.

SHR-A1811

Intrathecal therapy: Administered intrathecally on Day 1 of each cycle. Dose escalation follows a Bayesian Optimal Interval (BOIN) design with three predefined dose levels-15 mg, 30 mg, and 40 mg. The starting dose level is 15 mg. Patients are enrolled in cohorts of three per dose level. If no dose-limiting toxicities (DLTs) are observed, escalation proceeds to the next higher dose level according to the BOIN algorithm. Treatment is administered for a minimum of two cycles and is continued until cerebrospinal fluid (CSF) cytology achieves negative conversion, completion of six cycles, or intolerable adverse events, whichever occurs first. Extension beyond six cycles may be permitted following investigator's discussion and must be documented with justification.

Systemic SHR-A1811 therapy combined with radiotherapy

radiotherapy is determined by investigator's choice

radiotherapy

Peking University Cancer Hospital & Institute

CC-95251

Azacitidine

Venetoclax

Cisplatin/capecitabine or cisplatin/5-fluorouracil

Cisplatin

5-fluorouracil or Capecitabine

gastrectomy

Cisplatin/capecitabine plus trastuzumab or cisplatin/5-fluorouracil plus trastuzumab

cisplatin/capecitabine plus trastuzumab and pertuzumab or cisplatin/5-fluorouracil plus trastuzumab and pertuzumab

Pertuzumab

European Organisation for Research and Treatment of Cancer - EORTC

During Part 1 (Dose Confirmation Phase), participants with SLE will undergo lymphodepleting chemotherapy (LDC) followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental human recombinant interleukin 2 (IL-2).

After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.

During Part 2 (Dose Expansion Phase), participants will receive treatments using the recommended phase 2 regimen (RP2R) confirmed during Part 1.

CNTY-101 cells for intravenous (IV) infusion

CNTY-101

IL-2

Lymphodepleting Chemotherapy

During Part 1 (Dose Confirmation Phase), participants with LN will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.

After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.

During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.

During Part 1 (Dose Confirmation Phase), participants with IIM will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.

After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.

During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.

During Part 1 (Dose Confirmation Phase), participants with DcSSC will undergo LDC followed by administration of CNTY-101, administered 3 times over 3 weeks, during Cycle 1 (cycle length = 28 days), alone or with supplemental IL-2.

After completion of Cycle 1, CNTY-101 (without preceding LDC), will be administered 3 times over 3 weeks, during Cycle 2 (cycle length = 28 days), alone or with supplemental IL-2.

During Part 2 (Dose Expansion Phase), participants will receive treatments using the RP2R confirmed during Part 1.

맥락막변성증 치료를 위한 BIIB111과 X연관성 색소성 망막염 치료를 위한 BIIB112의 장기 안전성 및 효능 추적 조사

ALS 성인 환자에서 QRL-101의 PK/PD 관계를 탐구하는 연구

2형 척수성 근위축증(SMA) 소아 환자에서 척수강 내 OAV101(AVXS-101)의 효능 및 안전성

네라티닙, 레트로졸(L) 또는 아나스트로졸(A), 트라스투주맙

국소 치료(수술 또는 방사선 치료)

알고리즘 1, 알고리즘 2, 알고리즘 3

REC-4881, 위약

TTI-101, 위약

BIIB091, DRF, 위약

세바셈텐 1회 복용량, 세바셈텐 2회 복용량, 세바셈텐 3회 복용량, 위약

AP01, 위약

SHR-A1811, SHR-A1811, 방사선 치료

CC-95251, 아자시티딘, 베네토클락스

시스플라틴, 5-플루오로우라실 또는 카페시타빈, 트라스투주맙, 페르투주맙, 위절제술

CNTY-101, IL-2, 림프구 감소 화학 요법

SAR408701, 라무시루맙, 펨브롤리주맙

EO-3021, 라무시루맙(CYRAMZA®), 도스타리맙

FOLFOX4, Adebrelimab, Apatinib, Icaritin, SHR-1701, QL1706, Bevacizumab, HAIC, 국소 치료, 원래 치료 요법

AZD0901, 5-플루오로우라실, 류코보린, l-류코보린, 이리노테칸, 나노리포좀 이리노테칸, 젬시타빈

TAK-881, 하이크비아