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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03275454
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : April 24, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Bioverativ, a Sanofi company )

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.

Condition or disease Intervention/treatment Phase
Purpura, Thrombocytopenic, Idiopathic Drug: BIVV009 6.5 grams Drug: BIVV009 7.5 grams Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Safety, Tolerability, and Pharmacokinetics & Pharmacodynamics Study of Multiple- Dose BIVV009 in Patients With Chronic Immune Thrombocytopenia (ITP)
Actual Study Start Date : August 14, 2017
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2022


Arm Intervention/treatment
Experimental: BIVV009
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.
Drug: BIVV009 6.5 grams
Participants who weigh less than 75 kilogram (kg) will receive fixed doses of 6.5 grams of BIVV009.

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




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: Up to 97 weeks ]
    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.

  2. Number of Participants With Premature Study Terminations [ Time Frame: Approximately 97 weeks ]
    Number of participants with premature study terminations will be assessed.

  3. Number of Participants With Clinical Laboratory Abnormalities [ Time Frame: Approximately 97 weeks ]
    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 :
  1. Part A: Change From Baseline in Peripheral Blood Platelet Count at Part A End of Treatment (A-EOT) [ Time Frame: Baseline and A-EOT (Day 147) ]
    Change from baseline in peripheral blood platelet count at A-EOT will be assessed.

  2. Part A: Change From Baseline in Peripheral Blood Platelet Count during BIVV009 Treatment [ Time Frame: Baseline up to Day 147 ]
    Change from baseline in peripheral blood platelet count during BIVV009 treatment will be assessed.

  3. 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 [ Time Frame: Day 147 (A-EOT) up to Day 196 (EOS) ]
    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.

  4. Part A: Number of Participants who Achieve Complete Response Through A-EOT [ Time Frame: Up to Day 147 ]
    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.

  5. Part A: Number of Participants who Achieve Response Through A-EOT [ Time Frame: Up to Day 147 ]
    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.

  6. Part A: Duration of Complete Response per Each CR [ Time Frame: Up to Day 196 ]
    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.

  7. Part A: Duration of Response per Each Response [ Time Frame: Up to Day 196 ]
    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.

  8. Part A: Time to First Platelet Response [ Time Frame: Up to Day 196 ]
    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).

  9. Part A: Number of Participants who Report Loss of Response Among Those who Achieve Response [ Time Frame: Up to Day 196 ]
    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.

  10. Part A: Number of Participants who Report Loss of Complete Response Among Those who Achieve Complete Response [ Time Frame: Up to Day 196 ]
    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.

  11. Part B: Change From Baseline in Peripheral Blood Platelet Count to B-EOT [ Time Frame: Baseline up to 52 weeks ]
    Change from baseline (Part B) in peripheral blood platelet count to B-EOT will be assessed.

  12. Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy During Treatment Period [ Time Frame: Up to 52 weeks ]
    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.

  13. Part B: Number of Participants who Achieve Response Through Part B End of Treatment (B-EOT) [ Time Frame: Up to 52 weeks ]
    Number of participants who achieve response through B-EOT will be reported.

  14. Part B: Duration of Complete Response per Each CR [ Time Frame: Up to 52 weeks ]
    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.

  15. Part B: Duration of Response per each Response [ Time Frame: Up to 52 weeks ]
    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.

  16. 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 [ Time Frame: Up to 52 weeks ]
    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.

  17. 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 [ Time Frame: Up to 52 weeks ]
    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.

  18. Part B: Number of Participants who do not Require Other Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Part B Treatment Period [ Time Frame: Up to 52 weeks ]
    Number of Participants who do not require other ITP therapy (non-transfusion) following the last BIVV009 dose will be assessed.

  19. Part B: Number of Participants who do not Require Platelet Transfusions During the Part B Treatment Period [ Time Frame: Up to 52 weeks ]
    Number of Participants who do not require platelet transfusions during the Part B treatment period will be reported.

