Clinical trial NCT05096403: A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cold Agglutinin Disease
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2021-10-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 years or older.
2. Diagnosis of primary CAD.
3. Hb level ≤ 9 g/dL.
4. Documented results from bone marrow biopsy within 1 year of screening
5. 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.
6. 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.
7. Men must agree to the following for the duration of the study and 8 weeks after their last IMP dose:

   1. Avoid fathering a child.
   2. Use protocol-defined methods of contraception.
   3. Refrain from donating sperm.
8. Willing and able to give written informed consent.

Exclusion Criteria:

1. Have received other anti-complement therapies (approved or investigational) within 5 half-lives of the agent prior to randomization.
2. 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.
3. Diagnosis of systemic lupus erythematosus or other autoimmune diseases with antinuclear antibodies.
4. History of an aggressive lymphoma or presence of a lymphoma requiring therapy.
5. Have received an organ transplant.
6. Cold agglutinin syndrome secondary to Mycoplasma pneumoniae, Epstein-Barr virus or other specific causative infection.
7. Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase (ALT) \> 2.5 x ULN, or direct bilirubin levels \> 2 x ULN.
8. Inability to cooperate with study procedures.

Primary outcomes:
measure: Response (R)
timeFrame: Week 24
Secondary outcomes:
measure: Change from Baseline to Week 24 in Hemoglobin (Hgb) level.
timeFrame: Week 24
measure: Transfusion avoidance from Week 5 to Week 24
timeFrame: Week 24
measure: Change From Baseline to Week 24 in Functional Assessment of Cancer Therapy-Anemia/Fatigue (FACT-An) Scale Score (Quality of Life)
timeFrame: Week 24
measure: Number of PRBC transfusions from Week 5 to Week 24.
timeFrame: Week 24
measure: Change from Baseline to Week 24 in markers of hemolysis
timeFrame: Week 24
measure: Normalization of markers of hemolysis at Week 24
timeFrame: Week 24
measure: Change From Baseline to Week 24 in 12-item short form survey (SF-12)
timeFrame: 24 weeks
measure: Change From Baseline to Week 24 in five level EuroQol five dimensions questionnaire (EQ-5D-5L)
timeFrame: Week 24
Other outcomes:
Locations:
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Miami Lakes
country: United States
facility: Lakes Research
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics - The Hemophilia Treatment Center (HTC)
state: Iowa
city: New York
country: United States
facility: Weill Cornell Medicine / NewYork Presbyterian Hospital
state: New York
city: Greenville
country: United States
facility: East Carolina University Division of Hematology/ Oncology
state: North Carolina
city: Vienna
country: Austria
facility: Medical University
city: Brasschaat
country: Belgium
facility: Algemeen Ziekenhuis Klina
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Liège
country: Belgium
facility: CHU de Liège
city: Toronto
country: Canada
facility: St. Michael's Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital - Comprehensive Cancer Center
city: Tbilisi
country: Georgia
facility: "LTD Medinvest Institute of Hematology and Transfusiology "
city: Tbilisi
country: Georgia
facility: Ltd M. Zodelava Hematology Centre
city: Essen
country: Germany
facility: Universitätsklinikum Essen Klinik f. Hämatologie - Westdeutsches Tumorzentrum
city: Ulm
country: Germany
facility: Institut f. Transfusionsmedizin - Universität Ulm
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Avellino
country: Italy
facility: A.O.R.N. S.G. Moscati di Avellino
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia_Presidio Ospedaliero di Brescia_U.O. Ematologia
city: Milano
country: Italy
facility: &#34;FOND IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Novara
country: Italy
facility: AOU Maggiore della Carità SCDU Ematologia
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti ""Villa Sofia-Cervello
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano ""Bianchi - Melacrino - Morellii
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Ibaraki
country: Japan
facility: University of Tsukuba Hospital
city: Kanazawa
country: Japan
facility: Ishikawa Prefectural Central Hospital
city: Nagakute
country: Japan
facility: Aichi Medical University Hospital
city: Nagano
country: Japan
facility: Shinshu University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Grålum
country: Norway
facility: Sykehuset Østfold Kalnes
city: Trondheim
country: Norway
facility: St Olavs Hospital, Avdeling for blodsykdommer
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrin
city: Madrid
country: Spain
facility: Hospital Clínico Universitario de Salamanca
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Leeds
country: United Kingdom
facility: St James' University Hospital
city: London
country: United Kingdom
facility: Royal London Hospital
city: London
country: United Kingdom
facility: Cancer Clinical Trials Unit, Haematology -University College London -
city: Nottingham
country: United Kingdom
facility: Russell Centre for Clinical Haematology
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Swedish Orphan Biovitrum AB
name: Study physician
role: STUDY_DIRECTOR
References: