A Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple- Dose BIVV009 in Participants With Chronic Immune Thrombocytopenia (ITP)

A Phase 1 Safety, Tolerability, and Pharmacokinetics & Pharmacodynamics Study of Multiple- Dose BIVV009 in Patients With Chronic Immune Thrombocytopenia (ITP)

Sponsors

Lead Sponsor: Bioverativ, a Sanofi company

Source Sanofi
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.

Overall Status Completed
Start Date 2017-08-14
Completion Date 2021-02-16
Primary Completion Date 2021-02-16
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Incidence of Treatment-Emergent Adverse Events Up to 97 weeks
Number of Participants With Premature Study Terminations Approximately 97 weeks
Number of Participants With Clinical Laboratory Abnormalities Approximately 97 weeks
Secondary Outcome
Measure Time Frame
Part A: Change From Baseline in Peripheral Blood Platelet Count at Part A End of Treatment (A-EOT) Baseline and A-EOT (Day 147)
Part A: Change From Baseline in Peripheral Blood Platelet Count during BIVV009 Treatment Baseline up to Day 147
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 Day 147 (A-EOT) up to Day 196 (EOS)
Part A: Number of Participants who Achieve Complete Response Through A-EOT Up to Day 147
Part A: Number of Participants who Achieve Response Through A-EOT Up to Day 147
Part A: Duration of Complete Response per Each CR Up to Day 196
Part A: Duration of Response per Each Response Up to Day 196
Part A: Time to First Platelet Response Up to Day 196
Part A: Number of Participants who Report Loss of Response Among Those who Achieve Response Up to Day 196
Part A: Number of Participants who Report Loss of Complete Response Among Those who Achieve Complete Response Up to Day 196
Part B: Change From Baseline in Peripheral Blood Platelet Count to B-EOT Baseline up to 52 weeks
Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy During Treatment Period Up to 52 weeks
Part B: Number of Participants who Achieve Response Through Part B End of Treatment (B-EOT) Up to 52 weeks
Part B: Duration of Complete Response per Each CR Up to 52 weeks
Part B: Duration of Response per each Response Up to 52 weeks
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 Up to 52 weeks
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 Up to 52 weeks
Part B: Number of Participants who do not Require Other Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Part B Treatment Period Up to 52 weeks
Part B: Number of Participants who do not Require Platelet Transfusions During the Part B Treatment Period Up to 52 weeks
Part B: Number of Participants who Experience any Bleeding Episode, Bleeding by Grade or Serious Bleeding Up to 52 weeks
Plasma Concentrations of BIVV009 Approximately 97 weeks
Maximum Observed Plasma Concentration (Cmax) of BIVV009 Approximately 97 weeks
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009 Approximately 97 weeks
Area Under the Concentration-time Curve (AUC) From Hour 0 to the last quantifiable time point (AUC [0-t]) of BIVV009 Approximately 97 weeks
Number of Participants With Anti-drug antibodies (ADAs) Against BIVV009 Up to 97 weeks
Complement System Classical Pathway Levels as Measured by WIESLAB Assay Up to 97 weeks
Total Complement (CH50) Levels Up to 97 weeks
Total Complement Factor C4 Levels Up to 97 weeks
C1 Complex Components: C1q Up to 97 weeks
Thrombopoietin Level Up to 97 weeks
Enrollment 12
Condition
Intervention

Intervention Type: Drug

Intervention Name: BIVV009 6.5 grams

Description: Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009.

Arm Group Label: BIVV009

Intervention Type: Drug

Intervention Name: BIVV009 7.5 grams

Description: Participants who weigh 75 kg or more will receive fixed doses of 7.5 grams of BIVV009.

Arm Group Label: BIVV009

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Clinical Sciences & Operations Study Director Sanofi
Location
Facility:
Georgetown Lombardi Comprehensive Cancer Center | Georgetown, District of Columbia, 20057, United States
Massachusetts General Hospital - Cancer Center | Boston, Massachusetts, 02144, United States
University of Pittsburgh Medical Center (UPMC) Hilman Cancer Center | Pittsburgh, Pennsylvania, 15232, United States
Essen University Hospital Department of Hematology | Essen, 45147, Germany
University College Hospital | London, WC1E 6HX, United Kingdom
Location Countries

Germany

United Kingdom

United States

Verification Date

2021-03-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: BIVV009

Type: Experimental

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.

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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