A Study of Telitacicept for the Treatment of Generalized Myasthenia Gravis (UPSTREAM MG)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study With an Open-label Extension Period to Evaluate the Efficacy and Safety of Telitacicept in Patients With Generalized Myasthenia Gravis

The purpose of this study is to evaluate the efficacy and safety of telitacicept in the treatment of generalized myasthenia gravis.

Study Overview

• Status: Recruiting
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Drug: Placebo; Biological: Telitacicept

Detailed Description

Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies disrupt the postsynaptic membrane, impairing nerve-to-muscle signal transmission. The predominant manifestation is muscle weakness, which typically worsens with repeated muscle exertion, such that function is usually the best in the morning with more pronounced weakness at the end of the day. A major challenge in MG is the lack of therapies that effectively treat the disease.

Telitacicept is a fully human TACI-Fc fusion protein that targets B-lymphocyte stimulator (BLyS) and A proliferating-inducing ligand (APRIL), neutralizing their interactions with receptors on B cells. The blockage of BLyS and APRIL interaction with their respective cell membrane receptors (transmembrane activator and CAML interactor [TACI], B-cell maturation antigen, and BLyS receptors) by telitacicept can inhibit B-cell proliferation and maturation. This suppression at the proximal portion of the immune response could alleviate autoimmune symptoms.

This is a randomized, double-blind, placebo-controlled Phase 3 study with an open-label extension (OLE) to evaluate the efficacy and safety of telitacicept in a global patient population with gMG. The total duration of the study is variable but will include an approximately 4-week screening period, a 24-week double-blind treatment period (Week 0 through Week 24), a 48-week OLE (Week 24 through Week 72), followed by an extended OLE period (E-OLE), and an 8-week end-of-study follow-up period. The E-OLE is variable duration, defined as the period after the 48-week OLE period until telitacicept is approved for MG in the country or the further development in the indication is concluded.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jeremy Sokolove; Phone Number: 617-655-6580; Email: Study@vorbio.com

