Efficacy and Safety of M281 in Adults With Warm Autoimmune Hemolytic Anemia

Warm Autoimmune Hemolytic Anemia Clinical Trial

Official title:

Efficacy and Safety of M281 in Adults With Warm Autoimmune Hemolytic Anemia: A Multicenter, Randomized, Double-blind, Placebo-controlled Study With a Long-term Open-label Extension

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04119050
• Other study ID #: CR108987
• Secondary ID: 2019-000720-17MO
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 15, 2019
• Est. completion date: April 10, 2028

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the efficacy and safety of M281 in participants with warm autoimmune hemolytic anemia (wAIHA).

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 information / eligibility

• Status: Recruiting
• Enrollment: 111
• Est. completion date: April 10, 2028
• Est. primary completion date: March 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Participants greater than or equal to (>=)18 years of age
• Have been diagnosed with warm autoimmune hemolytic anemia (wAIHA) for at least 3 months, and are currently receiving treatment for wAIHA or have previously received treatment for wAIHA (treatment-naive participants are not eligible)
• Participants must be able to understand and voluntarily provide written informed consent to participate in the study and comply with all study procedures

Exclusion criteria:

• Participants must not be pregnant or breastfeeding
• Participants must not have other clinically relevant abnormalities currently or in their history that the Investigator would deem them ineligible to participate
• Have been diagnosed with cold antibody autoimmune hemolytic anemia (AIHA), cold agglutinin syndrome, mixed type (that is, warm and cold) AIHA, or paroxysmal cold hemoglobinuria

Related Conditions & MeSH terms

• Anemia
• Anemia, Hemolytic
• Anemia, Hemolytic, Autoimmune
• Hemolysis
• Warm Autoimmune Hemolytic Anemia

Intervention

Drug:
• M281
M281 injection administered as intravenous infusion
• Placebo
Placebo administered as intravenous infusion

