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

NCT03275454 | Completed Phase 1 FDA Drug

• 2 other identifiers: TDR16218BIVV009-201
• Study Type: interventional
• Target: 12
• Locations: 3 countries
• Sites: 5

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.

Conditions

Purpura, Thrombocytopenic, Idiopathic

Keywords

Autoimmune Diseases; Hematologic Diseases; Immune System Diseases; Blood Platelet Disorders

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 97 weeks

• Number of Participants With Premature Study Terminations

  Number of participants with premature study terminations will be assessed.

  Approximately 97 weeks

• 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.

  Approximately 97 weeks

Secondary Outcomes (30)

• 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

Study Arms (1)

BIVV009

EXPERIMENTAL

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; Drug: BIVV009 7.5 grams

Interventions

BIVV009 6.5 grams DRUG

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

BIVV009

BIVV009 7.5 grams DRUG

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

BIVV009

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bioverativ, a Sanofi company: lead

Study Sites (5)

Georgetown Lombardi Comprehensive Cancer Center

Georgetown, District of Columbia, 20057, United States

Location

Massachusetts General Hospital - Cancer Center

Boston, Massachusetts, 02144, United States

Location

University of Pittsburgh Medical Center (UPMC) Hilman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Essen University Hospital Department of Hematology

Essen, 45147, Germany

Location

University College Hospital

London, WC1E 6HX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35973190 RESULT

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Autoimmune Diseases; Hematologic Diseases; Immune System Diseases; Blood Platelet Disorders

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Cytopenia; Hemorrhagic Disorders; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 7, 2017
• Study Start: August 14, 2017
• Primary Completion: February 16, 2021
• Study Completion: February 16, 2021
• Last Updated: May 18, 2023

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); US (3); DE (1)