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1023AAB
      • Recruiting
      • Stat Research S.A.
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1199ABB
      • Recruiting
      • Hospital Italiano de Buenos Aires
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1221ADC
      • Recruiting
      • Hospital General de Agudos José Maria Ramos Mejía
  • Mendoza Province
    • Mendoza, Mendoza Province, Argentina, M5500AXR
      • Recruiting
      • Fundacion Scherbovsky
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, S2000TP
      • Recruiting
      • INECO Neurociencias Oroño
• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Recruiting
      • Townsville University Hospital
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • Gold Coast University Hospital
• Belgium
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Recruiting
      • Universitair Ziekenhuis (UZ) Leuven - Campus Gasthuisberg
  • Liège
    • Liège, Liège, Belgium, 4000
      • Recruiting
      • Centre Hospitalier Régional de la Citadelle
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 81210-310
      • Recruiting
      • Instituto de Neurologia de Curitiba
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90619-900
      • Recruiting
      • Hospital Sao Lucas Da Pucrs
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083-888
      • Recruiting
      • Universidade Estadual De Campinas
    • Ribeirão Preto, São Paulo, Brazil, 14051-140
      • Recruiting
      • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
    • São Paulo, São Paulo, Brazil, 04038-002
      • Recruiting
      • PSEG Centro de Pesquisa Clinica
• Canada
  • Ontario
    • London, Ontario, Canada, N6C 2R5
      • Recruiting
      • University Hospital - London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • Not yet recruiting
      • Toronto General Hospital
• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Recruiting
      • Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Recruiting
      • Beijing Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400010
      • Recruiting
      • The First Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • Fujian Medical University Union Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Recruiting
      • The Second Hospital & Clinical Medical School. Lan Zhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital, Sun Yat-sen University
  • Guizhou
    • Zunyi, Guizhou, China, 563000
      • Recruiting
      • Affiliated Hospital of Zunyi Medical University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • TongJi Medical College of HUST
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Xiangya Hospital of Central South University
  • Jilin
    • Changchun, Jilin, China, 130000
      • Recruiting
      • Jilin University China-Japan Union Hospital
  • Shaanxi
    • Xi'an, Shaanxi, China, 710000
      • Recruiting
      • The Second Affiliated Hospital of PLA Air Force Military Medical University
    • Xi'an, Shaanxi, China, 710000
      • Recruiting
      • Xi'an Gaoxin Hospital
  • Shangdong
    • Jinan, Shangdong, China, 250000
      • Recruiting
      • Qilu Hospital of Shandong University
    • Jinan, Shangdong, China, 250031
      • Recruiting
      • The 960th Hospital of the Joint Service Support Force of the Chinese People's Liberation Army
    • Jining, Shangdong, China, 272000
      • Recruiting
      • The First People's Hospital of JiNing Medical University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201100
      • Recruiting
      • Huashan Hospital of the ShangHai FuDan University Medical College
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Recruiting
      • First Hospital of Shanxi Medical University
  • Zhejiang
    • Ningbo, Zhejiang, China, 315100
      • Recruiting
      • Ningbo Medical Center Lihuili Hospital
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The 1 School of Medicine, School of Information and Engineering. The 1 Affiliated Hospital of WMU.
• Czechia
  • Moravian-Silesian
    • Ostrava-Poruba, Moravian-Silesian, Czechia, 708 54
      • Recruiting
      • Fakultni Nemocnice Ostrava
  • South Moravian
    • Brno, South Moravian, Czechia, 625 00
      • Recruiting
      • Fakultni nemocnice Brno
    • Brno, South Moravian, Czechia, 603 00
      • Recruiting
      • MINKSneuro s.r.o. - MUDr. Eduard Minks Ph.D.
• France
  • Alpes-Maritimes
    • Nice, Alpes-Maritimes, France, 06001
      • Recruiting
      • Hôpital Pasteur
  • Gironde
    • Bordeaux, Gironde, France, 33076
      • Recruiting
      • Groupe Hospitalier Pellegrin
• Georgia
  • Tbilisi, Georgia, 0114
    • Recruiting
    • Pineo Medical Ecosystem
  • Tbilisi, Georgia, 0160
    • Recruiting
    • Aversi Clinic - Central Branch
  • Tbilisi, Georgia, 0179
    • Recruiting
    • Simon Khechinashvili University Hospital
  • Tbilisi, Georgia, 0114
    • Recruiting
    • Multi-profile Clinic "New Hospitals"
• Italy
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • Recruiting
      • IRCCS Fondazione Casa Sollievo della Sofferenza SG Rotondo
  • Napoli
    • Naples, Napoli, Italy, 80131
      • Recruiting
      • Azienda Ospedaliera Universitaria Federico II
    • Naples, Napoli, Italy, 80131
      • Recruiting
      • Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
    • Naples, Napoli, Italy, 80131
      • Recruiting
      • Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
  • Palermo
    • Cefalù, Palermo, Italy, 90015
      • Recruiting
      • Fondazione Istituto San Raffaele - G. Giglio Di Cefalu
  • Pavia
    • Pavia, Pavia, Italy, 27100
      • Recruiting
      • Istituto Neurologico Casimiro Mondino
  • Rome
    • Rome, Rome, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    • Rome, Rome, Italy, 00189
      • Recruiting
      • Azienda Ospedaliera - Universitaria Sant' Andrea
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 460-0001
      • Recruiting
      • National Hospital Organization - Nagoya Medical Center
