A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)
- Registration Number
- NCT05096403
- Lead Sponsor
- Swedish Orphan Biovitrum
- Brief Summary
The purpose of the study is to determine the efficacy of pegcetacoplan administration compared to placebo in increasing hemoglobin (Hgb) level from baseline and avoiding transfusion in participants with primary cold agglutinin disease (CAD).
- Detailed Description
This is a blind (actual treatment not disclosed to Investigator or participant) study to study pegcetacoplan in people with cold agglutinin disease. The study will consist of a 4-week screening period where selected tests will be conducted to ensure that the patient is eligible to participate in the study, followed by Part A, a 24-week blinded treatment period where the participants will receive either pegcetacoplan or a placebo treatment, looking like pegcetacoplan but with no effect. After this period, the participants will move into Part B, a 24-week period where they will all receive pegcetacoplan. Part C is a 48-week maintenance period with pegcetacoplan for all participants. After the end of treatment participants will undergo a safety follow visit about 8 weeks after last dose.
All eligible study participants will receive pegcetacoplan or placebo treatment, administered via subcutaneous infusion twice a week at home. The subcutaneous infusion requires two small needles to be inserted into the fatty layer of tissue under the skin and the investigational medication will flow into the body. Study participants and/or caregivers will be trained on home administration of pegcetacoplan.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 57
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Age 18 years or older.
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Diagnosis of primary CAD.
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Hb level ≤ 9 g/dL.
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Documented results from bone marrow biopsy within 1 year of screening
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Either have vaccination against Streptococcus pneumoniae, Neisseria meningitidis (Types A, C, W, Y, and B), and Haemophilus influenzae (Type B) within 2 years prior to screening or agree to receive vaccination during screening.
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Women of childbearing potential (WOCBP), defined as any women who have experienced menarche and who are NOT permanently sterile or postmenopausal, must have a negative pregnancy test at screening and agree to use protocol-defined methods of contraception for the duration of the study and 8 weeks after their last IMP dose.
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Men must agree to the following for the duration of the study and 8 weeks after their last IMP dose:
- Avoid fathering a child.
- Use protocol-defined methods of contraception.
- Refrain from donating sperm.
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Willing and able to give written informed consent.
- Have received other anti-complement therapies (approved or investigational) within 5 half-lives of the agent prior to randomization.
- Treatment with rituximab monotherapy within 12 weeks prior to randomization, or rituximab combination therapies (e.g., with bendamustine, fludarabine, other cytotoxic drugs or ibrutinib) within 16 weeks prior to randomization.
- Diagnosis of systemic lupus erythematosus or other autoimmune diseases with antinuclear antibodies.
- History of an aggressive lymphoma or presence of a lymphoma requiring therapy.
- Have received an organ transplant.
- Cold agglutinin syndrome secondary to Mycoplasma pneumoniae, Epstein-Barr virus or other specific causative infection.
- Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase (ALT) > 2.5 x ULN, or direct bilirubin levels > 2 x ULN.
- Inability to cooperate with study procedures.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pegcetacoplan Pegcetacoplan 1080 mg, subcutaneus injection, twice weekly Placebo Pegcetacoplan Sodium acetate, subcutaneus injection, twice weekly
- Primary Outcome Measures
Name Time Method Response (R) Week 24 A participant will be considered to have a response if the Hgb level increases greater than or equal to (\>=) 1.5 gram per deciliter (g/dL) from baseline and this increase is maintained from Week 16 through Week 24 in absence of blood transfusion from Week 5 through Week 24.
- Secondary Outcome Measures
Name Time Method Transfusion avoidance from Week 5 to Week 24 Week 24 Percentage of patients who did not received a blood transfusion between Week 5 and Week 24 will be assessed
Change from Baseline to Week 24 in Hemoglobin (Hgb) level. Week 24 Mean change from Baseline to Week 24 in Hemoglobin (Hgb) level will be assessed
Change From Baseline to Week 24 in Functional Assessment of Cancer Therapy-Anemia/Fatigue (FACT-An) Scale Score (Quality of Life) Week 24 FACT-An consists consists of 33 questions related to general quality of life and to the impact of fatigue and other anemia-related symptoms assessed using a 5 point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question are added to obtain a total score.
