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).

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.

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