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)
A Phase 3 Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients with Cold Agglutinin Disease (CAD)
Haruki Maeda
CMIC Co., Ltd.
Hamamatsucho Building, 1-1-1, Minato-ku, Shibaura, Tokyo,
+81-3-6779-8000
ClinicalTrialInformation@cmic.co.jp
CMIC Co., Ltd
CMIC Co., Ltd.
Hamamatsucho Building, 1-1-1, Minato-ku, Shibaura, Tokyo,
+81-3-6779-8000
ClinicalTrialInformation@cmic.co.jp
Suspended
Dec. 01, 2022
Mar. 22, 2023
12
Interventional
randomized controlled trial
double blind
placebo control
single assignment
treatment purpose
1. Age 18 years or older.
2. Diagnosis of primary CAD.
3. Hb level <_ 9 g/dL.
4. An absolute neutrophil count >_ 1500 cells/mm3 at screening.
5. Documented results from bone marrow biopsy within 1 year of screening
6. 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.
7. 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.
8. Men must agree to the following for the duration of the study and 8 weeks after their last IMP dose:
a. Avoid fathering a child.
b. Use protocol-defined methods of contraception.
c. Refrain from donating sperm.
9. Willing and able to give written informed consent.
1. Have received other anticomplement 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. Use of prohibited medications.
4. Diagnosis of systemic lupus erythematosus or other autoimmune disease with antinuclear antibodies.
5. History of an aggressive lymphoma or presence of a lymphoma requiring therapy.
6. Have received an organ transplant.
7. Cold agglutinin syndrome secondary to Mycoplasma pneumoniae, Epstein-Barr virus or other specific causative infection.
8. HIV or hepatitis C virus detectable by polymerase chain reaction at screening or documented in the patient's medical record.
9. Chronic inactive hepatitis B virus with viral loads > 1000 IU/mL (> 5000 copies/mL) at screening or documented in the patient's medical record. Eligible patients who are chronic active carriers (<_ 1000 IU/mL) must receive prophylactic antiviral treatment (e.g., entecavir, tenofovir, lamivudine) according to local country guidelines.
10. Presence of an active malignant disease within the last 12 months other than skin basal cell carcinoma or in situ carcinoma of the cervix. A low-grade lymphoproliferative bone marrow disorder not requiring therapy by itself is not defined as a malignant disease in this context.
11. A monospecific direct antiglobulin test result of IgG > 1+.
12. Presence or suspicion of liver dysfunction as indicated by elevated ALT > 2.5 x ULN, or direct bilirubin levels > 2 x ULN.
13. Hypersensitivity to pegcetacoplan or to any of the excipients or placebo compounds.
14. Known or suspected hereditary fructose intolerance.
15. Unresolved infection caused by encapsulated bacteria including N. meningitidis, S. pneumoniae and H. influenzae.
16. Presence or suspicion of severe recurrent or chronic infections that, in the opinion of the investigator, increase the patient's risk by participating in the study.
17. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days prior to screening period.
18. If breastfeeding, is unwilling to discontinue for the duration of study and for at least 8 weeks after the final IMP dose.
19. Inability to cooperate with study procedures.
20. Any disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that would cause reasonable suspicion of a disease or condition that may jeopardize the patient's wellbeing, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient unsuitable for this study.
21. Protected adults (guardianship, trusteeship) who are unable to express their consent and persons under court protection.
Response to treatment at Week 24.
Response is defined as:
- An increase in hemoglobin (Hb) of >_ 1.5 g/dL from Baseline or Hb normalization at Week 16; AND
- Maintenance of this effect from Week 16 to Week 24; AND
- The absence of PRBC transfusions (between Week 5 and Week 24).
Swedish Orphan Biovitrum AB (publ)
University of Tsukuba Hospital Institutional Review Board