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812-8582
      • Recruiting
      • Kyushu University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Recruiting
      • Hokkaido University Hospital
    • Sapporo, Hokkaido, Japan, 060-8543
      • Recruiting
      • Sapporo Medical University Hospital
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0017
      • Recruiting
      • Kobe University Hospital
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • Recruiting
      • St. Marianna University Hospital
    • Yokohama, Kanagawa, Japan, 245-8575
      • Recruiting
      • Yokohama Medical Center
  • Kyoto
    • Kyoto, Kyoto, Japan, 616-8255
      • Recruiting
      • National Hospital Organization Utano National Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 983-8520
      • Recruiting
      • NHO Sendai Medical Center
  • Niigata
    • Kashiwazaki-Shi, Niigata, Japan, 945-8585
      • Recruiting
      • National Hospital Organization Niigata National Hospital
  • Okinawa
    • Ginowan-Shi, Okinawa, Japan, 901-2214
      • Recruiting
      • Okinawa National Hospital
  • Osaka
    • Suita-shi, Osaka, Japan, 564-0013
      • Recruiting
      • Nagoya City University Hospital
  • Sizuoka [Shizuoka]
    • Hamamatsu, Sizuoka [Shizuoka], Japan, 430-8558
      • Recruiting
      • Seirei Hamamatsu General Hospital
  • Tokusima [Tokushima]
    • Tokushima, Tokusima [Tokushima], Japan, 770-8503
      • Recruiting
      • Tokushima University Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Recruiting
      • Juntendo University Hospital
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Recruiting
      • Tokyo Medical University Hospital
• Poland
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 61-853
      • Recruiting
      • Niepubliczny Zakład Opieki Zdrowotnej NEURO - KARD
  • Kuyavian-Pomeranian Voivodeship
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-065
      • Recruiting
      • Medicover Integrated Clinical Services (MICS) - Centrum Medyczne Bydgoszcz
    • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-796
      • Recruiting
      • Neurocentrum Bydgoszcz
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-505
      • Recruiting
      • Krakowska Akademia Neurologii Sp. z o.o.
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-064
      • Recruiting
      • Clinirem - Lublin
  • Lubusz Voivodeship
    • Lublin, Lubusz Voivodeship, Poland, 20-701
      • Recruiting
      • Centrum Medyczne Hope Clinic
    • Nowa Sól, Lubusz Voivodeship, Poland, 67-100
      • Recruiting
      • Twoja Przychodnia Nowosolskie Centrum Medyczne
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 01-684
      • Recruiting
      • Centrum Medyczne Neuroprot
    • Warsaw, Masovian Voivodeship, Poland, 02-172
      • Recruiting
      • MTZ Powered by Pratia
  • Pomeranian Voivodeship
    • Gdansk, Pomeranian Voivodeship, Poland, 80-214
      • Recruiting
      • Uniwersyteckie Centrum Kliniczne w Gdansku
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-123
      • Recruiting
      • Neurologia Śląska Centrum Medyczne
• Spain
  • Alicante
    • Alicante, Alicante, Spain, 03010
      • Recruiting
      • Hospital General Universitario Dr. Balmis
  • Barcelona
    • Barcelona, Barcelona, Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d'Hebron
    • Terrassa, Barcelona, Spain, 08221
      • Recruiting
      • Hospital Universitari Mutua Terrassa
  • Biscay
    • Bilbao, Biscay, Spain, 48013
      • Recruiting
      • Hospital Universitario de Basurto
  • València
    • Valencia, València, Spain, 46026
      • Recruiting
      • Hospital Universitari i Politecnic La Fe
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California
    • Orange, California, United States, 92868
      • Recruiting
      • University of California Irvine
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco (UCSF)
  • Florida
    • Boca Raton, Florida, United States, 33487
      • Recruiting
      • SFM Clinical Research
    • Miami, Florida, United States, 33155
      • Recruiting
      • Allied Biomedical Research Institute (ABRI)
    • Port Charlotte, Florida, United States, 33952
      • Recruiting
      • Medsol Clinical Research Center
    • Tampa, Florida, United States, 33613
      • Recruiting
      • University of South Florida Health (USF Health)
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Wellstar MCG Health Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Recruiting
      • University Of Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville Physicians
  • Massachusetts
    • Foxborough, Massachusetts, United States, 02035
      • Recruiting
      • Neurology Center of New England
      • Contact: Phone Number: 2 781-551-5812; Email: ResearchNCNE@neurocenterne.com
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Recruiting
      • Michigan State University Clinical Center
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Trinity Health - Grand Rapids Hospital
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Health System
    • The Bronx, New York, United States, 10467
      • Recruiting
      • Montefiore Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati Health Physicians - Clifton
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Neurological Institute
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228
      • Recruiting
      • Center for Neurological Disorders, S.C. - Greenfield - Gamma Therapeutic Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Male or female patient aged ≥18 years at screening.
2. Patients have prior confirmed diagnosis of gMG with generalized muscle weakness (typical pattern of weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) clinical classification II-IV.
3. Patients have positive antibodies against AChR or MuSK at screening.
4. MG-ADL score ≥6 points at screening and baseline with ocular-related score <50% of the total score.
5. QMG score ≥8 points, and ≥ 4 items score at least 2 points at screening and baseline.

