Back to resultsA Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple- Dose BIVV009 in Participants With Chronic Immune Thrombocytopenia (ITP)
Primary Purpose
Purpura, Thrombocytopenic, Idiopathic
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BIVV009 6.5 grams
BIVV009 7.5 grams
Sponsored by
About this trial
This is an interventional treatment trial for Purpura, Thrombocytopenic, Idiopathic focused on measuring Autoimmune Diseases, Hematologic Diseases, Immune System Diseases, Blood Platelet Disorders
Eligibility Criteria
Inclusion Criteria
Part A:
- Chronic immune thrombocytopenia (ITP) (ITP lasting for greater than or equal to ([>=] 12 months) as defined in the protocol
- Normal prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT)
- No history of a coagulation disorder
- Hemoglobin level greater than (>) 10 gram per deciliter (g/dL) (following blood transfusion is acceptable) and normal white blood cell (WBC) and neutrophil counts (elevated WBC/absolute neutrophil count [ANC] attributed to steroid treatment is acceptable)
- Eastern Cooperative Oncology Group (ECOG) performance status grade less than or equal to (<=) 2
- Documented vaccinations against encapsulated bacterial pathogens (Neisseria meningitis, including serogroup B meningococcus [where available], Haemophilus influenzae, and Streptococcus pneumoniae) within 5 years of enrollment
- Adequate intravenous (IV) access
Part B:
- Able to comprehend and to give informed consent for Part B
- History of ITP and previously treated with at least 1 dose of BIVV009 in Part A
- Evidence of treatment efficacy to BIVV009 as defined by a platelet count > 30*10^9/L on at least 1 occasion OR a doubling of the platelet count from baseline
- Participants who have completed the 21-week Part A treatment period but have not reached the Part A End of Study (EOS) visit must have evidence of ongoing or recurrent thrombocytopenia during the Part A safety follow-up/washout period as demonstrated by a platelet count less than (<) 50*10^9/L or a >= 50 percent (%) decrease in platelet count over < 1 week
Exclusion Criteria:
Part A:
- Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his/her participation in this study
- Clinically relevant infection of any kind within the preceding month of enrollment
- History of venous or arterial thrombosis within the preceding year of enrollment
- Use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulants within 1 week of enrollment
- Clinical diagnosis of systemic lupus erythematosus (SLE) or other active autoimmune disorders associated with anti-nuclear antibodies (ANAs) including those that are medically controlled, at Screening (other than ITP)
- Secondary immune thrombocytopenia from any cause including lymphoma, chronic lymphocytic leukemia, and drug-induced thrombocytopenia
- Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening
- Positive human immunodeficiency virus (HIV) test result prior to or at Screening
Part B:
- Presence of unacceptable side effects or toxicity associated with BIVV009 (including prior hypersensitivity reactions to BIVV009) such that there is an unfavorable risk-benefit assessment for continued treatment with BIVV009 in the opinion of the Investigator and/or Sponsor
- For participants who have completed the 9-week safety follow-up/washout period and final study visit before entry into Part B, a positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening. Patients who have undergone hepatitis C antiviral therapy may be allowed if they are documented to be negative for hepatitis C virus ribonucleic acid (RNA) on at least 2 occasions separated by at least 3 months (including 1 RNA test at least 6 months after completion of antiviral therapy) and are also negative for hepatitis C virus RNA at Screening
- Use of prescribed or over-the-counter medications, supplements, vitamins, and/or herbal remedies within 2 weeks before the first dose of BIVV009 in Part B, which in the judgment of the Investigator may adversely affect the participants welfare or the integrity of the study results (excluding hormonal contraception in female participants)
- If previously treated with rituximab, the last dose of rituximab was administered < 12 weeks before the first dose of BIVV009 in Part B
- Clinical diagnosis of systemic lupus erythematosus (SLE) or other active autoimmune disorders associated with anti-nuclear antibodies (ANA), including those that are medically controlled, at Screening (other than ITP). Positive ANAs at screening that are not associated with an autoimmune disorder (other than ITP) may be allowed if present for >= 28 days without associated clinically relevant symptoms
Sites / Locations
- Georgetown Lombardi Comprehensive Cancer Center
- Massachusetts General Hospital - Cancer Center
- University of Pittsburgh Medical Center (UPMC) Hilman Cancer Center
- Essen University Hospital Department of Hematology
- University College Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BIVV009
Arm Description
Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009 intravenous (IV) infusion and participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009 every 2 weeks for approximately 21 weeks in Part A (based on time to complete 11 doses of study drug). There will be a 9-week safety follow-up/washout period after administration of the last dose of study drug in Part A. Participants who have been shown to benefit from BIVV009 treatment during Part A, will receive BIVV009 (based on weight) biweekly for up to 52 weeks of BIVV009 after Last Patient In (LPI) in part B.
