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

Phase 3

Completed

Conditions: Cold Agglutinin Disease

Interventions: Drug: Pegcetacoplan
Drug: Placebo matching Pegcetacoplan

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: COMPLETED

Sex: All

Target Recruitment: 57

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:
1. Avoid fathering a child.
2. Use protocol-defined methods of contraception.
3. 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pegcetacoplan Double Blind During Part A	Pegcetacoplan	1080 mg, subcutaneous injection, twice weekly
Placebo Matching Pegcetacoplan-Double-blind During Part A	Placebo matching Pegcetacoplan	Sodium acetate, subcutaneous injection, twice weekly
Open-label Pegcetacoplan During Parts B and C	Pegcetacoplan	1080 mg, subcutaneous injection, twice weekly
Open-label Pegcetacoplan (Placebo Matching Pegcetacoplan During Part A) During Parts B&C	Placebo matching Pegcetacoplan	Sodium acetate, subcutaneous injection, twice weekly

Primary Outcome Measures

Name	Time	Method
Number of Patients Achieving a Response (R) at Week 24	Week 24	A participant was considered to have a response if the Hgb level increased greater than or equal to (\>=) 1.5 gram per deciliter (g/dL) from baseline and this increase was maintained from Week 16 through Week 24 in absence of blood transfusion from Week 5 through Week 24.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Week 24 in Hemoglobin (Hgb) Level-Part A in the Absence of Intercurrent Events (ICEs).	Week 24	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange) Mean change from Baseline to Week 24 in Hemoglobin (Hgb) level.
Number of Patients Achieving Transfusion Avoidance From Week 5 to Week 24-Part A	Week 24	Percentage of patients who did not receive a blood transfusion between Week 5 and Week 24 was assessed
Change From Baseline to Week 24 in FACT-An Scale Score (Quality of Life)-Part A in the Absence of Intercurrent Events (ICEs)	Week 24	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). FACT-An is used to measure quality of life (QoL) in patients with anemia. Each item is rated on a 5-point Likert scale:0=Not at all, 1=A little bit ,2=Somewhat, 3=Quite a bit, 4=Very much. Some items are reverse scored. Higher scores in this scale denote a better QoL with less impact of anemia.The total FACT-An scale score ranges from 0 to 160. The total score gives a comprehensive view of a patient's well-being. It combines the FACT-G with an Anemia subscale. FACT-G (27 items):Physical Well-Being (PWB) and Social/Family Well-Being (SWB) 14 items in total, Emotional Well-Being (EWB)-6 items,Functional Well-Being (FWB)-7 items, Anemia Subscale (AnS): 13 items. Total FACT-An score=FACT-G + Anemia Subscale=40 item
Number of Packed Red Blood Cell Transfusions Received by Patients From Week 5 to Week 24-Part A	Week 24	Number of blood transfusions received between Week 5 and Week 24 were assessed.
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for ARC Levels-Part A	Week 24	Percentage of patients with ARC level normalization during the initial 24 weeks of the study
Change From Baseline to Week 24 in LDH Levels-Part A in the Absence of Intercurrent Events (ICEs)	Week 24	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange) Mean change from baseline to Week 24 in Lactate dehydrogenase (LDH) levels
Change From Baseline to Week 24 in Haptoglobin Levels-Part A in the Absence of Intercurrent Events (ICEs)	Week 24	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from baseline to Week 24 in Haptoglobin level
Change From Baseline to Week 24 in Indirect Bilirubin-Part A in the Absence of Intercurrent Events (ICE)	Week 24	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from baseline to Week 24 in Indirect bilirubin level
Change From Baseline to Week 24 in ARC-Part A in the Absence of Intercurrent Events (ICEs)	Week 24	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from baseline to Week 24 in Absolute reticulocyte counts (ARC).
Change From Baseline to Week 24 in D-dimer Levels-Part A in the Absence of Intercurrent Events (ICEs	Week 24	* Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange) change from baseline to Week 24 in D-dimer levels.
Normalization of Markers of Hemolysis (LDH) at Week 24-Part A	Week 24	Percentage of patients with LDH level within normal ranges and with an abnormal value at baseline.
Normalization of Markers of Hemolysis (Indirect Bilirubin) at Week 24-Part A	Week 24	Percentage of patients with Indirect Bilirubin level within normal ranges and with an abnormal value at baseline.
Normalization of Markers of Hemolysis (ARC) at Week 24-Part A	Week 24	Percentage of patients with ARC level within normal ranges and with an abnormal value at baseline.
Normalization of Markers of Hemolysis (Haptoglobin) at Week 24-Part A	Week 24	Percentage of patients with haptoglobin level within normal ranges and with an abnormal value at baseline.
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Haptoglobin Levels-Part A	Week 24	Percentage of patients with haptoglobin level normalization during the initial 24 weeks of the study
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Hemoglobin Levels-Part A	Week 24	Percentage of patients with Hemoglobin level normalization during the initial 24 weeks of the study
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for LDH Levels-Part A	Week 24	Percentage of patients with LDH level normalization during the initial 24 weeks of the study
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Indirect Bilirubin Levels-Part A	Week 24	Percentage of patients with Indirect Bilirubin level normalization during the initial 24 weeks of the study
Number of Packed Red Blood Cell Units Transfused From Week 5 to Week 24-Part A	Week 5 to Week 24	Number of PRBC units transfused from Week 5 and Week 24 was assessed
Change From Baseline to Week 24 in FACIT-F Subscale Score-Part A in the Absence of Intercurrent Events (ICEs)	Week 24	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). The FACIT-F subscale is used to measure fatigue and its impact upon daily activities and function in patients with chronic illnesses and contains 20 items related to the impact of fatigue. Each item is scored on a 0-4 scale, with some items reverse-scored. Total scores range from 0 to 52, where higher scores indicate less fatigue and better outcomes, and lower scores reflect greater fatigue. It can be used alone or with other FACIT subscales as part of broader quality of life assessments.
