Efficacy and Safety of M281 in Adults With Warm Autoimmune Hemolytic Anemia
- Registration Number
- NCT04119050
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
The main purpose of this study is to evaluate the efficacy and safety of M281 in participants with warm autoimmune hemolytic anemia (wAIHA).
- Detailed Description
The study consists of a 24-week double-blind, placebo control period, a 144-week open-label extension period and follow-up period of 8 weeks after last study drug administration. Eligible participants will be randomized to placebo or nipocalimab (2 dose levels) during the double-blind period and nipocalimab (2 dose levels) during the open-label extension period.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 111
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description M281 administered every 4 weeks (double-blind period) M281 Participants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period. M281 administered every 4 weeks (double-blind period) Placebo Participants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period. M281 administered every 2 weeks (double-blind period) M281 Participants will receive M281 administered every 2 weeks during the 24 weeks double-blind period. Placebo administered every 2 weeks (double-blind period) Placebo Participants will receive M281 matching placebo administered every 2 weeks during the 24 weeks double-blind period. M281 administered every 4 weeks (open-label extension period) M281 Participants will receive M281 administered every 4 weeks during the 144 weeks open-label extension period. M281 administered every 2 weeks (open-label extension period) M281 Participants will receive M281 administered every 2 weeks during the 144 weeks open-label extension period.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Durable Response of Improvement in Hemoglobin (Hgb) Up to Week 20 of the double-blind period
- Secondary Outcome Measures
Name Time Method Change From Baseline in the Total Score From the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at the Time of Durable Response Baseline (Day 1, Week 0) through Week 24 The FACIT-Fatigue is a self-administered 13-item questionnaire that assess patient-reported fatigue associated with chronic illness therapy. It assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Number of Participants That Simultaneously Attain Normal Lactate Dehydrogenase, Haptoglobin, and Indirect Bilirubin Levels at a Minimum of 3 Consecutive Visits After Baseline Baseline (Day 1, Week 0) through Week 24 Change From Baseline in the Total Score From the FACIT-Fatigue Scale at the end of the Double-blind Period (Week 24) Baseline (Day 1, Week 0) through Week 24 of the double-blind period The FACIT-Fatigue is a self-administered 13-item questionnaire that assess patient-reported fatigue associated with chronic illness therapy. It assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Time to Hgb Response Baseline (Day 1, Week 0) through Week 24 Change from Baseline in Average Daily Dose of Prednisone or Equivalent Baseline (Day 1, Week 0) and at Week 24 Change from baseline in average daily dose of prednisone or equivalent at week 24 among participants on prednisone or equivalent at baseline will be reported.
Change From Baseline in Reticulocyte Count Baseline (Day 1, Week 0) through Week 24 Change From Baseline in Hemolytic Marker - Haptoglobin Baseline (Day 1, Week 0) through Week 24 Percentage of Participants who Experience at Least a 2 g/dL Increase in Hgb From Baseline and Normalization of Lactate Dehydrogenase, Haptoglobin, and Indirect Bilirubin at any Time During the Study Baseline (Day 1, Week 0) through Week 24 Percentage of Participants who Experience at Least a 2 g/dL Increase in Hgb From Baseline and Normalization of Lactate Dehydrogenase, Haptoglobin, and Indirect Bilirubin at 3 Consecutive Visits Baseline (Day 1, Week 0) through Week 24 Percentage of Participants who Achieve the Durable Response in Improvement of Hgb During the Double-blind Period and Maintain that Response for Up to 24 Weeks, Without the Need of Rescue Therapy Up to 24 weeks Percentage of participants who achieve the durable response in improvement of Hgb during the double-blind period and maintain that response for up to 24 weeks, without the need of rescue therapy will be reported.
Change From Baseline in Hemolytic Marker - Lactate Dehydrogenase Baseline (Day 1, Week 0) through Week 24 Mean Time During Which the Primary Endpoint is Maintained Baseline (Day 1, Week 0) through Week 24 Change From Baseline in Hgb Concentration Baseline (Day 1, Week 0) through Week 24 Change From Baseline in Hemolytic Marker - Indirect Bilirubin Baseline (Day 1, Week 0) through Week 24 Change From Baseline in the Total Score, Item Scores, and Impact and Experience Domains From the FACIT-Fatigue Scale Baseline (Day 1, Week 0) through Week 24 of the double-blind period The FACIT-Fatigue scale is a 13-item self-administered questionnaire that assesses both the physical and functional consequences of fatigue. Each question is answered on a 5-point scale, where 0 means "not at all," and 4 means "very much." The FACIT-Fatigue scale score ranges from 0 to 52, with higher scores denoting lower levels of fatigue. A positive change from baseline score indicates an improvement.