  20. Part B: Number of Participants who Experience any Bleeding Episode, Bleeding by Grade or Serious Bleeding [ Time Frame: Up to 52 weeks ]
    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.

  21. Plasma Concentrations of BIVV009 [ Time Frame: Approximately 97 weeks ]
    Plasma concentrations of BIVV009 will be assessed.

  22. Maximum Observed Plasma Concentration (Cmax) of BIVV009 [ Time Frame: Approximately 97 weeks ]
    Maximum observed concentration of BIVV009 in plasma will be assessed.

  23. Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009 [ Time Frame: Approximately 97 weeks ]
    Time to Reach Maximum Observed Plasma Concentration (Tmax) of BIVV009 will be assessed.

  24. Area Under the Concentration-time Curve (AUC) From Hour 0 to the last quantifiable time point (AUC [0-t]) of BIVV009 [ Time Frame: Approximately 97 weeks ]
    AUC (0-t) is the area under the Concentration-time curve (AUC) from hour 0 to the last quantifiable time point of BIVV009.

  25. Number of Participants With Anti-drug antibodies (ADAs) Against BIVV009 [ Time Frame: Up to 97 weeks ]
    Blood samples will be collected to determine number of participants with anti-drug antibodies (ADAs) against BIVV009.

  26. Complement System Classical Pathway Levels as Measured by WIESLAB Assay [ Time Frame: Up to 97 weeks ]
    Inhibition by BIVV009 of the complement system classical pathway measured by the WIESLAB assay.

  27. Total Complement (CH50) Levels [ Time Frame: Up to 97 weeks ]
    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.

  28. Total Complement Factor C4 Levels [ Time Frame: Up to 97 weeks ]
    Total C4 Levels will be assessed in plasma using complement assays.

  29. C1 Complex Components: C1q [ Time Frame: Up to 97 weeks ]
    C1q Levels will be assessed in plasma using complement assays.

  30. Thrombopoietin Level [ Time Frame: Up to 97 weeks ]
    Thrombopoietin level will be assessed in plasma using complement assays.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03275454


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 6 Contact-US@sanofi.com

Locations
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United States, District of Columbia
Georgetown Lombardi Comprehensive Cancer Center Recruiting
Georgetown, District of Columbia, United States, 20057
Contact: Helena Jacobs    202-687-4868    Helena.Jacobs@georgetown.edu   
Principal Investigator: Dr. Catherine Broome         
United States, Massachusetts
Massachusetts General Hospital - Cancer Center Recruiting
Boston, Massachusetts, United States, 02144
Principal Investigator: Dr. David Kuter, 617-724-4000, dkuter@mgh.harvard.edu         
United States, Pennsylvania
University of Pittsburgh Medical Center (UPMC) Hilman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Ashley Connor    412-802-8498    connora2@upmc.edu   
Principal Investigator: Dr. Roy Smith         
Germany
Essen University Hospital Department of Hematology Recruiting
Essen, Germany, 45147
Contact: Nicole Preising    +49 201 723 4620    nicole.preising@uk-essen.de   
Principal Investigator: Dr Alexander Roeth, MD         
United Kingdom
University College Hospital Recruiting
London, United Kingdom, WC1E 6HX
Sponsors and Collaborators
Bioverativ, a Sanofi company
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Bioverativ, a Sanofi company
ClinicalTrials.gov Identifier: NCT03275454    
Other Study ID Numbers: TDR16218
BIVV009-201 ( Other Identifier: Bioverativ Therapeutics Inc. )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: April 24, 2020
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sanofi ( Bioverativ, a Sanofi company ):
Autoimmune Diseases
Hematologic Diseases
Immune System Diseases
Blood Platelet Disorders
Additional relevant MeSH terms:
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Thrombocytopenia
Purpura
Purpura, Thrombocytopenic, Idiopathic
Purpura, Thrombocytopenic
Blood Platelet Disorders
Hematologic Diseases
Blood Coagulation Disorders
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Hemorrhagic Disorders
Autoimmune Diseases
Immune System Diseases