Change From Baseline to Week 24 in SF-12-Part A in the Absence of Intercurrent Events (ICEs)	Week 24	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange. SF-12 is a 12-item health survey assessing physical and mental health. Higher scores mean better health with scores above 50 indicating better than average health. It produces two summary scores: the Physical Component Summary (PCS) and Mental Component Summary (MCS), both norm-based (mean=50, SD=10), with ranges of \~5-80 (PCS) and \~-3.3-80 (MCS). Higher scores=better health. It also covers 8 subscales-Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH), each scored between 0-100, where higher=better functioning. Scores are computed using weighted formulas from item responses (not simple averages).
Change From Baseline to Week 24 in EQ-5D-5L Questionnaire -Part A in the Absence of Intercurrent Events (ICEs)	Week 24	The EQ-5D-5L measures total health across 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression-each scored from 1 (no problems) to 5 (extreme problems). Scores form a 5-digit health profile (e.g., 12345). Each individual score plus a VAS for perceived health status today are separately reported. Higher scores reflect better total health. The EQ VAS is a patient-rated score from 0 (worst) to 100 (best health). The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange).
Change From Baseline to Week 48 in Hemoglobin (Hgb) Level-Part B in the Absence of Intercurrent Events (ICEs).	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from Baseline to Week 48 in Hemoglobin (Hgb) level.
Change From Baseline to Week 48 in LDH Level-Part B in the Absence of Intercurrent Events (ICEs).	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from Baseline to Week 48 in LDH level.
Change From Baseline to Week 48 in Haptoglobin Level-Part B in the Absence of Intercurrent Events (ICEs).	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from Baseline to Week 48 in Haptoglobin level
Change From Baseline to Week 48 in Indirect Bilirubin Level-Part B in the Absence of Intercurrent Events (ICEs).	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from Baseline to Week 48 in Indirect Bilirubin level.
Change From Baseline to Week 48 in ARC-Part B in the Absence of Intercurrent Events (ICEs)	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from baseline to Week 48 in Absolute reticulocyte counts (ARC).
Change From Baseline to Week 48 in D-dimer Levels-Part B in the Absence of Intercurrent Events (ICEs).	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). Mean change from baseline to Week 48 in D-dimer levels.
Change From Baseline to Week 48 in FACT-An Scale Score (Quality of Life)-Part B in the Absence of Intercurrent Events (ICEs)	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug and plasma exchange. The FACT-An is used to measure quality of life (QoL) in patients with anemia. Each item is rated on a 5-point Likert scale:0=Not at all, 1=A little bit ,2=Somewhat, 3=Quite a bit, 4=Very much.Some items are reverse scored. Higher scores in this scale denote a better QoL with less impact of anemia. The total FACT-An scale score ranges from 0 to 160. The total score gives a comprehensive view of a patient's well-being. It combines the FACT-G with an Anemia subscale.FACT-G (27 items):Physical Well-Being (PWB) and Social/Family Well-Being (SWB) 14 items in total, Emotional Well-Being (EWB)-6 items, Functional Well-Being (FWB)-7 items, Anemia Subscale (AnS): 13 items. Total FACT-An score=FACT-G + Anemia Subscale=40 items
Change From Baseline to Week 48 in FACIT-F Subscale Score-Part B in the Absence of Intercurrent Events (ICEs).	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). The FACIT-F subscale is used to measure fatigue and its impact upon daily activities and function in patients with chronic illnesses and contains 20 items related to the impact of fatigue. Each item is scored on a 0-4 scale, with some items reverse-scored. Total scores range from 0 to 52, where higher scores indicate less fatigue and better outcomes, and lower scores reflect greater fatigue. It can be used alone or with other FACIT subscales as part of broader quality of life assessments.
Change From Baseline to Week 48 in EQ-5D-5L-Part B in the Absence of Intercurrent Events (ICEs).	Week 48	The EQ-5D-5L measures total health across 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression-each scored from 1 (no problems) to 5 (extreme problems). Scores form a 5-digit health profile (e.g., 12345). Each individual score plus a VAS for perceived health status today are separately reported. Higher scores reflect better total health. The EQ VAS is a patient-rated score from 0 (worst) to 100 (best health). The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange).
Change From Baseline to Week 48 in SF-12-Part B in the Absence of Intercurrent Events (ICEs).	Week 48	The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange SF-12 is a 12-item health survey assessing physical and mental health. Higher scores mean better health with scores above 50 indicating better than average health. It produces two summary scores: the Physical Component Summary (PCS) and Mental Component Summary (MCS), both norm-based (mean = 50, SD =10), with ranges of \~5-80 (PCS) and \~-3.3-80 (MCS). Higher scores = better health. It also covers 8 subscales-Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH), each scored between 0-100, where higher=better functioning. Scores are computed using weighted formulas from item responses (not simple averages).

Trial Locations

Locations (44): 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
East Carolina University Division of Hematology/ Oncology
🇺🇸
Greenville, North Carolina, United States
Medical University
🇦🇹
Vienna, Austria
Algemeen Ziekenhuis Klina
🇧🇪
Brasschaat, Belgium
UZ Gasthuisberg
🇧🇪
Leuven, Belgium
CHU de Liège
🇧🇪
Liège, Belgium
St. Michael's Hospital
🇨🇦
Toronto, Canada
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The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States