Absolute Change from Baseline in Average Daily Dose of Prednisone or Equivalent Baseline (Day 1, Week 0) and at Week 24 Absolute change from baseline in average daily dose of prednisone or equivalent at Week 24 among all participants will be reported.
Change From Baseline in EuroQol 5-dimension 5-level ( EQ-5D-5L) Scale Score Baseline (Day 1, Week 0) through Week 24 The EQ-5D-5L quality of life questionnaire will be used to assess health related quality of life status. The 5 dimensions are mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; each dimension is rated by the patient on a 5 level scale (no problems, slight problems, moderate problems, severe problems, extreme problems).
Hgb Range at Steady State Baseline (Day 1, Week 0) through Week 24 It will be estimated using a model-based longitudinal analysis of Hgb/hemolysis parameters in relationship to IgG level and dose regimen.
Change From Baseline in Medical Outcomes Study Short Form 36 Item Health Survey Version 2 Acute (SF-36v2) Score Baseline (Day 1, Week 0) through Week 24 The SF-36v2 will be used to assess general quality of life. The 36 items on the SF-36 health survey encompass the following 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The 8 domains can be aggregated into 2 summary scales that reflect physical and mental health: a physical component summary (PCS) and a mental component summary (MCS). Responses to all items are rated on a 3-, 5- or 6-point Likert scale. Higher scores indicate a higher level of functioning. A positive change from baseline score indicates an improvement.
Patient-reported Status As Assessed by Patient Global Impression of Change (PGIC) Scale Score At Week 24 The PGIC will assess if there has been an improvement or decline in patient-reported status since the beginning of the treatment. The PGIC is a 7-point response scale. Participants will be asked to rate their current fatigue as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse.
Change From Baseline in Patient Global Impression of Severity (PGIS) Baseline (Day 1, Week 0) through Week 24 The PGIS will be used to assess the severity of warm autoimmune hemolytic anemia (wAIHA) fatigue symptoms. The PGIS is a 5-point response scale. Participant will be asked to rate their fatigue over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe.
Percentage of participants who Achieve Corticosteroid Reduction to less than or equal to (<=) 7.5 milligrams per day (mg/day) of Oral Prednisone (or Equivalent), Among Participants with Prednisone or Equivalent greater than (>) 7.5 mg/day at Baseline At Week 24 Percentage of participants who achieve corticosteroid reduction to \<= 7.5 mg/day of oral prednisone (or equivalent) at Week 24 of the double-blind period, among participants with prednisone or equivalent \>7.5 mg/day at baseline will be reported.
Trial Locations
- Locations (171)
Jiangsu Province Hospital
🇨🇳Nanjing, China
Affiliated Hospital of Nantong University
🇨🇳Nantong, China
Shanghai Zhongshan Hospital
🇨🇳ShangHai, China
Huashan Hospital affiliated to Fudan University
🇨🇳Shanghai, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, China
Hosp. Virgen Del Rocio
🇪🇸Málaga, Spain
Hosp. Son Llatzer
🇪🇸Palma de Mallorca, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
MemorialCare Medical Group
🇺🇸Fountain Valley, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Compassionate Cancer Care
🇺🇸Riverside, California, United States
American Institute of Research
🇺🇸Whittier, California, United States
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
GNP Research
🇺🇸Cooper City, Florida, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
21st Century Oncology
🇺🇸Jacksonville, Florida, United States
Lakes Research
🇺🇸Miami Lakes, Florida, United States
AdventHealth Cancer Institute
🇺🇸Orlando, Florida, United States
Children's Research Institute
🇺🇸Saint Petersburg, Florida, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Alliance for Multispeciality Research
