Study of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients (STAND)

May 1, 2024 updated by: Novartis Pharmaceuticals

A Phase III, Multicenter, Randomized, Double-blind Study to Assess Efficacy and Safety of Two Doses of Crizanlizumab Versus Placebo, With or Without Hydroxyurea/ Hydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients With Vaso-Occlusive Crises (STAND)

The purpose of this study is to compare the efficacy and safety of 2 doses of crizanlizumab (5.0 mg/kg and 7.5 mg/kg) versus placebo in adolescent and adult sickle cell disease (SCD) patients with history of vaso-occlusive crisis (VOC) leading to healthcare visit.

Study Overview

Status

Active, not recruiting

Detailed Description

Study CSEG101A2301 (STAND) is an ongoing Phase III, multicenter, randomized, double-blind study to assess efficacy and safety of two doses of crizanlizumab (5 mg/kg and 7.5 mg/kg) versus placebo, with or without hydroxyurea/ hydroxycarbamide therapy (HU/HC), in adolescent and adult patients with SCD and history of VOC leading to healthcare visit.

This is a multicenter clinical trial comparing 2 doses of crizanlizumab (5 mg/kg and 7.5 mg/kg) versus placebo in addition to standard of care participants might be taking at the time of study start, in adolescent and adult participants with confirmed diagnosis of sickle cell disease (SCD) and history of vaso-occlusive crisis (VOC) leading to a healthcare visit.

240 participants (including 48 adolescents) were planned to be randomized in a 1:1:1 ratio to either 5 mg/kg, 7.5 mg/kg of crizanlizumab or placebo. Randomized participants were stratified by concomitant HU/HC usage (yes/no) and baseline rate of VOCs leading to a healthcare visit in 12 months prior to screening visit (2-4 vs. ≥ 5 VOCs) at the time of enrollment. In November 2020, a capping of 90 adult participants per strata was implemented to ensure adequate opportunity for enrollment into each of the 4 strata.

Study Type

Interventional

Enrollment (Actual)

252

Phase

  • Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Brussel, Belgium, 1000
        • Novartis Investigative Site
      • Bruxelles, Belgium, 1070
        • Novartis Investigative Site
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • Novartis Investigative Site
      • Porto Alegre, Brazil, 90035-003
        • Novartis Investigative Site
    • Bahia
      • Salvador, Bahia, Brazil, 41253-190
        • Novartis Investigative Site
    • PA
      • Belem, PA, Brazil, 66033 000
        • Novartis Investigative Site
    • Pernambuco
      • Recife, Pernambuco, Brazil, 50070-170
        • Novartis Investigative Site
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20.211-030
        • Novartis Investigative Site
    • SP
      • Ribeirao Preto, SP, Brazil, 14048-900
        • Novartis Investigative Site
      • Sao Paulo, SP, Brazil, 05403 000
        • Novartis Investigative Site
      • Sao Paulo, SP, Brazil, 08270-070
        • Novartis Investigative Site
      • São Paulo, SP, Brazil, 01232-010
        • Novartis Investigative Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H2X 1R9
        • Novartis Investigative Site
      • Barranquilla, Colombia, 080020
        • Novartis Investigative Site
      • Monteria, Colombia, 230004
        • Novartis Investigative Site
    • Cesar
      • Valledupar, Cesar, Colombia, 5602310
        • Novartis Investigative Site
      • Helsinki, Finland, FIN 00290
        • Novartis Investigative Site
      • Creteil, France, 94010
        • Novartis Investigative Site
      • Marseille Cedex 05, France, 13885
        • Novartis Investigative Site
      • Paris, France, 75015
        • Novartis Investigative Site
      • Berlin, Germany, 13353
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Koeln, Germany, 50937
        • Novartis Investigative Site
      • Stuttgart, Germany, 70376
        • Novartis Investigative Site
      • Accra, Ghana, 0437-0594
        • Novartis Investigative Site
      • Athens, Greece, 115 27
        • Novartis Investigative Site
      • Patras, Greece, 265 00
        • Novartis Investigative Site
      • Thessaloniki, Greece, GR 54636
        • Novartis Investigative Site
    • Odisha
      • Bhubaneswar, Odisha, India, 751003
        • Novartis Investigative Site
    • Telangana
      • Hyderabad, Telangana, India, 500082
        • Novartis Investigative Site
      • Napoli, Italy, 80138
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italy, 16128
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20122
        • Novartis Investigative Site
    • VR
      • Verona, VR, Italy, 37126
        • Novartis Investigative Site
      • Irbid, Jordan, 22110
        • Novartis Investigative Site
      • Beirut, Lebanon, 1107 2020
        • Novartis Investigative Site
      • Tripoli, Lebanon, 1434
        • Novartis Investigative Site
      • Amsterdam, Netherlands, 1105 AZ
        • Novartis Investigative Site
      • Den Haag, Netherlands, 2545 CH
        • Novartis Investigative Site
    • Zuid Holland
      • Rotterdam, Zuid Holland, Netherlands, 3015 GD
        • Novartis Investigative Site
      • Muscat, Oman, 123
        • Novartis Investigative Site
      • Panama, Panama, 0801
        • Novartis Investigative Site
      • Panama City, Panama, 0801
        • Novartis Investigative Site
    • Republica De Panama
      • Panama City, Republica De Panama, Panama, 0801
        • Novartis Investigative Site
    • Gauteng
      • Soweto, Gauteng, South Africa, 2013
        • Novartis Investigative Site
      • Madrid, Spain, 28034
        • Novartis Investigative Site
      • Madrid, Spain, 28046
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Adana, Turkey, 01330
        • Novartis Investigative Site
      • Antakya / Hatay, Turkey, 31100
        • Novartis Investigative Site
      • Cambridge, United Kingdom, CB2 0QQ
        • Novartis Investigative Site
      • London, United Kingdom, SE1 9RT
        • Novartis Investigative Site
      • London, United Kingdom, SE5 9RS
        • Novartis Investigative Site
      • Sheffield, United Kingdom, S10 2TH
        • Novartis Investigative Site
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Novartis Investigative Site
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Childrens Healthcare of Atlanta .
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Insitute Carolinas Healthcare System
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • Univ of Tenn Health Sciences Ctr
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas Health Science Center at Houston

