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: 1 February 2022
• Main ID: EUCTR2017-003539-12-AT
• Date of registration: 10/10/2017
• Prospective Registration: Yes
• Primary sponsor: Bioverativ USA 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: 15/11/2017
• 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, France, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Spain, 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:
• Body weight of greater than or equal to (>=) 39 kilogram (kg) at Screening
• Confirmed diagnosis of primary cold agglutinin disease (CAD) based on the following criteria: a) Chronic hemolysis, b) Polyspecific direct for C3d, d) Cold agglutinin titer >= 64 at 4 degree Celsius, and e) Immunoglobulin G (IgG) DAT less than or equal to (<=) 1+, and, f) No overt malignant disease
• Hemoglobin level <= 10.0 gram per deciliter (g/dL)
• Bilirubin level above the normal reference range, including patients with Gilbert's Syndrome
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:
• Cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy
• Clinically relevant infection of any kind within the month preceding enrollment (example, active hepatitis C, pneumonia)
• Clinical diagnosis of systemic lupus erythematosus (SLE); or other autoimmune disorders with anti-nuclear antibodies at Screening. Antinuclear 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
• Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening
• Positive human immunodeficiency virus (HIV) antibody at Screening
• Treatment with rituximab monotherapy within 3 months or rituximab combination therapies (example, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment


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-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

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: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Part A: Percentage of Participants With Response (R). A participant 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 primary cold agglutinin disease (CAD) beyond what is permitted per protocol. Additionally, the participant's hemoglobin (Hgb) level must meet the following criterion: Hgb increase greater than or equal to (>=) 1.5 gram per deciliter (g/dL) from baseline (defined as the last Hgb value before administration of the first dose of study drug.
Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs). An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Secondary Objective: Part A:
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 (acrocyanosis, Raynaud's syndrome, hemoglobinuria, and thromboembolism)
To assess the effect of BIVV009 on quality of life (QOL) in patients with primary CAgD.

Part B:
The secondary objective of Part B is to investigate the durability of response during long-term treatment with BIVV009 in patients with primary CAgD.

Main Objective: The purpose of Part A is to determine whether sutimlimab administration results in a greater than or equal to (>=)1.5 gram per deciliter (g/dL) increase in hemoglobin (Hgb) level and avoidance of transfusion in participants with primary cold agglutinin disease (CAD) without a recent
history of blood transfusion.

The purpose of Part B is to evaluate the long-term safety and tolerability of sutimlimab in participants with primary CAD.

Timepoint(s) of evaluation of this end point: Part A: Up to Week 26
Part B: Approximately 1 year from end of Week 26 of Part A

Secondary Outcome(s)

Secondary end point(s): Part A:
1. Mean Change From Baseline in Hemoglobin (Hgb) Level up to Week 26.
2. Mean Change From Baseline in Bilirubin up to Week 26.
3. Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life). FACITFatigue scale consists of 13 questions 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. The range of possible scores is 0-52, with higher score indicating more fatigue.
4. Mean Change From Baseline in Lactate Dehydrogenase (LDH) up to Week 26.
5. Percentage of Participants With Solicited Symptomatic Anemia at End of Treatment (EOT). Symptomatic anemia is defined as fatigue, weakness, shortness of breath, palpitations, fast heart beat, light headedness, and/or chest pain.
Part B:
6. Mean Change From Week 27 in Hemoglobin (Hgb) Level.
7. Mean Change From Week 27 in Bilirubin (total).
8. Mean Change From Week 27 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life).
FACIT Fatigue scale consists of 13 questions 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. The range of possible scores is 0-52, with higher score indicating more fatigue.
9. Mean Change From Week 27 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. Higher the score better the health.
10. Mean Change From Week 27 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 (Q).
11. Patient's Global Impression of [Fatigue] Severity (PGIS) total score in different timepoints. PGIS is a 5-point response to the severity of the fatigue over the past weeks where 1 indicates No fatigue" to 5 as "very severe". The assessments will be performed every 3 months beginning after Week 27 up to Week 77.
12. Patient's Global Impression of Change (PGIC) total score in different timepoints. PGIC is a 7-point response to the change of overall status of quality of life where 1 indicates "Very much improved" to 7 as "very much worse". The assessments will be performed every 3 months beginning after Week 27 up to Week 77.
13. Mean Change From Week 27 in Lactate Dehydrogenase (LDH) level.
14. Number of transfusions.
15. Mean Change From Week 27 in Haptoglobin.
16. Number of healthcare visits by type. Number of healthcare visits by type such as office visit, hospital ER visit, hospitalization, and ICU stay will be reported for the approximately 1 year duration of Part B.

Timepoint(s) of evaluation of this end point: 1, 2, 3, 4. Baseline Up to Week 26
5. At Part A EOT (Day 182)
6, 7, 8, 9, 10, 11, 12, 13, 14, 15. From Week 27 (Part B baseline ) up to Week 77
16. Approximately 1 year from end of Week 26 of Part A

Secondary ID(s)

NCT03347422

128,190

EFC16216

Source(s) of Monetary Support

Bioverativ USA Inc.

Ethics review

Status: Approved
Approval date: 07/11/2017
Contact: