A PHASE 3, PIVOTAL, OPEN-LABEL, MULTICENTER STUDY TO ASSESS THEEFFICACY AND SAFETY OF BIVV009 IN PATIENTS WITH PRIMARY COLD AGGLUTININ DISEASE WHO HAVE A RECENT HISTORY OF BLOOD TRANSFUSION - Cardinal Study

Phase 1

• Conditions: Primary Cold Agglutinin Disease; MedDRA version: 20.0Level: PTClassification code 10073785Term: Autoimmune haemolytic anaemiaSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2017-003538-10-AT
• Lead Sponsor: Bioverativ USA Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-10-10
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1.Adult males and females = 18 years of age at Screening
2.Body weight of = 39 kg at screening
3.Confirmed diagnosis of primary CAgD based on the following criteria:
a.Chronic hemolysis,
b.Polyspecific direct antiglobulin test (DAT) positive,
c.Monospecific DAT strongly positive for C3d,
d.Cold agglutinin titer = 64 at 4 degrees Celsius,
e.IgG DAT = 1+, and
f.No overt malignant disease
4.History of at least one documented blood transfusion within 6 months of enrollment
5.Hemoglobin level = 10.0 g/dL
6.Bilirubin level above the normal reference range, including patients with Gilbert’s Syndrome
7.Ferritin levels above the lower limit of normal. Concurrent treatment with iron supplementation is permitted if the patient has been on a stable dose during the previous 4 weeks.
8.Presence of one or more of the following CAgD-related signs or symptoms within 3 months of Screening:
a.Symptomatic anemia defined as:
i.Fatigue,
ii.Weakness,
iii.Shortness of breath,
iv.Palpitations, fast heart beat
v.Light headedness and/or
vi.Chest pain
b.Acrocyanosis
c.Raynaud’s syndrome
d.Hemoglobinuria
e.Disabling circulatory symptoms, and/or
f.Major adverse vascular event (including thrombosis)
9.Bone marrow biopsy within 6 months of Screening with no overt evidence of lymphoproliferative disease or other hematological malignancy. An additional bone marrow biopsy will be required if the prior bone marrow is deemed unsuitable for analysis by the Sponsor.
10.Documented Vaccinations against encapsulated bacterial pathogens (Neisseria meningitis, including serogroup B meningococcus where available, Haemophilus influenzae, and Streptococcus pneumoniae) within 5 years of enrollment or as specified in Section 6.1.1.1.
11. Adequate IV access
12. If female, must be post-menopausal, surgically sterile, or be established on (= 3 months prior to Screening) and agree to continue to use the same highly effective methods of birth control throughout the study and for 9 weeks following administration of the last dose of study drug
13. Males must be surgically sterile for at least 90 days or when sexually active with female partners of child-bearing potential will agree to use highly effective contraception from Day 0 until 9 weeks days following administration of the last dose of study drug.
14. Able to comprehend and give informed consent
15. Able to comply with the requirements of the study and to complete the full sequence of protocol-related procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1.Cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy
2.Clinically relevant infection of any kind within the month preceding enrollment (eg, active hepatitis C, pneumonia)
3.Clinical diagnosis of systemic lupus erythematosus (SLE) or other autoimmune disorders with anti-nuclear antibodies at Screening. Anti-nuclear antibodies of long-standing duration without associated clinical symptoms will be adjudicated on a case-by-case basis during the Confirmatory Review of Patient Eligibility (Section 6.1.1.3).
4.Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening
5.Positive human immunodeficiency virus (HIV) antibody at Screening
6.Treatment with rituximab monotherapy within 3 months or rituximab combination therapies (eg, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment
7.Concurrent treatment with corticosteroids other than a stable daily dose equivalent to = 10 mg/day prednisone for previous 3 months
8.Erythropoietin deficiency. Concurrent treatment with erythropoietin is permitted if the patient has been on a stable dose for the previous 3 months.
9.Concurrent usage of iron supplementation unless the patient has been on a stable dose for at least 4 weeks.
10.Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the patient or compromise the quality of the data derived from his/her participation in this study (as determined by the Investigator [or designee]) at Screening
11.Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days or 5 half lives, whichever is greater, prior to treatment start
12.Females who are pregnant, lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice.
13. History of hypersensitivity to BIVV009 or any of its components.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified