A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)

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)

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).

Study Overview

• Status: Suspended
• Conditions: Cold Agglutinin Disease
• Intervention / Treatment: Drug: Pegcetacoplan

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.

• Study Type: Interventional
• Enrollment (Estimated): 57
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bodil Svanberg; Phone Number: +46733319155; Email: Bodil.Svanberg@sobi.com
• Study Contact Backup: Name: Luis López Lazaro, MD; Phone Number: +41 79 834 17 78; Email: Luis.LopezLazaro@sobi.com

Study Locations

• Austria
  • Vienna, Austria
    • Medical University
• Belgium
  • Brasschaat, Belgium, 2930
    • Algemeen Ziekenhuis Klina
  • Leuven, Belgium, 3000
    • Uz Gasthuisberg
  • Liège, Belgium, 4000
    • CHU de Liege
• Canada
  • Toronto, Canada
    • St. Michael's Hospital
• Finland
  • Helsinki, Finland
    • Helsinki University Hospital - Comprehensive Cancer Center
• Georgia
  • Tbilisi, Georgia
    • "LTD Medinvest Institute of Hematology and Transfusiology "
  • Tbilisi, Georgia
    • Ltd M. Zodelava Hematology Centre
• Germany
  • Essen, Germany, 45147
    • Universitätsklinikum Essen Klinik f. Hämatologie - Westdeutsches Tumorzentrum
  • Ulm, Germany
    • Institut f. Transfusionsmedizin - Universität Ulm
• Hungary
  • Budapest, Hungary
    • Semmelweis Egyetem
• Italy
  • Avellino, Italy, 83100
    • A.O.R.N. S.G. Moscati di Avellino
  • Brescia, Italy, 25123
    • ASST degli Spedali Civili di Brescia_Presidio Ospedaliero di Brescia_U.O. Ematologia
  • Milano, Italy
    • "FOND IRCCS Cà Granda Ospedale Maggiore Policlinico
  • Novara, Italy
    • AOU Maggiore della Carità SCDU Ematologia
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti ""Villa Sofia-Cervello
  • Reggio Calabria, Italy, 89133
    • Grande Ospedale Metropolitano ""Bianchi - Melacrino - Morellii
• Japan
  • Fukushima, Japan
    • Fukushima Medical University Hospital
  • Ibaraki, Japan
    • University of Tsukuba Hospital
  • Kanazawa, Japan, 9208530
    • Ishikawa Prefectural Central Hospital
  • Nagakute, Japan, 480-1195
    • Aichi Medical University Hospital
  • Nagano, Japan
    • Shinshu University Hospital
  • Osaka, Japan, 5650871
    • Osaka University Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC
• Norway
  • Bergen, Norway
    • Haukeland University Hospital
  • Grålum, Norway
    • Sykehuset Østfold Kalnes
  • Trondheim, Norway
    • St Olavs Hospital, Avdeling for blodsykdommer
• Spain
  • Barcelona, Spain
    • Hospital Clínic de Barcelona
  • Las Palmas De Gran Canaria, Spain
    • Hospital Universitario de Gran Canaria Dr. Negrin
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain
    • Hospital Universitario Infanta Leonor
  • Madrid, Spain
    • Hospital Clínico Universitario de Salamanca
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain
    • Hospital Universitario y Politécnico La Fe
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James' University Hospital
  • London, United Kingdom, E1 2ES
    • Royal London Hospital
  • London, United Kingdom
    • Cancer Clinical Trials Unit, Haematology -University College London -
  • Nottingham, United Kingdom, NG5 1PB
    • Russell Centre for Clinical Haematology
  • Oxford, United Kingdom
    • Churchill Hospital
• United States
  • California
    • Whittier, California, United States, 90603
      • The Oncology Institute of Hope and Innovation
  • Florida
    • Miami Lakes, Florida, United States, 33014
      • Lakes Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics - The Hemophilia Treatment Center (HTC)
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medicine / NewYork Presbyterian Hospital
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • East Carolina University Division of Hematology/ Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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
Active Comparator: Pegcetacoplan; 1080 mg, subcutaneus injection, twice weekly	Drug: Pegcetacoplan; Pegcetacoplan taken twice weekly as subcutaneous injection; Other Names: Aspaveli
Placebo Comparator: Placebo; Sodium acetate, subcutaneus injection, twice weekly	Drug: Pegcetacoplan; Pegcetacoplan taken twice weekly as subcutaneous injection; Other Names: Aspaveli

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response (R)	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.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Week 24 in Hemoglobin (Hgb) level.	Mean change from Baseline to Week 24 in Hemoglobin (Hgb) level will be assessed	Week 24
Transfusion avoidance from Week 5 to Week 24	Percentage of patients who did not received a blood transfusion between Week 5 and Week 24 will be assessed	Week 24
Change From Baseline to Week 24 in Functional Assessment of Cancer Therapy-Anemia/Fatigue (FACT-An) Scale Score (Quality of Life)	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.	Week 24
Number of PRBC transfusions from Week 5 to Week 24.	Number of blood transfusions received between Week 5 and Week 24 will be assessed	Week 24
Change from Baseline to Week 24 in markers of hemolysis	Mean change from baseline to Week 24 in Lactate dehydrogenase (LDH) level; Haptoglobin level; Indirect bilirubin level; Absolute reticulocyte counts (ARC).	Week 24
Normalization of markers of hemolysis at Week 24	Percentage of patients with LDH level; Indirect bilirubin level and ARC within normal ranges.	Week 24
Change From Baseline to Week 24 in 12-item short form survey (SF-12)	SF-12 health survey is a self-reported questionnaire to measure participant's profile of functional health and well-being. It includes 12 questions.	24 weeks
Change From Baseline to Week 24 in five level EuroQol five dimensions questionnaire (EQ-5D-5L)	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.	Week 24

Collaborators and Investigators

• Sponsor: Swedish Orphan Biovitrum
• Investigators: Study Director: Luis López Lazaro, Swedish Orphan Biovitrum AB

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: October 15, 2021
• First Submitted That Met QC Criteria: October 15, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: Sobi.PEGCET-101

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