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

• ClinicalTrials.gov Identifier: NCT05096403
• Recruitment Status: Recruiting
• First Posted: October 27, 2021
• Last Update Posted: March 22, 2022
• Sponsor: Swedish Orphan Biovitrum
• Information provided by (Responsible Party): Swedish Orphan Biovitrum

Tracking Information

• First Submitted Date: October 15, 2021
• First Posted Date: October 27, 2021
• Last Update Posted Date: March 22, 2022
• Estimated Study Start Date: March 2022
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 15, 2021)

Response (R) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 15, 2021)

• Change from Baseline to Week 24 in Hemoglobin (Hgb) level. [ Time Frame: Week 24 ]
  Mean change from Baseline to Week 24 in Hemoglobin (Hgb) level will be assessed
• Transfusion avoidance from Week 5 to Week 24 [ Time Frame: 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 Functional Assessment of Cancer Therapy-Anemia/Fatigue (FACT-An) Scale Score (Quality of Life) [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cold Agglutinin Disease

Intervention

Drug: Pegcetacoplan

Pegcetacoplan taken twice weekly as subcutaneous injection

Study Arms

• Active Comparator: Pegcetacoplan
  1080 mg, subcutaneus injection, twice weekly
  Intervention: Drug: Pegcetacoplan
• Placebo Comparator: Placebo
  Sodium acetate, subcutaneus injection, twice weekly
  Intervention: Drug: Pegcetacoplan

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 15, 2021): 57
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Silvia Mappa, MD; +41 61 508 72 13; Silvia.Mappa@sobi.com

Contact: Bodil Svanberg; +46733319155; Bodil.Svanberg@sobi.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05096403
• Other Study ID Numbers: Sobi.PEGCET-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Swedish Orphan Biovitrum
• Original Responsible Party: Same as current
• Current Study Sponsor: Swedish Orphan Biovitrum
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Bernd Jilma, MD; Medical University of Vienna

• PRS Account: Swedish Orphan Biovitrum
• Verification Date: March 2022