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. Written informed consent must be obtained prior to any screening procedures
  2. Male or female patients aged 12 years and older on the day of signing informed consent. Adolescent include patients aged 12 to 17 years old and adults ≥ 18 years
  3. Confirmed diagnosis of SCD by hemoglobin electrophoresis or high performance liquid chromatography (HPLC) [performed locally]. All SCD genotypes are eligible, genotyping is not required for study entry
  4. Experienced at least 2 VOCs leading to healthcare visit within the 12 months prior to screening visit as determined by medical history. Prior VOC leading to healthcare visit must resolve at least 7 days prior to Week 1 Day 1 and must include:

    1. Pain crisis defined as an acute onset of pain for which there is no other medically determined explanation other than vaso- occlusion -
    2. which requires a visit to a medical facility and/or healthcare professional,
    3. and receipt of oral/parenteral opioids or parenteral nonsteroidal anti-inflammatory drug (NSAID) analgesia Acute chest syndrome (ACS), priapism and hepatic or splenic sequestration will be considered VOC in this study
  5. If receiving HU/HC or L-glutamine (local HA approved medicinal product), must have been receiving the drug for at least 6 months and at a stable dose for at least 3 months prior to Screening visit and plan to continue taking it at the same dose and schedule until the subject has reached one year of study treatment. Patients who have not been receiving such drug must not have received it for at least 6 months prior to Screening visit to be included. Patients must have evidence of insufficient control of acute pain, such as at least one VOC leading to healthcare visit while on HU/HC or L-Glutamine treatment. If receiving erythropoietin stimulating agent, must have been receiving the drug for at least 6 months prior to Screening visit and plan to continue taking the treatment to maintain stable Hb levels at least until the subject has reached one year of study treatment
  6. Patients must meet the following central laboratory values prior to Week 1 Day 1:

    • Absolute Neutrophil Count ≥1.0 x 109/L
    • Platelet count ≥75 x 109/L
    • Hemoglobin: for adults (Hb) ≥4.0 g/dL and for adolescents (Hb) ≥5.5 g/dL
    • Glomerular filtration rate ≥ 45 mL/min/1.73 m2 using CKD-EPI formula in adults, and Shwartz formula in adolescents
    • Direct (conjugated) bilirubin < 2.0 x ULN
    • Alanine transaminase (ALT) < 3.0 x ULN
  7. ECOG performance status ≤2.0 for adults and Karnofsky ≥ 50% for adolescents

Key Exclusion Criteria:

  1. History of stem cell transplant.
  2. Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted.
  3. Contraindication or hypersensitivity to any drug or metabolites from similar class as study drug or to any excipients of the study drug formulation. History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.
  4. Received active treatment on another investigational trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to Screening visit or plans to participate in another investigational drug trial.
  5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception during dosing and for 15 weeks after stopping treatment.
  6. Concurrent severe and/or uncontrolled medical conditions which, in the opinion of the Investigator, could cause unacceptable safety risks or compromise participation in the study.
  7. History or current diagnosis of ECG abnormalities indicating significant risk of safety such as:

    • Concomitant clinically significant cardiac arrhythmias (e.g ventricular tachycardia), and clinically significant second or third degree AV block without a pacemaker
    • History of familial long QT syndrome or know family history of Torsades de Pointes
  8. Not able to understand and to comply with study instructions and requirements.
  9. Received prior treatment with crizanlizumab or other selectin targeting agent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Crizanlizumab (SEG101) at 5.0 mg/kg
Participants received Crizanlizumab (SEG101) at 5.0 mg/kg

Crizanlizumab was supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. This is a concentrate for solution for infusion.

