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Trial record 1 of 1 for:    ACT16832
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Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia (wAIHA)

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ClinicalTrials.gov Identifier: NCT04661033
Recruitment Status : Recruiting
First Posted : December 9, 2020
Last Update Posted : October 4, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

-Part A: To evaluate the safety and tolerability of subcutaneous injections of isatuximab in adults with wAIHA Part B: To evaluate the efficacy of the selected dose in adults with wAIHA

Secondary Objective:

  • Part A (Cohorts 2 and 3 only)
  • To evaluate the efficacy of isatuximab in adults with wAIHA
  • To evaluate the durability of response to isatuximab and time to response
  • To evaluate the impact of isatuximab treatment on fatigue Part B
  • To evaluate the safety and tolerability of isatuximab in adults with wAIHA
  • To evaluate the durability of response to isatuximab and time to response
  • To evaluate the impact of isatuximab treatment on fatigue Parts A (all Cohorts) and B
  • To evaluate the effect of isatuximab on markers of hemolysis
  • To characterize the pharmacokinetic profile of isatuximab in adults with wAIHA
  • To evaluate the immunogenicity of isatuximab

Condition or disease Intervention/treatment Phase
Warm Autoimmune Hemolytic Anemia (wAIHA) Drug: Isatuximab SAR650984 Drug: Diphenhydramine Drug: Famotidine Drug: Acetaminophen Drug: Montelukast Phase 1 Phase 2

Detailed Description:
28 weeks (including screening)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Non-randomized, Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Subcutaneous Isatuximab in Adults With Warm Autoimmune Hemolytic Anemia
Actual Study Start Date : September 15, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: Part A/Cohort 1, Part A Cohort/2, Part A/Cohort 3 (optional), Part B
Isatuximab every 2 weeks x 2 doses-Part A/Cohort 1 Isatuximab every 2 weeks x 6 doses-Part A/Cohort 2 Isatuximab every 2 weeks x 6 doses-Part A/Cohort 3 (optional) Isatuximab every 2 weeks x 6 doses-Part B
Drug: Isatuximab SAR650984
Pharmaceutical form:Solution for injection Route of administration: Subcutaneous

Drug: Diphenhydramine
Pharmaceutical form: Tablet Route of administration: Orally

Drug: Famotidine
Pharmaceutical form: Tablet Route of administration: Orally

Drug: Acetaminophen
Pharmaceutical form: Tablet Route of administration: Orally

Drug: Montelukast
Pharmaceutical form: Tablet Route of administration: Orally




Primary Outcome Measures :
  1. Part B -To evaluate overall response rate (R) or complete response (CR) at Day 85 [ Time Frame: Through Day 85 ]

    R is defined as an increase in hemoglobin by ≥2 g/dL from baseline and an absence of transfusion in the last 7 days. Biochemical evidence of hemolysis may still be present.

    CR is defined as hemoglobin ≥11 g/dL (women) or ≥12 g/dL (men), no evidence of hemolysis (normal bilirubin, LDH, haptoglobin, and reticulocytes), and absence of transfusion from 6 weeks after the first isatuximab dose.



Secondary Outcome Measures :
  1. Part A (Cohorts 2 and 3 Only) -To evaluate overall response rate (R) or complete response (CR) at Day 85 [ Time Frame: Through Day 85 ]

    R is defined as an increase in hemoglobin by ≥2 g/dL from baseline and an absence of transfusion in the last 7 days. Biochemical evidence of hemolysis may still be present.

    CR is defined as hemoglobin ≥11 g/dL (women) or ≥12 g/dL (men), no evidence of hemolysis (normal bilirubin, LDH, haptoglobin, and reticulocytes), and absence of transfusion from 6 weeks after the first isatuximab dose.


  2. Part A (Cohorts 2 and 3 Only) -Overall response rate at Day 169, time to R or CR, time to loss of R or CR, proportion of participants requiring rescue therapy (any wAIHA-directed therapy other than prednisone or transfusion) or splenectomy [ Time Frame: Through Day 169 ]
    Overall response rate at Day 169, time to R or CR, time to loss of R or CR (loss of R defined as hemoglobin <10 g/dL at two consecutive visits at least 7 days apart and initiation of new treatment for anemia or increase in steroid dose; loss of CR is defined as hemoglobin <11 g/dL (women) or <12 g/dL (men) at two consecutive visits at least 7 days apart), proportion of participants requiring rescue therapy (any wAIHA-directed therapy other than prednisone or transfusion) or splenectomy.

  3. Part A (Cohorts 2 and 3 Only) -FACIT-fatigue scale score [ Time Frame: Through Day 169 ]
    -FACIT-fatigue scale score

  4. Part B -Overall response rate at Day 169, time to PR or CR, time to loss of PR or CR, proportion of participants requiring rescue therapy (any wAIHA-directed therapy other than prednisone or transfusion) or splenectomy [ Time Frame: Through Day 169 ]
    Overall response rate at Day 169, time to R or CR, time to loss of R or CR (loss of R defined as hemoglobin <10 g/dL at two consecutive visits at least 7 days apart and initiation of new treatment for anemia or increase in steroid dose; loss of CR is defined as hemoglobin <11 g/dL (women) or <12 g/dL (men) at two consecutive visits at least 7 days apart), proportion of participants requiring rescue therapy (any wAIHA-directed therapy other than prednisone or transfusion) or splenectomy.

