Phase 3 N=24 Randomized Quadruple-blind Treatment

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

Cold Agglutinin Disease

Bottom Line

View on ClinicalTrials.gov: NCT05096403 ↗

Enrolled (actual)

Serious AEs

28.9%

Results posted

Oct 2025

Primary outcome: Primary: Number of Patients Achieving a Response (R) at Week 24 — 8; 2 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Pegcetacoplan (Drug); Placebo matching Pegcetacoplan (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Swedish Orphan Biovitrum
Primary completion: May 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Patients Achieving a Response (R) at Week 24	8; 2	—
SECONDARY Change From Baseline to Week 24 in Hemoglobin (Hgb) Level-Part A in the Absence of Intercurrent Events (ICEs).	2.85; 1.36	—
SECONDARY Number of Patients Achieving Transfusion Avoidance From Week 5 to Week 24-Part A	12; 5	—
SECONDARY Change From Baseline to Week 24 in FACT-An Scale Score (Quality of Life)-Part A in the Absence of Intercurrent Events (ICEs)	20.67; 16.40	—
SECONDARY Number of Packed Red Blood Cell Transfusions Received by Patients From Week 5 to Week 24-Part A	1.5; 1.1	—
SECONDARY Change From Baseline to Week 24 in LDH Levels-Part A in the Absence of Intercurrent Events (ICEs)	-251.73; -82.00	—
SECONDARY Change From Baseline to Week 24 in Haptoglobin Levels-Part A in the Absence of Intercurrent Events (ICEs)	0.31; 0.01	—
SECONDARY Change From Baseline to Week 24 in Indirect Bilirubin-Part A in the Absence of Intercurrent Events (ICE)	-31.55; 8.20	—
SECONDARY Change From Baseline to Week 24 in ARC-Part A in the Absence of Intercurrent Events (ICEs)	-41.17; -37.96	—
SECONDARY Change From Baseline to Week 24 in D-dimer Levels-Part A in the Absence of Intercurrent Events (ICEs	-698.70; -1722.75	—
SECONDARY Normalization of Markers of Hemolysis (LDH) at Week 24-Part A	5; 1	—
SECONDARY Normalization of Markers of Hemolysis (Indirect Bilirubin) at Week 24-Part A	9; 1	—
SECONDARY Normalization of Markers of Hemolysis (ARC) at Week 24-Part A	4; 2	—
SECONDARY Normalization of Markers of Hemolysis (Haptoglobin) at Week 24-Part A	4; 0	—
SECONDARY Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Haptoglobin Levels-Part A	7; 0	—
SECONDARY Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Hemoglobin Levels-Part A	7; 0	—
SECONDARY Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for LDH Levels-Part A	6; 2	—
SECONDARY Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Indirect Bilirubin Levels-Part A	11; 1	—
SECONDARY Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for ARC Levels-Part A	9; 3	—
SECONDARY Number of Packed Red Blood Cell Units Transfused From Week 5 to Week 24-Part A	2.47; 1.88	—
SECONDARY Change From Baseline to Week 24 in FACIT-F Subscale Score-Part A in the Absence of Intercurrent Events (ICEs)	9.73; 8.80	—
SECONDARY Change From Baseline to Week 24 in SF-12-Part A in the Absence of Intercurrent Events (ICEs)	4.95; 4.46; 5.53; 2.50	—
SECONDARY Change From Baseline to Week 24 in EQ-5D-5L Questionnaire -Part A in the Absence of Intercurrent Events (ICEs)	0.50; 0.00; 0.00; 1.00; 0.58; 0.00	—
SECONDARY Change From Baseline to Week 48 in Hemoglobin (Hgb) Level-Part B in the Absence of Intercurrent Events (ICEs).	3.00; 3.35	—
SECONDARY Change From Baseline to Week 48 in LDH Level-Part B in the Absence of Intercurrent Events (ICEs).	-220.25; -259.25	—
SECONDARY Change From Baseline to Week 48 in Haptoglobin Level-Part B in the Absence of Intercurrent Events (ICEs).	0.18; 0.69	—
SECONDARY Change From Baseline to Week 48 in Indirect Bilirubin Level-Part B in the Absence of Intercurrent Events (ICEs).	-40.19; -33.43	—
SECONDARY Change From Baseline to Week 48 in ARC-Part B in the Absence of Intercurrent Events (ICEs)	-39.64; -118.20	—
SECONDARY Change From Baseline to Week 48 in D-dimer Levels-Part B in the Absence of Intercurrent Events (ICEs).	-596.63; -3595.00	—
SECONDARY Change From Baseline to Week 48 in FACT-An Scale Score (Quality of Life)-Part B in the Absence of Intercurrent Events (ICEs)	29.20; 39.50	—
SECONDARY Change From Baseline to Week 48 in FACIT-F Subscale Score-Part B in the Absence of Intercurrent Events (ICEs).	11.82; 21.75	—
SECONDARY Change From Baseline to Week 48 in EQ-5D-5L-Part B in the Absence of Intercurrent Events (ICEs).	0.60; 1.25; 0.10; 1.25; 0.70; 0.75	—
SECONDARY Change From Baseline to Week 48 in SF-12-Part B in the Absence of Intercurrent Events (ICEs).	7.70; 14.49; 3.93; 4.10	—

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).

Eligibility Criteria

Inclusion Criteria

Age 18 years or older.
Diagnosis of primary CAD.
Hb level ≤ 9 g/dL.
Documented results from bone marrow biopsy within 1 year of screening
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.
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 investigational medicinal product (IMP) dose.
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.
Willing and able to give written informed consent.

Exclusion Criteria

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 upper limit of normal (ULN), or direct bilirubin levels > 2 x ULN.
Inability to cooperate with study procedures.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05096403). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.