Key Exclusion Criteria:

1. Patients have been diagnosed with any other autoimmune disease which can potentially pose a safety or efficacy confounding risk.
2. Patients having acute or chronic infection.
3. Patients having thymoma within 5 years or received thymectomy ≤6 months prior to screening. Patients with thymoma diagnosed 3-5 years prior to screening may be eligible if thymoma was at a localized stage and definitively treated with complete surgical resection.
4. Patients having current or history of primary immunodeficiency.
5. Patients having history of malignancy within the last 5 years.
6. Patient having prior or continuing diagnosis of serious cardiovascular, liver, kidney, respiratory system, endocrine or hematologic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Subcutaneous injection
Experimental: Telitacicept	Biological: Telitacicept; Subcutaneous injection; Other Names: RC18; RC18-L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Week 24	The MG-ADL is an 8-item patient-reported outcome measure assessing MG symptoms and their effects on daily activities. Each item in the scale is scored on a 0 to 3 (0=normal, 3=severe disease) point scale. The total score is the sum of all individual item scores ranging from 0 to 24. Higher scores indicate more severe disability due to MG. A decrease from Baseline score indicates improvement.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who achieved minimal symptomatic expression (MSE, defined as having MG-ADL score of 0 or 1) at Week 24	Proportion of patients who achieved minimal symptomatic expression (MSE, defined as having MG-ADL score of 0 or 1) at Week 24	Week 24
Change from baseline in Quantitative Myasthenia Gravis (QMG) score at Week 24	The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consists of 13 items. Each item in the scale is scored on a 0 to 3-point scale, ranging from 0 (no weakness) to 3 (severe weakness), summing up to the overall score range from 0 to 39. Higher scores indicate more severe impairment. A decrease from Baseline score indicates improvement.	Week 24
Change from baseline in MG Quality of Life scale (MG-QOL15r) at Week 24	The MG-QoL15r is a 15-item patient-reported outcome measure designed to assess quality of life in patients with MG. Each item in the scale is scored on a 0 to 2-point scale (0=Not at all, 1=Somewhat, 2=Very much). The total score is the sum of the 15 individual item scores, ranging from 0 to 30. Higher scores indicate more severe impact of the disease on aspects of the patient's life. A decrease from Baseline score indicates improvement.	Week 24
Proportion of patients with a decrease of ≥2 points from baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Week 24	Proportion of patients with a decrease of ≥2 points from baseline in MG-ADL score at Week 24. The MG-ADL is an 8-item patient-reported outcome measure assessing MG symptoms and their effects on daily activities. Each item in the scale is scored on a 0 to 3 (0=normal, 3=severe disease) point scale. The total score is the sum of all individual item scores ranging from 0 to 24. Higher scores indicate more severe disability due to MG.	Week 24
Proportion of patients with a decrease of ≥3 points from baseline in Quantitative Myasthenia Gravis (QMG) score at Week 24	Proportion of patients with a decrease of ≥3 points from baseline in QMG score at Week 24. The QMG is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The scale consists of 13 items. Each item in the scale is scored on a 0 to 3-point scale, ranging from 0 (no weakness) to 3 (severe weakness), summing up to the overall score range from 0 to 39. Higher scores indicate more severe impairment. A decrease from Baseline score indicates improvement.	Week 24

Collaborators and Investigators

• Sponsor: Vor Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: June 7, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Myasthenia Gravis; gMG
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis; telitacicept
• Other Study ID Numbers: RC18G006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No