🇺🇸Merriam, Kansas, United States
Tulane University School of Medicine
🇺🇸New Orleans, Louisiana, United States
Henry Ford Medical Center
🇺🇸Detroit, Michigan, United States
Research Medical Center
🇺🇸Kansas City, Missouri, United States
Montefiore Medical Center
🇺🇸Lake Success, New York, United States
Monter Cancer Center
🇺🇸Lake Success, New York, United States
Hematology Oncology Associates of Rockland
🇺🇸Nyack, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Taussig Cancer Insititute Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
The Ohio State University- James Cancer Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
West Penn Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States
Northwest Medical Specialists
🇺🇸Tacoma, Washington, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Hospital das Clínicas da Faculdade de Medicina de Botucatu
🇧🇷Botucatu, Brazil
Impar Servicos Hospitalares S/A - Hospital Brasilia
🇧🇷Brasilia, Brazil
CTO Centro de Tratamento Oncologico Unidade Belem
🇧🇷Campinas, Brazil
Hospital Das Clinicas Da Universidade Federal De Goias
🇧🇷Goiânia, Brazil
Complexo Hospitalar de Niteroi
🇧🇷Niterói, Brazil
Oncoclinicas - Unidade OC Oncoclinicas Multihemo Ilha do Leite
🇧🇷Recife, Brazil
Nucleo de Oncologia da Bahia
🇧🇷Salvador, Brazil
Hospital Sao Rafael
🇧🇷Salvador, Brazil
CEPHO Centro de Estudos e Pesquisa de Hematologia e Oncologia
🇧🇷Santo Andre, Brazil
Hospital Santa Marcelina
🇧🇷Santo Andre, Brazil
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base
🇧🇷Sao Jose Do Rio Preto, Brazil
Sociedade Beneficente de Senhoras Hospital Sirio Libanes
🇧🇷Sao Paulo, Brazil
Universidade Federal de Sao Paulo
🇧🇷Sao Paulo, Brazil
Hospital Das Clinicas Da Faculdade De Medicina Da USP
🇧🇷Sao Paulo, Brazil
Beijing Chao-yang Hospital, Capital Medical University
🇨🇳Beijing Shi, China
Peking University People s Hospital
🇨🇳Beijing Shi, China
The First Hospital of Jilin University
🇨🇳Changchun, China
West China Hospital of Sichuan University
🇨🇳Chengdu, China
Guangzhou First Municipal People's Hospital
🇨🇳Guangzhou Shi, China
Hainan General Hospital
🇨🇳Haikou, China
First Affiliated Hospital Medical School of Zhejiang University
🇨🇳Hangzhou, China
Lanzhou University Second Hospital
🇨🇳Lanzhou, China
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, China
The First Affiliated Hospital of Xian Jiaotong University
🇨🇳Xi'An, China
Fakultni nemocnice Brno
🇨🇿Brno, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Ustav Hematologie A Krevni Transfuze
🇨🇿Praha 2, Czechia
Alexandria University Hospital
🇪🇬Alexandria, Egypt
Cairo university
🇪🇬Cairo, Egypt
Ain Shams University Hospital
🇪🇬Cairo, Egypt
National Cancer Institute
🇪🇬Cairo, Egypt
Nasser institute Hospital
🇪🇬Cairo, Egypt
Mansoura University Hospital
🇪🇬Mansoura, Egypt
ICH Hopital A. Morvan
🇫🇷Brest Cedex 2, France
CHU Dijon Bourgogne
🇫🇷Dijon, France
CHU Grenoble
🇫🇷La Tronche, France
CHU Nantes - Hotel Dieu
🇫🇷Nantes, France
CHU De Poitiers
🇫🇷Poitiers, France
CHRU Hopital Sud
🇫🇷Rennes, France
Onkologische Schwerpunktpraxis
🇩🇪Berlin, Germany
Universitatsklinikum Essen
🇩🇪Essen, Germany
Rotkreuzklinikum München
🇩🇪München, Germany
General Hospital of Athens G Gennimatas
🇬🇷Athens, Greece
Laiko General Hospital of Athens
🇬🇷Athens, Greece
Attikon University General Hospital of Attica
🇬🇷Athens, Greece
University Hospital Of Larissa
🇬🇷Larissa, Greece
University General Hospital of Rio Patras
🇬🇷Patras, Greece
University General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Del Pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet Szent Laszlo Telephely
🇭🇺Budapest, Hungary
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Petz Aladar Megyei Oktato Korhaz
🇭🇺Gyõr, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
🇭🇺Kaposvar, Hungary
Ha'Emek Medical Center
🇮🇱Afula, Israel
Soroka Medical Center
🇮🇱Beer Sheva, Israel
Rambam Health Care Campus
🇮🇱Haifa, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Hospital Sanz Medical Center Laniado Hospital
