Clinical trial NCT03275454: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Purpura, Thrombocytopenic, Idiopathic
Keywords: Autoimmune Diseases
Hematologic Diseases
Immune System Diseases
Blood Platelet Disorders
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-09-07
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Up to 97 weeks
measure: Number of Participants With Premature Study Terminations
timeFrame: Approximately 97 weeks
measure: Number of Participants With Clinical Laboratory Abnormalities
timeFrame: Approximately 97 weeks
Secondary outcomes:
measure: Part A: Change From Baseline in Peripheral Blood Platelet Count at Part A End of Treatment (A-EOT)
timeFrame: Baseline and A-EOT (Day 147)
measure: Part A: Change From Baseline in Peripheral Blood Platelet Count during BIVV009 Treatment
timeFrame: Baseline up to Day 147
measure: 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
timeFrame: Day 147 (A-EOT) up to Day 196 (EOS)
measure: Part A: Number of Participants who Achieve Complete Response Through A-EOT
timeFrame: Up to Day 147
measure: Part A: Number of Participants who Achieve Response Through A-EOT
timeFrame: Up to Day 147
measure: Part A: Duration of Complete Response per Each CR
timeFrame: Up to Day 196
measure: Part A: Duration of Response per Each Response
timeFrame: Up to Day 196
measure: Part A: Time to First Platelet Response
timeFrame: Up to Day 196
measure: Part A: Number of Participants who Report Loss of Response Among Those who Achieve Response
timeFrame: Up to Day 196
measure: Part A: Number of Participants who Report Loss of Complete Response Among Those who Achieve Complete Response
timeFrame: Up to Day 196
measure: Part B: Change From Baseline in Peripheral Blood Platelet Count to B-EOT
timeFrame: Baseline up to 52 weeks
measure: Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy During Treatment Period
timeFrame: Up to 52 weeks
measure: Part B: Number of Participants who Achieve Response Through Part B End of Treatment (B-EOT)
timeFrame: Up to 52 weeks
measure: Part B: Duration of Complete Response per Each CR
timeFrame: Up to 52 weeks
measure: Part B: Duration of Response per each Response
timeFrame: Up to 52 weeks
measure: 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
timeFrame: Up to 52 weeks
measure: 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
timeFrame: Up to 52 weeks
measure: Part B: Number of Participants who do not Require Other Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Part B Treatment Period
timeFrame: Up to 52 weeks
measure: Part B: Number of Participants who do not Require Platelet Transfusions During the Part B Treatment Period
timeFrame: Up to 52 weeks
measure: Part B: Number of Participants who Experience any Bleeding Episode, Bleeding by Grade or Serious Bleeding
timeFrame: Up to 52 weeks
measure: Plasma Concentrations of BIVV009
timeFrame: Approximately 97 weeks
measure: Maximum Observed Plasma Concentration (Cmax) of BIVV009
timeFrame: Approximately 97 weeks
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009
timeFrame: Approximately 97 weeks
measure: Area Under the Concentration-time Curve (AUC) From Hour 0 to the last quantifiable time point (AUC [0-t]) of BIVV009
timeFrame: Approximately 97 weeks
measure: Number of Participants With Anti-drug antibodies (ADAs) Against BIVV009
timeFrame: Up to 97 weeks
measure: Complement System Classical Pathway Levels as Measured by WIESLAB Assay
timeFrame: Up to 97 weeks
measure: Total Complement (CH50) Levels
timeFrame: Up to 97 weeks
measure: Total Complement Factor C4 Levels
timeFrame: Up to 97 weeks
measure: C1 Complex Components: C1q
timeFrame: Up to 97 weeks
measure: Thrombopoietin Level
timeFrame: Up to 97 weeks
Other outcomes:
Locations:
city: Georgetown
country: United States
facility: Georgetown Lombardi Comprehensive Cancer Center
state: District of Columbia
city: Boston
country: United States
facility: Massachusetts General Hospital - Cancer Center
state: Massachusetts
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC) Hilman Cancer Center
state: Pennsylvania
city: Essen
country: Germany
facility: Essen University Hospital Department of Hematology
city: London
country: United Kingdom
facility: University College Hospital
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
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.