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

Study Overview
=================
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).

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)

Conditions
-----------------
Cold Agglutinin Disease

Intervention / Treatment
-----------------
* Drug: Pegcetacoplan


Participation Criteria
=================
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 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 ULN, or direct bilirubin levels > 2 x ULN. Inability to cooperate with study procedures.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pegcetacoplan<br>1080 mg, subcutaneus injection, twice weekly | Drug: Pegcetacoplan<br>* Pegcetacoplan taken twice weekly as subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>Sodium acetate, subcutaneus injection, twice weekly | Drug: Pegcetacoplan<br>* Pegcetacoplan taken twice weekly as subcutaneous injection<br>|

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 |