  5. Part B -FACIT-fatigue scale score [ Time Frame: Through Day 169 ]
  6. Part A (All Cohorts) and B -Change from baseline in LDH [ Time Frame: Through Day 169 ]
  7. Part A (All Cohorts) and B -Change from baseline in haptoglobin [ Time Frame: Through Day 169 ]
  8. Part A (All Cohorts) and B -Change from baseline in reticulocytes [ Time Frame: Through Day 169 ]
  9. Part A (All Cohorts) and B -Change from baseline in total bilirubin [ Time Frame: Through Day 169 ]
  10. Part A (All Cohorts) and B -PK parameters after subcutaneous administrations [ Time Frame: Through Day 169 ]
    Maximum concentration received after injection (Cmax)

  11. Part A (All Cohorts) and B -PK parameters after subcutaneous administrations [ Time Frame: Through Day 169 ]
    Area under the plasma concentration versus time curve calculated over the dosing interval T (336 h) (AUC0-2week)

  12. Part A (All Cohorts) and B Incidence of anti-isatuximab antibodies [ Time Frame: Through Day 169 ]
  13. Part A (All Cohorts) and B Titer (if relevant) of anti-isatuximab antibodies [ Time Frame: Through Day 169 ]


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 :

  • Participant must be ≥18 to years of age, inclusive, at the time of signing the informed consent.

    - Males and females with a confirmed diagnosis of primary w AIHA or systemic lupus erythematosus (SLE)-associated w AIHA (without other SLE-related manifestations apart from cutaneous and musculoskeletal manifestations) who meet the following criteria:

    1. Hemoglobin level <10 g/dL at screening.
    2. Hemolysis (haptoglobin ≤4 mg/dL and total bilirubin above the upper limit of normal).
    3. Positive direct antiglobulin test (DAT) (IgG or IgG + complement C3d pattern or IgM warm autoantibodies (positive dual DAT)).

      • Participants who have previously failed to maintain a sustained response after treatment with corticosteroids (corticosteroid-refractory or corticosteroid-dependent primary wAIHA).
      • Part A only: Participants who have previously failed to maintain a sustained response after treatment with rituximab (or other anti-CD20 monoclonal antibodies). The last dose of the anti-CD20 antibody must have been administered at least 12 weeks before enrollment.
      • Part B: Participants who have had an insufficient response to at least 1 prior therapy in addition to corticosteroids (splenectomy is regarded as a prior therapy).
      • Contraceptive use by men and women

      Exclusion criteria:

  • 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 or her participation in the study as determined by the Investigator.

    • Serious infection that required hospitalization within 3 months prior to enrollment.
    • Secondary wAIHA from any cause including drugs, lymphoproliferative disorders, infectious or autoimmune disease (SLE without other SLE-related manifestations apart from cutaneous and musculoskeletal manifestations is allowed), or active hematologic malignancies. Participants with positive antinuclear antibodies but without a definitive diagnosis of an autoimmune disease are allowed.
    • History of coagulation or bleeding disorders (Evans Syndrome is allowed).
    • Uncontrolled or active HBV or HCV infection
    • HIV infection.
    • Serum gammaglobulin levels <3 g/L.
    • Females who are pregnant, lactating, or considered unreliable with respect to contraceptive practice.
    • Concurrent treatment with corticosteroids, unless the participant has been on a stable daily dose for ≥ 30 days prior to enrollment.
    • Treatment with cyclophosphamide within 4 weeks prior to enrollment.
    • Treatment with cytotoxic drugs (other than cyclophosphamide) within 12 weeks prior to enrollment.

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


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): NCT04661033


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

Locations
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United States, California
Investigational Site Number 8400001 Recruiting
Los Angeles, California, United States, 90033
Belgium
Investigational Site Number 0560001 Recruiting
Leuven, Belgium, 3000
Germany
Investigational Site Number 2760001 Recruiting
Essen, Germany, 45147
Hungary
Investigational Site Number 3480001 Recruiting
Budapest, Hungary, 1083
Netherlands
Investigational Site Number 5280001 Recruiting
Leiden, Netherlands, 2333 ZA
United Kingdom
Investigational Site Number 8260001 Recruiting
London, United Kingdom, NW1 2PG
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04661033    
Other Study ID Numbers: ACT16832
2020-003880-24 ( EudraCT Number )
U1111-1255-5350 ( Other Identifier: UTN )
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: October 4, 2021
Last Verified: October 2021
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:
(wAIHA)
Additional relevant MeSH terms:
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Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Hemolysis
Hematologic Diseases
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Acetaminophen
Diphenhydramine
Promethazine
Famotidine
Montelukast
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics
Anti-Asthmatic Agents
Respiratory System Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Sleep Aids, Pharmaceutical
Hypnotics and Sedatives
Central Nervous System Depressants