IV.

Other Names:
  • SEG101
Experimental: Crizanlizumab (SEG101) at 7.5 mg/kg
Participants received Crizanlizumab (SEG101) at 7.5 mg/kg

Crizanlizumab was supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. This is a concentrate for solution for infusion.

IV.

Other Names:
  • SEG101
Placebo Comparator: Placebo
Participants received the placebo drug.
Placebo was supplied in single use 10 mL glass vials at a concentration of 0 mg/mL. This is a concentrate for solution for infusion IV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to a Healthcare Visit
Time Frame: 1 year

VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration.

Healthcare visit is defined as any visit to a medical facility such as emergency room (ER), hospital and/or office visit, which includes pain management of VOC in situ.

Annualized rate of corresponding VOC events = (Number of corresponding VOC events * 365)/(number of days in the observation period).

Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).

1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over the First-year Post Randomization (Key Secondary)
Time Frame: 1 year
VOCs are based on documentation by provider following contact with participant. VOC:pain crisis requiring therapy with oral/parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome, priapism and hepatic or splenic sequestration. Healthcare visit:a visit to a medical facility (ER, hospital &/or office visit resulting in pain management of VOC. Managed at home: no visit to any medical facility &/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice is allowed. Annualized rate of corresponding VOC events = (# of corresponding VOC events * 365)/(# of days in observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor & erythropoietin therapies to treat SCD &/or to prevent/reduce VOCs), date of randomization + 365 days)
1 year
Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over 5 Years Post Randomization (Key Secondary)
Time Frame: 5 years
To compare the efficacy of 5.0 mg/kg vs placebo & 7.5 mg/kg vs placebo on the annualized rate of all VOCs based on documentation by provider following contact with participant. VOC is defined as pain crisis (an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) requiring therapy with oral/parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome, priapism and hepatic or splenic sequestration. Healthcare visit is defined as a visit to a medical facility (emergency room, hospital and/or office visit resulting in pain management of VOC. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice is allowed. The annualized rate of VOC leading to healthcare visit is the number of VOC leading to healthcare visit multiplied by 365 & divided by the number of days in observation period.
5 years
Mean Duration of VOCs Leading to a Healthcare Visit Over the First-year Post Randomization
Time Frame: 1 year
To assess the duration of VOCs leading to healthcare visit in each group. Mean duration of VOC per participant is defined as the average duration of all individual episodes of VOCs leading to healthcare visits of a given participant (a VOC duration is defined as end date of the VOC - start date of the VOC + 1). Participants with no VOC leading to healthcare visits have been excluded.
1 year
Number of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization
Time Frame: 1 year

To assess the number of participants free from VOCs leading to healthcare visit.

VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. A participant is free from VOC if they do not have a VOC crisis.

1 year
Percentage of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization
Time Frame: 1 year
To assess the percentage of participants free from VOCs leading to healthcare visit. VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. A participant is free from VOC if they do not have a VOC crisis.
1 year
Time to First and Second VOCs Leading to a Healthcare Visit Over the First-year Post Randomization
Time Frame: 1 year

To assess the time to first and second VOC leading to healthcare visit in each group.

Time to first occurrence of VOC leading to a healthcare visit is defined as the time from the date of randomization to the date of the first occurrence of the VOC.

Time to second occurrence of VOC leading to a healthcare visit is defined as the time from date of randomization to the date of the second occurrence of VOC.

1 year
Annualized Rate of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization
Time Frame: 1 year

To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC-related in each group.

Annualized rate of corresponding healthcare visits =(Number of corresponding healthcare visits * 365)/(number of days in the observation period).

Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days)

1 year
Annualized Days of Visits to Clinic, Emergency Room (ER) and Hospitalizations, Both Overall and VOC-related Over the First-year Post-randomization
Time Frame: 1 year

To assess Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC-related in each group.

Annualized days of corresponding healthcare visits =(Number of days =(Number of days of corresponding healthcare visits * 365)/(number of days in the observation period).

Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).

