A Phase 2a Study Evaluating BIVV020 in Adults With Persistent/Chronic Immune Thrombocytopenia (ITP)

A Multicenter, Phase 2a, Open-label, Non-randomized Study Evaluating the Efficacy, Safety, and Tolerability of BIVV020 in Adults With Persistent/Chronic Immune Thrombocytopenia (ITP)

Primary Objective:

- To evaluate the effect of BIVV020 on the durability of platelet response in participants with persistent/chronic immune thrombocytopenia (ITP)

Secondary Objectives:

• To assess the safety and tolerability of BIVV020
• To assess the pharmacokinetics of BIVV020
• To assess the response rate of treatment with BIVV020
• To assess the time to response
• To assess the effect of treatment with BIVV020 on the requirement for rescue ITP therapy
• To assess the immunogenicity of BIVV020

Study Overview

• Status: Completed
• Conditions: Immune Thrombocytopenia (ITP)
• Intervention / Treatment: Drug: SAR445088 (BIVV020)

Detailed Description

Study duration:

• Screening period: up to 56 days
• Transition period between last sutimlimab dose and first dose of BIVV020 (for participants who were previously receiving sutimlimab): 14 days, included as part of the 56-day Screening period. Treatment duration: Minimum 52 weeks.

Visit frequency:

• Day 1
• Day 4
• Weeks 1 to 6: Weekly
• Weeks 7 to 12: Every other week
• Weeks 13 to 24: Every 4 weeks
• Weeks 25+: At least every 8 weeks
• End of Study visit: 22 weeks after the last dose of BIVV020

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Ostrava - Poruba, Czechia, 70852
    • Investigational Site Number :2030002
• Germany
  • Essen, Germany, 45147
    • Investigational Site Number :2760001
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Investigational Site Number :5280001
• Spain
  • Palma de Mallorca, Spain, 07120
    • Investigational Site Number :7240001
  • Sevilla, Spain, 41013
    • Investigational Site Number :7240003
  • A Coruña [La Coruña]
    • La Coruña, A Coruña [La Coruña], Spain, 15006
      • Investigational Site Number :7240002
• United Kingdom
  • London, City Of
    • London, London, City Of, United Kingdom, W12 0HS
      • Investigational Site Number :8260002
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Investigational Site Number :8400001
  • Florida
    • Tamarac, Florida, United States, 33321
      • Investigational Site Number :8400002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria :

• Male and female participants ≥18 years of age at the time of signing the informed consent
• Confirmed diagnosis of primary ITP; for participants who previously received sutimlimab in study TDR16218 (NCT03275454), a response to sutimlimab must have been obtained, as defined by platelet count ≥30 × 10^9/L on 2 visits at least 7 days apart

• For participants who have not previously received sutimlimab: persistent/chronic ITP (ITP lasting for ≥6 months) and all the following conditions:

  1. Platelet count ≤30 × 10^9/L on 2 occasions at least 5 days apart during the Screening Period;
  2. Lack of an adequate platelet count response (as defined by maintenance of sustained platelet count ≥30 × 109/L in the absence of bleeding) to at least 2 ITP treatments, 1 of which was a thrombopoietin receptor agonist. Other ITP treatments include: IVIg, anti-D immunoglobulin, corticosteroids, splenectomy, rituximab, cyclophosphamide, azathioprine, danazol, cyclosporin A, mycophenolate mofetil, or fostamatinib.
  3. If receiving weekly thrombopoietin receptor agonist dosing, the last dose must have been administered ≥7 days before the first dose of BIVV020. If receiving daily thrombopoietin receptor agonist dosing, the last dose must have been administered ≥24 hours before the first dose of BIVV020
  4. If applicable, concurrent administration of ITP medications (eg. corticosteroids, IVIg, azathioprine, danazol, cyclosporin A, mycophenolate mofetil, or thrombopoietin receptor agonists) is acceptable provided the participant has been on a stable dose for at least 1 month.
  5. If previously dosed with rituximab, the last dose of rituximab must have been administered at least 12 weeks before the first dose of BIVV020
• Documented vaccinations against encapsulated bacterial pathogens (Neisseria meningitidis, including serogroup B where available, Haemophilus influenzae, and Streptococcus pneumoniae) within 5 years of enrollment
• Contraceptive use for women of childbearing potential and men who were sexually active with a female partner of childbearing potential

Exclusion criteria:

Participants were excluded from the study if any of the following criteria apply:

• 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 the study
• Clinical diagnosis of SLE
• Clinically relevant infection within the month prior to enrollment
• History of venous or arterial thrombosis within the year prior to enrollment
• Secondary ITP from any cause including lymphoma, chronic lymphocytic leukemia, and drug-induced thrombocytopenia
• Positive hepatitis B surface antigen (HBsAg) or active HCV infection
• HIV infection
• Pregnant or lactating women
• Hemoglobin level <10 g/dL