Outcomes
Primary Outcome Measures
Incidence of Treatment-Emergent Adverse Events
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A serious adverse event (SAE) is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Number of Participants With Premature Study Terminations
Number of participants with premature study terminations will be assessed.
Number of Participants With Clinical Laboratory Abnormalities
Clinical laboratory abnormalities including one or more specific target-organs for toxicity of BIVV009, abnormalities in D-dimer, thrombin-anti-thrombin assay, and Systemic Lupus Erythematosus (SLE) panel.
Secondary Outcome Measures
Part A: Change From Baseline in Peripheral Blood Platelet Count at Part A End of Treatment (A-EOT)
Change from baseline in peripheral blood platelet count at A-EOT will be assessed.
Part A: Change From Baseline in Peripheral Blood Platelet Count during BIVV009 Treatment
Change from baseline in peripheral blood platelet count during BIVV009 treatment will be assessed.
Part A: Number of Participants who are independent from using combination Immune Thrombocytopenia (ITP) therapy during A-EOT but receive combination ITP therapy after A-EOT
Number of participants who are independent from using combination ITP therapy during A-EOT but receive combination ITP therapy after A-EOT will be assessed.
Part A: Number of Participants who Achieve Complete Response Through A-EOT
Complete response (CR) is defined as a platelet count greater than or equal to (>=) 100*10^9/liter (L) measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
Part A: Number of Participants who Achieve Response Through A-EOT
Response or Better: Response (R) is defined as a platelet count >= 30*10^9/L and a greater than 2-fold increase from baseline measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits; and CR: A platelet count >=100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
Part A: Duration of Complete Response per Each CR
Duration of CR is defined as the number of consecutive days in which a patient's peripheral blood platelet count is >= 100*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
Part A: Duration of Response per Each Response
Duration of response is defined as the number of consecutive days in which a patient's peripheral blood platelet count is >= 30*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
Part A: Time to First Platelet Response
Time to first platelet response is defined as greater than or equal to 30*10^9/L, 50*10^9/L, 100*10^9/L (confirmed by a consecutive platelet response at least 7 days apart).
Part A: Number of Participants who Report Loss of Response Among Those who Achieve Response
Number of participants who report loss of response among those who achieve response will be reported. For a participant with a response (R), the loss of the response is defined as a platelet count < 30*10^9/L measured on 2 consecutive occasions at least 1 day apart, or a less than 2-fold increase in platelet count from baseline measured on 2 consecutive occasions at least 1 day apart, or the presence of bleeding, or use of the combination ITP therapy.
Part A: Number of Participants who Report Loss of Complete Response Among Those who Achieve Complete Response
Number of participants who report loss of complete response among those who achieve complete response will be reported. For a participant with a complete response (CR), loss of complete response is defined as a platelet count less than (<) 100*10^9/L measured on 2 consecutive occasions more than 1 day apart and/or the presence of bleeding or use of the combination ITP therapy.
Part B: Change From Baseline in Peripheral Blood Platelet Count to B-EOT
Change from baseline (Part B) in peripheral blood platelet count to B-EOT will be assessed.
Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy During Treatment Period
Number of participants who achieve CR and the lack of platelet transfusions or other ITP therapy during Part B treatment period will be reported. Complete response (CR): A platelet count >= 100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
Part B: Number of Participants who Achieve Response Through Part B End of Treatment (B-EOT)
Number of participants who achieve response through B-EOT will be reported.