1 year
Evolution of Albumin Creatinine Ratio (ACR) Over the First-year Post-randomization (Change From Baseline)
Time Frame: Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1)
Laboratory values for parameters related to renal function (creatinine, estimated glomerular filtration rate, urine microalbumin, and urine albumin/creatinine ratio) were measured at 6-month intervals over time from baseline.
Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1)
Evolution of Albuminuria (Urine Microalbumin) Over the First-year Post-randomization (Change From Baseline)
Time Frame: Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1)
Laboratory values for parameters related to renal function (creatinine, estimated glomerular filtration rate, urine microalbumin, and urine albumin/creatinine ratio) were measured at 6-month intervals over time from baseline.
Over first year post-randomization (Baseline, Week 27 Day 1, Week 51 Day 1)
Pharmacokinetic (PK) Profile of Crizanlizumab: AUCd15, AUCtau
Time Frame: AUCd15 (first-dose) was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) to W3D1; AUCtau (steady-state) was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1
To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Area under the (concentration-time profile) curve.
AUCd15 (first-dose) was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) to W3D1; AUCtau (steady-state) was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1
PK Profile of Crizanlizumab: Cmax
Time Frame: first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1
To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Maximum concentration.
first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1
PK Profile of Crizanlizumab: Tmax
Time Frame: first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1
To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: Time to maximum concentration.
first-dose was assessed at W1D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose) through to W3D1; steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1
PK Profile of Crizanlizumab: Half-life
Time Frame: steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1
To characterize the pharmacokinetic (PK) profile of crizanlizumab at 5.0 and 7.5 mg/kg: half life.
steady-state was assessed at W15D1 (pre-dose, 0.5 hr, 2 hrs and 4 hrs post-dose), W15D2, W15D4, W16D1, W17D1, W18D1, W19D1
PD Parameter (P-selectin Inhibition)
Time Frame: AUCd15 (first dose): W1D1, W1D2, W1D4, W2D1 and W3D1; steady state: W15D1, W15D2, W15D4, W16D1, W17D1 W18D1 and W19D1
To characterize the pharmacodynamic (PD) of crizanlizumab at 5.0 and 7.5 mg/kg: P-selectin inhibition (% inhibition multipled by hr)
AUCd15 (first dose): W1D1, W1D2, W1D4, W2D1 and W3D1; steady state: W15D1, W15D2, W15D4, W16D1, W17D1 W18D1 and W19D1
Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 1 Year
Time Frame: 1 year

To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit. VOC is defined as pain crisis which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit: any visit to a medical facility such as ER, hospital and/or office visit, which includes pain management of VOC in situ.

Annualized rate of corresponding VOC events = (Number of corresponding VOC events * 365)/(number of days in the observation period).

Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).

1 year
Annualized Rate of Various Subtypes of VOCs Leading to a Healthcare Visit at 5 Years
Time Frame: 5 years

To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the annualized rate of VOCs leading to healthcare visit.

VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration.

Healthcare visit is defined as any visit to a medical facility such as emergency room, hospital and/or office visit, which includes pain management of VOC in situ.

The annualized rate of VOC leading to healthcare visit is the number of VOC leading to healthcare visit multiplied by 365 and divided by the number of days in the observation period.

5 years
Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home at 5 Years
Time Frame: 5 years
To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the rates of all VOCs (managed at home + leading to healthcare visit).
5 years
Number of VOCs Managed at Home at Year 1
Time Frame: 1 year

To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the number of VOC events that were managed at home.

VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice was allowed.

1 year
Number of VOCs Managed at Home at 5 Years
Time Frame: 5 years

To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo on the number of VOC events that were managed at home.

VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Managed at home is defined as no visit to any medical facility and/or healthcare professional to receive treatment for VOC. Healthcare contact for medical advice was allowed.

5 years
Absolute Change From Baseline in Hemoglobin
Time Frame: 5 years
To assess safety of crizanlizumab over the study period.
5 years
Growth and Sexual Maturity Assessment in Adolescents (Tanner Stage)
Time Frame: 5 years
To assess safety of crizanlizumab over the study period.
5 years
Immunogenicity: Measurement of Anti-drug Antibodies (ADA) to Crizanlizumab
Time Frame: 5 years
To assess immunogenicity of crizanlizumab over the study period.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2019

Primary Completion (Actual)

August 31, 2022

Study Completion (Estimated)

December 14, 2026

Study Registration Dates

First Submitted

January 21, 2019

First Submitted That Met QC Criteria

January 21, 2019

First Posted (Actual)

January 24, 2019

Study Record Updates

Last Update Posted (Actual)

May 3, 2024

Last Update Submitted That Met QC Criteria

May 1, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sickle Cell Disease (SCD)

Clinical Trials on Crizanlizumab (SEG101)

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