Locations

Country	Name	City	State
Brazil	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	Hospital Sao Rafael	Salvador
Brazil	Nucleo de Oncologia da Bahia	Salvador
Brazil	Hospital Santa Marcelina	Santo Andre
Brazil	CEPHO - Centro de Estudos e Pesquisa de Hematologia e Oncologia	Santo André
Brazil	Centro Integrado de Pesquisa -Hospital de Base de São José do Rio Preto	Sao Jose Do Rio Preto
Brazil	Hospital Das Clinicas Da Faculdade De Medicina Da USP	Sao Paulo
Brazil	Hospital Sirio Libanes Sao Paulo	Sao Paulo
China	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	Jiangsu Province Hospital	Nanjing
China	Affiliated Hospital of Nantong University	Nantong
China	Huashan Hospital affiliated to Fudan University	Shanghai
China	Shanghai Zhongshan Hospital	ShangHai
China	The First Affiliated Hospital of Soochow University	Suzhou
China	Tianjin Medical University General Hospital	Tianjin
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
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Ustav Hematologie A Krevni Transfuze	Praha 2
Egypt	Alexandria University Hospital	Alexandria
Egypt	Ain Shams University Hospital	Cairo
Egypt	Cairo university	Cairo
Egypt	Nasser institute Hospital	Cairo
Egypt	National Cancer Institute	Cairo
Egypt	Mansoura University Hospital	Mansoura
France	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
Germany	Onkologische Schwerpunktpraxis	Berlin
Germany	Universitatsklinikum Essen	Essen
Germany	Rotkreuzklinikum München	München
Greece	Attikon University General Hospital of Attica	Athens
Greece	General Hospital of Athens 'G. Gennimatas'	Athens
Greece	Laiko General Hospital of Athens	Athens
Greece	University Hospital Of Larissa	Larissa
Greece	University General Hospital of Rio Patras	Patras
Greece	University General Hospital of Thessaloniki	Thessaloniki
Hungary	Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet, Szent László Telephely	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyõr
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz	Kaposvar
Israel	Ha'Emek Medical Center	Afula
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare Zedek 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
Italy	PO C e G Mazzoni AST Ascoli Piceno	Ascoli Piceno
Italy	ASST Spedali Civili di Brescia	Brescia
Italy	AOU Policlinico G Rodolico S Marco	Catania
Italy	Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi	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	Fondazione Policlinico Universitario A Gemelli IRCCS	Roma
Italy	Umberto I Policlinico di Roma	Roma
Italy	Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino	Torino
Italy	Azienda Ulss 8 Berica- Ospedale Di Vicenza	Vicenza
Japan	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
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Malaysia	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
Netherlands	Academic Medical Centre Amsterdam	Amsterdam
Netherlands	Amsterdam Universitair Medische Centra Locatie Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Maastricht Universitair Medisch Centrum	Maastricht
Poland	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	Lódz
Poland	Szpital Wojewodzki w Opolu	Opole
Poland	MTZ Clinical Research Powered by Pratia	Warszawa
Spain	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. 12 de Octubre	Madrid
Spain	Hosp. Univ. Infanta Leonor	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Ramon Y Cajal	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Hosp. Regional Univ. de Malaga	Málaga
Spain	Hosp. Virgen de La Victoria	Málaga
Spain	Hosp. Virgen Del Rocio	Málaga
Spain	Hosp. Son Llatzer	Palma de Mallorca
Spain	Clinica Univ. de Navarra	Pamplona
Spain	Hosp. Quiron Madrid Pozuelo	Pozuelo de Alarcon
Spain	Hosp. Univ. I Politecni La Fe	Valencia
Spain	Hosp. Univ. Miguel Servet	Zaragoza
Ukraine	Cherkassy Regional Oncology Dispensary, Department of Hematology	Cherkassy
Ukraine	Dnipropetrovsk State Medical Academy, Dnipropetrovsk City Multifield Clinical Hospital # 4	Dnipro
Ukraine	Kyiv City Clinical Hospital #9, Department of infectious diseases	Kyiv
Ukraine	Medical Center 'Ok Clinic' of LLC 'International Institute of Clinical Studies'	Kyiv
Ukraine	Ternopil University Hospital of Ternopil Regional Council	Ternopil
United Kingdom	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 States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Rush University Medical Center	Chicago	Illinois
United States	Taussig Cancer Insititute - Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University- James Cancer Hospital	Columbus	Ohio
United States	GNP Research	Cooper City	Florida
United States	Henry Ford Medical Center	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	MemorialCare Medical Group	Fountain Valley	California
United States	University of Florida College of Medicine	Gainesville	Florida
United States	East Carolina University	Greenville	North Carolina
United States	21st Century Oncology	Jacksonville	Florida
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	University of Southern California	Los Angeles	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Alliance for Multispeciality Research	Merriam	Kansas
United States	Lakes Research	Miami Lakes	Florida
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Hematology Oncology Associates of Rockland	Nyack	New York
United States	AdventHealth Cancer Institute	Orlando	Florida
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	Compassionate Cancer Care	Riverside	California
United States	Children's Research Institute	Saint Petersburg	Florida
United States	University of Utah	Salt Lake City	Utah
United States	Northwest Medical Specialists	Tacoma	Washington
United States	American Institute of Research	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Brazil,  China,  Czechia,  Egypt,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Poland,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving Durable Response of Improvement in Hemoglobin (Hgb)		Up to Week 20 of the double-blind period
Secondary	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	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.	Baseline (Day 1, Week 0) through Week 24
Secondary	Change From Baseline in the Total Score From the FACIT-Fatigue Scale at the end of the Double-blind Period (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.	Baseline (Day 1, Week 0) through Week 24 of the double-blind period
Secondary	Change from Baseline in Average Daily Dose of Prednisone or Equivalent	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.	Baseline (Day 1, Week 0) and at Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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	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.	Up to 24 weeks
Secondary	Change From Baseline in Hgb Concentration		Baseline (Day 1, Week 0) through Week 24
Secondary	Change From Baseline in Reticulocyte Count		Baseline (Day 1, Week 0) through Week 24
Secondary	Change From Baseline in Hemolytic Marker - Lactate Dehydrogenase		Baseline (Day 1, Week 0) through Week 24
Secondary	Change From Baseline in Hemolytic Marker - Haptoglobin		Baseline (Day 1, Week 0) through Week 24
Secondary	Change From Baseline in Hemolytic Marker - Indirect Bilirubin		Baseline (Day 1, Week 0) through Week 24
Secondary	Time to Hgb Response		Baseline (Day 1, Week 0) through Week 24
Secondary	Mean Time During Which the Primary Endpoint is Maintained		Baseline (Day 1, Week 0) through Week 24
Secondary	Change From Baseline in the Total Score, Item Scores, and Impact and Experience Domains From the FACIT-Fatigue Scale	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.	Baseline (Day 1, Week 0) through Week 24 of the double-blind period
Secondary	Change From Baseline in EuroQol 5-dimension 5-level ( EQ-5D-5L) Scale Score	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).	Baseline (Day 1, Week 0) through Week 24
Secondary	Change From Baseline in Medical Outcomes Study Short Form 36 Item Health Survey Version 2 Acute (SF-36v2) Score	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.	Baseline (Day 1, Week 0) through Week 24
Secondary	Change From Baseline in Patient Global Impression of Severity (PGIS)	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.	Baseline (Day 1, Week 0) through Week 24
Secondary	Patient-reported Status As Assessed by Patient Global Impression of Change (PGIC) Scale Score	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.	At Week 24
Secondary	Hgb Range at Steady State	It will be estimated using a model-based longitudinal analysis of Hgb/hemolysis parameters in relationship to IgG level and dose regimen.	Baseline (Day 1, Week 0) through Week 24
Secondary	Absolute Change from Baseline in Average Daily Dose of Prednisone or Equivalent	Absolute change from baseline in average daily dose of prednisone or equivalent at Week 24 among all participants will be reported.	Baseline (Day 1, Week 0) and at Week 24
Secondary	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	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.	At Week 24