Part B: Duration of Complete Response per Each CR
Duration of CR is defined as the number of consecutive days in which a participant's peripheral blood platelet count is >= 100*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
Part B: Duration of Response per each Response
Duration of response is defined as the number of consecutive days in which a participant's peripheral blood platelet count is >= 30*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
Part B: Number of Participants who achieve a platelet count >= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT
Number of participants who achieve a platelet count >= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT will be assessed.
Part B: Number of Participants who achieve a platelet count >=30*10^9/L, a >2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart, have absence of bleeding on and through these two visits, use any combination ITP therapy
Number of participants who achieve a platelet count >= 30*10^9/L and a greater than (>) 2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT will be assessed.
Part B: Number of Participants who do not Require Other Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Part B Treatment Period
Number of Participants who do not require other ITP therapy (non-transfusion) following the last BIVV009 dose will be assessed.
Part B: Number of Participants who do not Require Platelet Transfusions During the Part B Treatment Period
Number of Participants who do not require platelet transfusions during the Part B treatment period will be reported.
Part B: Number of Participants who Experience any Bleeding Episode, Bleeding by Grade or Serious Bleeding
Number of participants who experience any bleeding episode, bleeding by grade or serious bleeding according to the International Working Group (IWG) Bleeding Assessment Tool (BAT) will be reported.
Plasma Concentrations of BIVV009
Plasma concentrations of BIVV009 will be assessed.
Maximum Observed Plasma Concentration (Cmax) of BIVV009
Maximum observed concentration of BIVV009 in plasma will be assessed.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009 will be assessed.
Area Under the Concentration-time Curve (AUC) From Hour 0 to the last quantifiable time point (AUC [0-t]) of BIVV009
AUC (0-t) is the area under the Concentration-time curve (AUC) from hour 0 to the last quantifiable time point of BIVV009.
Number of Participants With Anti-drug antibodies (ADAs) Against BIVV009
Blood samples will be collected to determine number of participants with anti-drug antibodies (ADAs) against BIVV009.
Complement System Classical Pathway Levels as Measured by WIESLAB Assay
Inhibition by BIVV009 of the complement system classical pathway measured by the WIESLAB assay.
Total Complement (CH50) Levels
Complement CH50 is a blood test that helps us determine whether protein abnormalities and deficiencies in the complement system are responsible for any increase in autoimmune activity. It will be assessed using complement assays.
Total Complement Factor C4 Levels
Total C4 Levels will be assessed in plasma using complement assays.
C1 Complex Components: C1q
C1q Levels will be assessed in plasma using complement assays.
Thrombopoietin Level
Thrombopoietin level will be assessed in plasma using complement assays.
Full Information
NCT ID
NCT03275454
First Posted
September 5, 2017
Last Updated
May 16, 2023
Sponsor
Bioverativ, a Sanofi company
1. Study Identification
Unique Protocol Identification Number
NCT03275454
Brief Title
A Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple- Dose BIVV009 in Participants With Chronic Immune Thrombocytopenia (ITP)
Official Title
A Phase 1 Safety, Tolerability, and Pharmacokinetics & Pharmacodynamics Study of Multiple- Dose BIVV009 in Patients With Chronic Immune Thrombocytopenia (ITP)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
August 14, 2017 (Actual)
Primary Completion Date
February 16, 2021 (Actual)
Study Completion Date
February 16, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioverativ, a Sanofi company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to explore the safety, preliminary clinical benefit, and activity of BIVV009 in patients with chronic immune thrombocytopenia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Purpura, Thrombocytopenic, Idiopathic
Keywords
Autoimmune Diseases, Hematologic Diseases, Immune System Diseases, Blood Platelet Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BIVV009
Arm Type
Experimental
Arm Description
Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009 intravenous (IV) infusion and participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009 every 2 weeks for approximately 21 weeks in Part A (based on time to complete 11 doses of study drug). There will be a 9-week safety follow-up/washout period after administration of the last dose of study drug in Part A. Participants who have been shown to benefit from BIVV009 treatment during Part A, will receive BIVV009 (based on weight) biweekly for up to 52 weeks of BIVV009 after Last Patient In (LPI) in part B.
Intervention Type
Drug
Intervention Name(s)
BIVV009 6.5 grams
Intervention Description
Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009.