🇮🇱Kiryat Tzanz, Israel
Rabin Medical Center, Beilinson Hospital
🇮🇱Petach Tikvah, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
PO C e G Mazzoni AST Ascoli Piceno
🇮🇹Ascoli Piceno, Italy
ASST Spedali Civili di Brescia
🇮🇹Brescia, Italy
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi
🇮🇹Catania, Italy
AOU Policlinico G Rodolico S Marco
🇮🇹Catania, Italy
Azienda Ospedaliero Universitaria Careggi
🇮🇹Firenze, Italy
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
Fondazione IRCCS San Gerardo dei Tintori
🇮🇹Monza, Italy
Azienda Ospedaliero Universitaria Maggiore della Carita di Novara
🇮🇹Novara, Italy
Umberto I Policlinico di Roma
🇮🇹Roma, Italy
Fondazione Policlinico Universitario A Gemelli IRCCS
🇮🇹Roma, Italy
Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Azienda Ulss 8 Berica- Ospedale Di Vicenza
🇮🇹Vicenza, Italy
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Saitama Medical University Hospital
🇯🇵Iruma-gun, Japan
St Marianna University Hospital
🇯🇵Kanagawa, Japan
Japan Community Health care Organization Kyushu Hospital
🇯🇵Kitakyusyu-Shi, Japan
Yamanashi Prefectural Central Hospital
🇯🇵Kofu-Shi, Japan
Ogaki Municipal Hospital
🇯🇵Ogaki, Japan
Sapporo Medical University Hospital
🇯🇵Sapporo, Japan
Tohoku University Hospital
🇯🇵Sendai, Japan
Osaka University Hospital
🇯🇵Suita, Japan
Toyama Prefectural Central Hospital
🇯🇵Toyama, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan
Tottori University Hospital
🇯🇵Yonago, Japan
Hosp Virgen de La Victoria
🇪🇸Málaga, Spain
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Ampang
🇲🇾Ampang, Malaysia
Hospital Sultanah Aminah
🇲🇾Johor Bahru, Malaysia
Hospital Queen Elizabeth
🇲🇾Kota Kinabalu, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Malaysia
Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
Sunway Medical Centre
🇲🇾Petaling Jaya, Malaysia
Amsterdam Universitair Medische Centra Locatie Vrije Universiteit Medisch Centrum
🇳🇱Amsterdam, Netherlands
Academic Medical Centre Amsterdam
🇳🇱Amsterdam, Netherlands
Maastricht Universitair Medisch Centrum
🇳🇱Maastricht, Netherlands
Interhem
🇵🇱Bialystok, Poland
Klinika Hematologii i Transplantologii, UCK
🇵🇱Gdansk, Poland
Pratia Onkologia Katowice
🇵🇱Katowice, Poland
Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im M Kopernika w Lodzi
🇵🇱Lodz, Poland
Szpital Wojewodzki w Opolu
🇵🇱Opole, Poland
MTZ Clinical Research Powered by Pratia
🇵🇱Warszawa, Poland
Hosp. Univ. Principe de Asturias
🇪🇸Alcalá de Henares, Spain
Hosp. Univ. Germans Trias I Pujol
🇪🇸Badalona, Spain
Hosp Clinic de Barcelona
🇪🇸Barcelona, Spain
Complejo Asistencial Univ. de Burgos
🇪🇸Burgos, Spain
Hosp Reina Sofia
🇪🇸Córdoba, Spain
Hosp. Univ. de Gran Canaria Dr. Negrin
🇪🇸Las Palmas de Gran Canaria, Spain
Hosp. Univ. Infanta Leonor
🇪🇸Madrid, Spain
Hosp. Univ. Ramon Y Cajal
🇪🇸Madrid, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hosp. Univ. 12 de Octubre
🇪🇸Madrid, Spain
Hosp. Univ. La Paz
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Spain
Hosp Regional Univ de Malaga
🇪🇸Málaga, Spain
Hosp. Quiron Madrid Pozuelo
🇪🇸Pozuelo de Alarcon, Spain
Hosp. Univ. I Politecni La Fe
🇪🇸Valencia, Spain
Hosp. Univ. Miguel Servet
🇪🇸Zaragoza, Spain
Cherkassy Regional Oncology Dispensary, Department of Hematology
🇺🇦Cherkassy, Ukraine
Dnipropetrovsk State Medical Academy, Dnipropetrovsk City Multifield Clinical Hospital # 4
🇺🇦Dnipro, Ukraine
Medical Center 'Ok Clinic' of LLC 'International Institute of Clinical Studies'
🇺🇦Kyiv, Ukraine
Kyiv City Clinical Hospital #9, Department of infectious diseases
🇺🇦Kyiv, Ukraine
Ternopil University Hospital of Ternopil Regional Council
🇺🇦Ternopil, Ukraine
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
Liverpool University Hospitals NHS Foundation Trust
🇬🇧Liverpool, United Kingdom
Barts Health NHS Trust
🇬🇧London, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, United Kingdom
University Hospitals Plymouth NHS Trust
🇬🇧Plymouth, United Kingdom
University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom