A study to determine the safety and effectiveness of study drug BIVV009 in patients with Primary Agglutinin Disease without recent history of blood transfusions

• Register: EUCTR
• Last refreshed on: 14 October 2024
• Main ID: EUCTR2017-003539-12-IT
• Date of registration: 15/01/2021
• Prospective Registration: No
• Primary sponsor: BIOVERATIV THERAPEUTICS INC
• Public title: A study to determine the safety and effectiveness of study drug BIVV009 in patients with Primary Agglutinin Disease without recent history of blood transfusions
• Scientific title: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF BIVV009 IN PATIENTS WITH PRIMARY COLD AGGLUTININ DISEASE WITHOUT A RECENT HISTORY OF BLOOD TRANSFUSION - Cadenza
• Date of first enrolment: 19/03/2018
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003539-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Trial Dept
• Affiliation: Pharm-Olam LLC

• Name: Clinical Trial Dept
• Affiliation: Pharm-Olam LLC

Key inclusion & exclusion criteria

Inclusion criteria:
All patients must meet all the following inclusion criteria to be enrolled:
1. Adult male and female patients = 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¿C
e. IgG DAT = 1+, and
f. No overt malignant disease
4. Hemoglobin level = 10.0 g/dL
5. Bilirubin level above the normal reference range, including patients with Gilbert’s Syndrome
6. 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.
7. 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)
8. 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.
9. 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
10. Patients must be willing to receive transfusions if they meet the eligibility criteria during the study treatment period. Patients who do not have a recent history of transfusion due to patient refusal or patient decision should not be enrolled if they do not agree to receive blood transfusions as needed.
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 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 4
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion criteria:
Patients who meet any of the following criteria will be excluded from the study:
1. Cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy
2. History of blood transfusion within 6 months of screening, or history of more than one blood transfusion within 12 months of screening
3. Clinically relevant infection of any kind within the month preceding enrollment (eg, active hepatitis C, pneumonia)
4. 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).
5. Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening
6. Positive human immunodeficiency virus (HIV) antibody at Screening
7. 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
8. Concurrent treatment with corticosteroids other than a stable daily dose equivalent to
= 10 mg/day prednisone for previous 3 months
9. Erythropoietin deficiency. Concurrent treatment with erythropoietin is permitted if the patient has been on a stable dose for the previous 3 months.
10. Concurrent usage of iron supplementation unless the patient has been on a stable dose for at least 4 weeks.
11. 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
12. 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
13. Females who are pregnant, lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice
14. History of hypersensitivity to BIVV009 or any of its components.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary Cold Agglutinin Disease
MedDRA version: 20.0 Level: PT Classification code 10073785 Term: Autoimmune haemolytic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: BIVV009
Product Code: BIVV009
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BIVV009
Current Sponsor code: BIVV009
Other descriptive name: TNT009
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 18-
INN or Proposed INN: BIVV009
Current Sponsor code: BIVV009
Other descriptive name: TNT009
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the responder rate:
A patient will be considered a responder if he or she did not receive a
blood transfusion from Week 5 through Week 26 (EOT) and did not
receive treatment for CAgD beyond what is permitted per protocol.
Additionally, the patient's Hgb level must meet the following criterion:
•Hgb increase = 1.5 g/dL from baseline (defined as the last Hgb value
before administration of the first dose of study drug) at treatment
assessment endpoint (defined as mean value from Weeks 23, 25, and
26)

Main Objective: The primary objective of Part A is to determine whether BIVV009 administration results in a = 1.5 g/dL increase in hemoglobin (Hgb) level
and avoidance of transfusion in patients with primary CAgD without a
recent history of blood transfusion.
The primary objective of Part B is to evaluate the long-term safety and
tolerability of BIVV009 in patients with primary CAgD.

Secondary Objective: The secondary efficacy objectives of Part A are:
To assess the effect of BIVV009 on clinical events and laboratory
parameters related to hemolysis and anemia in patients with primary
CAgD
To assess the effect of BIVV009 on specific complications of CAgD
To assess the effect of BIVV009 on quality of life (QOL) in patients with
primary CAgD.
The secondary objective of Part B is to investigate the durability of
response during long-term treatment with BIVV009 in patients with
primary CAgD.

Timepoint(s) of evaluation of this end point: Week 26

Secondary Outcome(s)

Secondary end point(s): Secondary Efficacy Endpoints (Part A) Mean change from baseline in Hgb at treatment assessment endpoint (mean of values at Week 23, 25, and 26) Mean change from baseline in bilirubin (excluding patients with Gilbert's Syndrome) at treatment assessment endpoint Mean change from baseline in QOL, as assessed by the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale scores at the treatment assessment endpoint Mean change from baseline in lactate dehydrogenase (LDH) at the treatment assessment endpoint Incidence of solicited symptomatic anemia at EOT Efficacy Endpoints (Part B) The following parameters of disease activity will be assessed: ¿Hemoglobin ¿Bilirubin (total) ¿QOL assessments (FACIT-fatigue, EQ-5D-5L, SF-12, and PGIC Scale) ¿LDH ¿Transfusion requirements ¿Haptoglobin
Total healthcare resource utilization at EOT

Timepoint(s) of evaluation of this end point: Week 23, 25 and 26

Secondary ID(s)

2017-003539-12-AT

BIVV009-04

BIVV009-04

Source(s) of Monetary Support

Bioverativ USA Inc.

Ethics review

Status: Approved
Approval date: 09/01/2018
Contact:

Results

• Results available: Yes
• Date Posted: 16/12/2022
• Date Completed: 03/12/2021
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-003539-12/results