Intervention Type
Drug
Intervention Name(s)
BIVV009 7.5 grams
Intervention Description
Participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. A serious adverse event (SAE) is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Time Frame
Up to 97 weeks
Title
Number of Participants With Premature Study Terminations
Description
Number of participants with premature study terminations will be assessed.
Time Frame
Approximately 97 weeks
Title
Number of Participants With Clinical Laboratory Abnormalities
Description
Clinical laboratory abnormalities including one or more specific target-organs for toxicity of BIVV009, abnormalities in D-dimer, thrombin-anti-thrombin assay, and Systemic Lupus Erythematosus (SLE) panel.
Time Frame
Approximately 97 weeks
Secondary Outcome Measure Information:
Title
Part A: Change From Baseline in Peripheral Blood Platelet Count at Part A End of Treatment (A-EOT)
Description
Change from baseline in peripheral blood platelet count at A-EOT will be assessed.
Time Frame
Baseline and A-EOT (Day 147)
Title
Part A: Change From Baseline in Peripheral Blood Platelet Count during BIVV009 Treatment
Description
Change from baseline in peripheral blood platelet count during BIVV009 treatment will be assessed.
Time Frame
Baseline up to Day 147
Title
Part A: Number of Participants who are independent from using combination Immune Thrombocytopenia (ITP) therapy during A-EOT but receive combination ITP therapy after A-EOT
Description
Number of participants who are independent from using combination ITP therapy during A-EOT but receive combination ITP therapy after A-EOT will be assessed.
Time Frame
Day 147 (A-EOT) up to Day 196 (EOS)
Title
Part A: Number of Participants who Achieve Complete Response Through A-EOT
Description
Complete response (CR) is defined as a platelet count greater than or equal to (>=) 100*10^9/liter (L) measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
Time Frame
Up to Day 147
Title
Part A: Number of Participants who Achieve Response Through A-EOT
Description
Response or Better: Response (R) is defined as a platelet count >= 30*10^9/L and a greater than 2-fold increase from baseline measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits; and CR: A platelet count >=100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
Time Frame
Up to Day 147
Title
Part A: Duration of Complete Response per Each CR
Description
Duration of CR is defined as the number of consecutive days in which a patient's peripheral blood platelet count is >= 100*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
Time Frame
Up to Day 196
Title
Part A: Duration of Response per Each Response
Description
Duration of response is defined as the number of consecutive days in which a patient's peripheral blood platelet count is >= 30*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
Time Frame
Up to Day 196
Title
Part A: Time to First Platelet Response
Description
Time to first platelet response is defined as greater than or equal to 30*10^9/L, 50*10^9/L, 100*10^9/L (confirmed by a consecutive platelet response at least 7 days apart).
Time Frame
Up to Day 196
Title
Part A: Number of Participants who Report Loss of Response Among Those who Achieve Response
Description
Number of participants who report loss of response among those who achieve response will be reported. For a participant with a response (R), the loss of the response is defined as a platelet count < 30*10^9/L measured on 2 consecutive occasions at least 1 day apart, or a less than 2-fold increase in platelet count from baseline measured on 2 consecutive occasions at least 1 day apart, or the presence of bleeding, or use of the combination ITP therapy.
Time Frame
Up to Day 196
Title
Part A: Number of Participants who Report Loss of Complete Response Among Those who Achieve Complete Response
Description
Number of participants who report loss of complete response among those who achieve complete response will be reported. For a participant with a complete response (CR), loss of complete response is defined as a platelet count less than (<) 100*10^9/L measured on 2 consecutive occasions more than 1 day apart and/or the presence of bleeding or use of the combination ITP therapy.
Time Frame
Up to Day 196
Title
Part B: Change From Baseline in Peripheral Blood Platelet Count to B-EOT
Description
Change from baseline (Part B) in peripheral blood platelet count to B-EOT will be assessed.
Time Frame
Baseline up to 52 weeks
Title
Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy During Treatment Period
Description
Number of participants who achieve CR and the lack of platelet transfusions or other ITP therapy during Part B treatment period will be reported. Complete response (CR): A platelet count >= 100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding on and through these two visits and the lack of combination ITP therapy on and through these two visits.
