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Trial record 30 of 42 for:    Recruiting Studies | ITP

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

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ClinicalTrials.gov Identifier: NCT03275454
Recruitment Status : Recruiting
First Posted : September 7, 2017
Last Update Posted : September 28, 2018
Sponsor:
Information provided by (Responsible Party):
Bioverativ Therapeutics Inc. ( 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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
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 8, 2017
Estimated Primary Completion Date : October 11, 2019
Estimated Study Completion Date : October 11, 2019


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. 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 during 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 End of Treatment (EOT) [ Time Frame: Baseline and EOT (Day 147) ]
    Change from baseline in peripheral blood platelet count at 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 Require Additional Chronic Immune Thrombocytopenia (ITP) Therapy Following the Last BIVV009 Dose [ Time Frame: Day 147 (EOT) up to Day 196 (EOS) ]
    Number of Participants who require additional ITP therapy following the last BIVV009 dose will be assessed.

  4. Part A: Number of Participants who Achieve Complete Response Based on Best Response Through EOT [ Time Frame: Up to Day 196 ]
    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.

  5. Part A: Number of Participants who Achieve Response or Better Based on Best Response Through EOT [ Time Frame: Up to Day 196 ]
    Response or Better: Response (R) is defined as a platelet count >= 30*10^9/L or a greater than 2-fold increase from baseline measured on 2 occasions at least 7 days apart and the absence of bleeding; and CR: A platelet count >=100*10^9/L measured on 2 occasions at least 7 days apart and the absence of bleeding.

  6. Part A: Duration of Complete Response per Each CR [ Time Frame: Up to Day 196 ]
    Duration of CR as defined as the number of consecutive weeks (> 2) in which a patient's peripheral blood platelet count is >= 100* 109/L divided by the duration of study treatment in weeks (i.e., number of weeks from first dose to the EOT, 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 as defined as the number of consecutive weeks in which a patient's peripheral blood platelet count is >= 30* 109/L divided by the duration of study treatment in weeks (i.e., number of weeks from first dose to EOT, 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 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. Loss of response is defined as a platelet count < 30*10^9/L, or a less than 2-fold increase in platelet count from baseline, or the presence of bleeding. Platelet count must be measured on 2 occasions more than 1 day apart.

  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. Loss of complete response is defined as a platelet count less than (<) 100*10^9/L measured on 2 occasions more than 1 day apart and/or the presence of bleeding.

  11. Part B: Number of Participants who Achieve CR and the Lack of Platelet Transfusions or Other ITP Therapy Based on Best Response 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 based on best response 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.

  12. Part B: Number of Participants who Achieve Response and the Lack of Platelet Transfusions or Other ITP Therapy Based on Best Response During Treatment Period [ Time Frame: Up to 52 weeks ]
    Number of participants who achieve response and the lack of platelet transfusions or other ITP therapy based on best response during Part B treatment period will be reported.

  13. Part B: Duration of Complete Response [ Time Frame: Up to 52 weeks ]
    Duration of CR is defined as the number of consecutive weeks (> 2) in which a participants peripheral blood platelet count is >= 100*10^9/L divided by the duration of study treatment in weeks (i.e., number of weeks from first dose to the EOT, and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.

  14. Part B: Duration of Response [ Time Frame: Up to 52 weeks ]
    Duration of response is defined as the number of consecutive weeks in which a participants peripheral blood platelet count is >= 30*10^9/L divided by the duration of study treatment in weeks (i.e., number of weeks from first dose to EOT, and the absence of bleeding, and the lack of platelet transfusions or other ITP therapy.

  15. Part B: Number of Participants who have Received Combination Therapy and who Achieve Complete Response During the Treatment Period [ Time Frame: Up to 52 weeks ]
    Number of participants who have received combination therapy and who achieve CR during the treatment period as defined by a platelet count >= 100*10^9/L measured at any 2 consecutive, post-baseline study visits at least 7 days apart and the absence of bleeding as defined by the International Working Group (IWG) Bleeding Assessment Tool (BAT) will be determined.

  16. Part B: Number of Participants who have Received Combination Therapy and who Achieve Response During the Treatment Period [ Time Frame: Up to 52 weeks ]
    Number of participants who have received combination therapy and who achieve Response during the treatment period as defined by a platelet count >= 30*10*9/L measured at any 2 consecutive, post-baseline study visits at least 7 days apart and the absence of bleeding as defined by the International Working Group Bleeding Assessment Tool (IWG BAT).

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

  18. Part B: Number of Participants who do not Require Additional Immune Thrombocytopenia (ITP) Therapy (non-transfusion) During the Treatment Period [ Time Frame: Up to 52 weeks ]
    Number of Participants who do not require additional 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 Treatment Period [ Time Frame: Up to 52 weeks ]
    Number of Participants who do not require platelet transfusions during the 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 IWG 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.


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
Contact: Bioverativ - a Sanofi company 1-888-794-1415 clinicaltrials@bioverativ.com

Locations
United States, Washington
Georgetown Lombardi Comprehensive Cancer Center Recruiting
Georgetown, Washington, United States, 20057
Sponsors and Collaborators
Bioverativ - a sanofi company

Responsible Party: Bioverativ - a sanofi company
ClinicalTrials.gov Identifier: NCT03275454     History of Changes
Other Study ID Numbers: BIVV009-201
BIVV009-201 ( Other Identifier: Bioverativ - a Sanofi company )
First Posted: September 7, 2017    Key Record Dates
Last Update Posted: September 28, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bioverativ Therapeutics Inc. ( Bioverativ - a sanofi company ):
Autoimmune Diseases
Hematologic Diseases
Immune System Diseases
Blood Platelet Disorders

Additional relevant MeSH terms:
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