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR445088; Participants received SAR445088 (BIVV020).	Drug: SAR445088 (BIVV020); Pharmaceutical form:solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Durable Platelet Response	A naive participant was a participant who did not use sutimlimab prior to enrollment. A switcher was a participant who used sutimlimab prior to enrollment. A naive participant was a responder if the platelet count was >=50 × 10^9/liter (L) at >=50 percent (%) of scheduled visits, or for participants with baseline platelet count <15 × 10^9/L, a >=20 × 10^9/L increase in platelet count from baseline at >=50% of scheduled visits, without receiving rescue immune thrombocytopenia (ITP) therapy. A switcher was a responder if the maintenance platelet count was >=30 × 10^9/L at >=50% of scheduled visits, without receiving rescue ITP therapy.	From Week 3 to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (SAE)	An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that developed after the first study treatment administration in the safety analysis period which was defined as the period from the first study intervention administration to the end of study (EOS) visit (up to Week 103).	From first study treatment administration (Day 1) up to Week 103
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematology	Criteria for potentially clinically significant laboratory abnormalities (PCSA): White blood cells: less than (<)3.0 Giga/L (Non-Black [NB]) or <2.0 Giga/L (Black [B]), greater than or equal to (>=)16.0 Giga/L; Lymphocytes: greater than (>)4.0 Giga/L; Neutrophils: <1.5 Giga/L (NB) or <1.0 Giga/L (B); Monocytes: >0.7 Giga/L; Basophils: >0.1 Giga/L; Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L); Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L) (Male[M]) or <=95 g/L (Female[F]), >=185 g/L (M) or >=165 g/L (F), Decrease from baseline (DFB) >=20 g/L; Hematocrit: <=0.37 volume/volume (v/v) (M) or <=0.32 v/v (F); Red blood cells (RBC): >=6 Tera/L; Platelets:<100 Giga/L, >=700 Giga/L. Only the worst case during the treatment-emergent (TE) period for each participant with worsening from baseline is presented.	On Days 1, 15, 29, at Weeks 8, 12, 24, and then every 8 weeks until the end of study (EOS) (Week 103)
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Clinical Chemistry	Criteria for PCSA: Blood Urea Nitrogen: >=17 millimole (mmol)/L; Creatinine: >=150 micromole (mcmol)/L (Adults), >=30% and <100% change from baseline, >=100% change from baseline; Potassium: <3 mmol/L, >=5.5 mmol/L; Sodium: <=129 mmol/L, >=160 mmol/L; Aspartate Aminotransferase (AST): >3 ULN, >5 ULN, >10 ULN, >20 ULN; Alanine Aminotransferase (ALT): >3 ULN, >5 ULN, >10 ULN, >20 ULN; Alkaline Phosphatase (ALP): >1.5 ULN; Bilirubin: >1.5 ULN, >2 ULN; ALT and Total Bilirubin: ALT >3 ULN and TBILI >2 ULN. Only the worst case during the TE period for each participant with worsening from baseline is presented.	On Days 1, 15, 29, Weeks 8, 12 and 24, then every 8 weeks until the EOS (Week 103)
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Coagulation	The number of participants with PCSA for coagulation parameters during the TE period without PCSA definition by biological function are presented. The parameters evaluated were prothrombin time, prothrombin international normalized ratio and activated partial thromboplastin time (APTT).	On Days 1, 15, 29, Weeks 8, 12 and 24, then every 8 weeks until the EOS (Week 103)
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Urinalysis	Criteria for PCSA: potential of Hydrogen (pH) <=4.6, >=8. Only the worst case during the TE period for each participant with worsening from baseline is presented.	On Days 1, 15, 29, Weeks 8, 12 and 24, then every 8 weeks until the EOS (Week 103)
Plasma Concentrations of SAR445088 (BIVV020)	Plasma samples were collected at specified timepoints.	1-hour post-dose on Day 1, on Days 8, 15, 29, 43, at Weeks 12, 16, 24, 32, 40, 48, 56, 64, 72, 80 and EOS visit, up to 103 weeks
Number of Responders to SAR445088 (BIVV020)	A participant was a responder if the platelet count was >=50 × 10^9/L and there was a greater than 2-fold increase from baseline, measured on 2 occasions at least 7 days apart with the absence of bleeding [bleeding score >=2 on the World Health Organization (WHO) bleeding scale] while the platelet counts were maintained above the threshold and lack of combination ITP therapy during this period. WHO bleeding scores: 1=Petechiae; 2=Mild blood loss; 3=Gross blood loss; and 4=Debilitating blood loss.	At Weeks 24 and 56
Time to First Platelet Response	Time to first platelet response was defined as greater than or equal to each of the following values: 50 × 10^9/L or 100 × 10^9/L (confirmed by 2 measurements at least 7 days apart). It was calculated as date of first occurrence of confirmed platelet count response before rescue therapy.	From Baseline (Day 1) up to Week 56
Percentage of Participants Who Did Not Require Rescue Therapy for an Acute Episode of Thrombocytopenia After Week 3	Data was collected to assess the effect of treatment with SAR445088 (BIVV020) on the requirement for rescue ITP therapy.	Up to Week 84
Number of Participants With Anti-Drug Antibody (ADAs) Response to SAR445088 (BIVV020)	Plasma samples were analyzed for the presence of ADAs for SAR445088 (BIVV020) using validated assays. Treatment-induced ADA was defined as ADAs that developed during the treatment-emergent period and without pre-existing ADA. Pre-existing ADA was defined as ADAs present in samples drawn before first study treatment administration. Treatment-boosted ADA positive was defined as pre-existing ADA (i.e., ADA positive at baseline) that was boosted at least a 9-fold increase of titer values during the treatment-emergent period than the baseline. Treatment-emergent ADA positive was defined as either treatment-induced ADA positive or treatment-boosted ADA positive during the treatment-emergent period. Inconclusive ADA was defined as the one that could not irrefutably be classified as with or without treatment-emergent ADA.	Up to Week 103

Collaborators and Investigators

• Sponsor: Bioverativ, a Sanofi company
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2021
• Primary Completion (Actual): February 15, 2022
• Study Completion (Actual): February 7, 2023

Study Registration Dates

• First Submitted: December 9, 2020
• First Submitted That Met QC Criteria: December 9, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: PDY16894; 2020-004162-18 (EudraCT Number); U1111-1253-2343 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No