Time Frame
Up to 52 weeks
Title
Part B: Number of Participants who Achieve Response Through Part B End of Treatment (B-EOT)
Description
Number of participants who achieve response through B-EOT will be reported.
Time Frame
Up to 52 weeks
Title
Part B: Duration of Complete Response per Each CR
Description
Duration of CR is defined as the number of consecutive days in which a participant's peripheral blood platelet count is >= 100*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
Time Frame
Up to 52 weeks
Title
Part B: Duration of Response per each Response
Description
Duration of response is defined as the number of consecutive days in which a participant's peripheral blood platelet count is >= 30*10^9/L and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.
Time Frame
Up to 52 weeks
Title
Part B: Number of Participants who achieve a platelet count >= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT
Description
Number of participants who achieve a platelet count >= 100*10^9/L on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT will be assessed.
Time Frame
Up to 52 weeks
Title
Part B: Number of Participants who achieve a platelet count >=30*10^9/L, a >2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart, have absence of bleeding on and through these two visits, use any combination ITP therapy
Description
Number of participants who achieve a platelet count >= 30*10^9/L and a greater than (>) 2-fold increase from baseline measured on 2 consecutive occasions at least 7 days apart and have the absence of bleeding on and through these two visits and use any combination ITP therapy through B-EOT will be assessed.
Time Frame
Up to 52 weeks
Title
Part B: Number of Participants who do not Require Other Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Part B Treatment Period
Description
Number of Participants who do not require other ITP therapy (non-transfusion) following the last BIVV009 dose will be assessed.
Time Frame
Up to 52 weeks
Title
Part B: Number of Participants who do not Require Platelet Transfusions During the Part B Treatment Period
Description
Number of Participants who do not require platelet transfusions during the Part B treatment period will be reported.
Time Frame
Up to 52 weeks
Title
Part B: Number of Participants who Experience any Bleeding Episode, Bleeding by Grade or Serious Bleeding
Description
Number of participants who experience any bleeding episode, bleeding by grade or serious bleeding according to the International Working Group (IWG) Bleeding Assessment Tool (BAT) will be reported.
Time Frame
Up to 52 weeks
Title
Plasma Concentrations of BIVV009
Description
Plasma concentrations of BIVV009 will be assessed.
Time Frame
Approximately 97 weeks
Title
Maximum Observed Plasma Concentration (Cmax) of BIVV009
Description
Maximum observed concentration of BIVV009 in plasma will be assessed.
Time Frame
Approximately 97 weeks
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009
Description
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009 will be assessed.
Time Frame
Approximately 97 weeks
Title
Area Under the Concentration-time Curve (AUC) From Hour 0 to the last quantifiable time point (AUC [0-t]) of BIVV009
Description
AUC (0-t) is the area under the Concentration-time curve (AUC) from hour 0 to the last quantifiable time point of BIVV009.
Time Frame
Approximately 97 weeks
Title
Number of Participants With Anti-drug antibodies (ADAs) Against BIVV009
Description
Blood samples will be collected to determine number of participants with anti-drug antibodies (ADAs) against BIVV009.
Time Frame
Up to 97 weeks
Title
Complement System Classical Pathway Levels as Measured by WIESLAB Assay
Description
Inhibition by BIVV009 of the complement system classical pathway measured by the WIESLAB assay.
Time Frame
Up to 97 weeks
Title
Total Complement (CH50) Levels
Description
Complement CH50 is a blood test that helps us determine whether protein abnormalities and deficiencies in the complement system are responsible for any increase in autoimmune activity. It will be assessed using complement assays.
Time Frame
Up to 97 weeks
Title
Total Complement Factor C4 Levels
Description
Total C4 Levels will be assessed in plasma using complement assays.
Time Frame
Up to 97 weeks
Title
C1 Complex Components: C1q
Description
C1q Levels will be assessed in plasma using complement assays.
Time Frame
Up to 97 weeks
Title
Thrombopoietin Level
Description
Thrombopoietin level will be assessed in plasma using complement assays.