Number of PRBC transfusions from Week 5 to Week 24. Week 24 Number of blood transfusions received between Week 5 and Week 24 will be assessed
Change from Baseline to Week 24 in markers of hemolysis Week 24 Mean change from baseline to Week 24 in Lactate dehydrogenase (LDH) level; Haptoglobin level; Indirect bilirubin level; Absolute reticulocyte counts (ARC).
Normalization of markers of hemolysis at Week 24 Week 24 Percentage of patients with LDH level; Indirect bilirubin level and ARC within normal ranges.
Change From Baseline to Week 24 in 12-item short form survey (SF-12) 24 weeks SF-12 health survey is a self-reported questionnaire to measure participant's profile of functional health and well-being. It includes 12 questions.
Change From Baseline to Week 24 in five level EuroQol five dimensions questionnaire (EQ-5D-5L) Week 24 The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. A scale with score 0-100 is used to collect response on current health status.
Trial Locations
- Locations (44)
Ltd M. Zodelava Hematology Centre
🇬🇪Tbilisi, Georgia
Churchill Hospital
🇬🇧Oxford, United Kingdom
CHU de Liège
🇧🇪Liège, Belgium
St. Michael's Hospital
🇨🇦Toronto, Canada
East Carolina University Division of Hematology/ Oncology
🇺🇸Greenville, North Carolina, United States
"FOND IRCCS Cà Granda Ospedale Maggiore Policlinico
🇮🇹Milano, Italy
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Lakes Research
🇺🇸Miami Lakes, Florida, United States
University of Iowa Hospitals & Clinics - The Hemophilia Treatment Center (HTC)
🇺🇸Iowa City, Iowa, United States
Weill Cornell Medicine / NewYork Presbyterian Hospital
🇺🇸New York, New York, United States
Medical University
🇦🇹Vienna, Austria
Algemeen Ziekenhuis Klina
🇧🇪Brasschaat, Belgium
"LTD Medinvest Institute of Hematology and Transfusiology "
🇬🇪Tbilisi, Georgia
UZ Gasthuisberg
🇧🇪Leuven, Belgium
Helsinki University Hospital - Comprehensive Cancer Center
🇫🇮Helsinki, Finland
Universitätsklinikum Essen Klinik f. Hämatologie - Westdeutsches Tumorzentrum
🇩🇪Essen, Germany
Institut f. Transfusionsmedizin - Universität Ulm
🇩🇪Ulm, Germany
Semmelweis Egyetem
🇭🇺Budapest, Hungary
A.O.R.N. S.G. Moscati di Avellino
🇮🇹Avellino, Italy
ASST degli Spedali Civili di Brescia_Presidio Ospedaliero di Brescia_U.O. Ematologia
🇮🇹Brescia, Italy
AOU Maggiore della Carità SCDU Ematologia
🇮🇹Novara, Italy
Azienda Ospedaliera Ospedali Riuniti ""Villa Sofia-Cervello
🇮🇹Palermo, Italy
Grande Ospedale Metropolitano ""Bianchi - Melacrino - Morellii
🇮🇹Reggio Calabria, Italy
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
University of Tsukuba Hospital
🇯🇵Ibaraki, Japan
Ishikawa Prefectural Central Hospital
🇯🇵Kanazawa, Japan
Aichi Medical University Hospital
🇯🇵Nagakute, Japan
Shinshu University Hospital
🇯🇵Nagano, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
Haukeland University Hospital
🇳🇴Bergen, Norway
Sykehuset Østfold Kalnes
🇳🇴Grålum, Norway
St Olavs Hospital, Avdeling for blodsykdommer
🇳🇴Trondheim, Norway
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario de Gran Canaria Dr. Negrin
🇪🇸Las Palmas De Gran Canaria, Spain
Hospital Clínico Universitario de Salamanca
🇪🇸Madrid, Spain
Hospital Universitario Infanta Leonor
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Universitario y Politecnico La Fe
🇪🇸Valencia, Spain
St James' University Hospital
🇬🇧Leeds, United Kingdom
Royal London Hospital
🇬🇧London, United Kingdom
Cancer Clinical Trials Unit, Haematology -University College London -
🇬🇧London, United Kingdom
Russell Centre for Clinical Haematology
🇬🇧Nottingham, United Kingdom