Time Frame
Up to 97 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Part A:
Chronic immune thrombocytopenia (ITP) (ITP lasting for greater than or equal to ([>=] 12 months) as defined in the protocol
Normal prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT)
No history of a coagulation disorder
Hemoglobin level greater than (>) 10 gram per deciliter (g/dL) (following blood transfusion is acceptable) and normal white blood cell (WBC) and neutrophil counts (elevated WBC/absolute neutrophil count [ANC] attributed to steroid treatment is acceptable)
Eastern Cooperative Oncology Group (ECOG) performance status grade less than or equal to (<=) 2
Documented vaccinations against encapsulated bacterial pathogens (Neisseria meningitis, including serogroup B meningococcus [where available], Haemophilus influenzae, and Streptococcus pneumoniae) within 5 years of enrollment
Adequate intravenous (IV) access
Part B:
Able to comprehend and to give informed consent for Part B
History of ITP and previously treated with at least 1 dose of BIVV009 in Part A
Evidence of treatment efficacy to BIVV009 as defined by a platelet count > 30*10^9/L on at least 1 occasion OR a doubling of the platelet count from baseline
Participants who have completed the 21-week Part A treatment period but have not reached the Part A End of Study (EOS) visit must have evidence of ongoing or recurrent thrombocytopenia during the Part A safety follow-up/washout period as demonstrated by a platelet count less than (<) 50*10^9/L or a >= 50 percent (%) decrease in platelet count over < 1 week
Exclusion Criteria:
Part A:
Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the participant or compromise the quality of the data derived from his/her participation in this study
Clinically relevant infection of any kind within the preceding month of enrollment
History of venous or arterial thrombosis within the preceding year of enrollment
Use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or anticoagulants within 1 week of enrollment
Clinical diagnosis of systemic lupus erythematosus (SLE) or other active autoimmune disorders associated with anti-nuclear antibodies (ANAs) including those that are medically controlled, at Screening (other than ITP)
Secondary immune thrombocytopenia from any cause including lymphoma, chronic lymphocytic leukemia, and drug-induced thrombocytopenia
Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening
Positive human immunodeficiency virus (HIV) test result prior to or at Screening
Part B:
Presence of unacceptable side effects or toxicity associated with BIVV009 (including prior hypersensitivity reactions to BIVV009) such that there is an unfavorable risk-benefit assessment for continued treatment with BIVV009 in the opinion of the Investigator and/or Sponsor
For participants who have completed the 9-week safety follow-up/washout period and final study visit before entry into Part B, a positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening. Patients who have undergone hepatitis C antiviral therapy may be allowed if they are documented to be negative for hepatitis C virus ribonucleic acid (RNA) on at least 2 occasions separated by at least 3 months (including 1 RNA test at least 6 months after completion of antiviral therapy) and are also negative for hepatitis C virus RNA at Screening
Use of prescribed or over-the-counter medications, supplements, vitamins, and/or herbal remedies within 2 weeks before the first dose of BIVV009 in Part B, which in the judgment of the Investigator may adversely affect the participants welfare or the integrity of the study results (excluding hormonal contraception in female participants)
If previously treated with rituximab, the last dose of rituximab was administered < 12 weeks before the first dose of BIVV009 in Part B
Clinical diagnosis of systemic lupus erythematosus (SLE) or other active autoimmune disorders associated with anti-nuclear antibodies (ANA), including those that are medically controlled, at Screening (other than ITP). Positive ANAs at screening that are not associated with an autoimmune disorder (other than ITP) may be allowed if present for >= 28 days without associated clinically relevant symptoms
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Georgetown Lombardi Comprehensive Cancer Center
City
Georgetown
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Facility Name
Massachusetts General Hospital - Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02144
Country
United States
Facility Name
University of Pittsburgh Medical Center (UPMC) Hilman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Essen University Hospital Department of Hematology
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
University College Hospital
City
London
ZIP/Postal Code
WC1E 6HX
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
35973190
Citation
Broome CM, Roth A, Kuter DJ, Scully M, Smith R, Wang J, Reuter C, Hobbs W, Daak A. Safety and efficacy of classical complement pathway inhibition with sutimlimab in chronic immune thrombocytopenia. Blood Adv. 2023 Mar 28;7(6):987-996. doi: 10.1182/bloodadvances.2021006864.
Results Reference
result
Learn more about this trial
A Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple- Dose BIVV009 in Participants With Chronic Immune Thrombocytopenia (ITP)
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