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

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ClinicalTrials.gov Identifier: NCT03814746
Recruitment Status : Recruiting
First Posted : January 24, 2019
Last Update Posted : August 3, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE January 21, 2019
First Posted Date  ICMJE January 24, 2019
Last Update Posted Date August 3, 2020
Actual Study Start Date  ICMJE March 17, 2019
Estimated Primary Completion Date May 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 19, 2019)
Rate of vaso-occlusive crisis (VOC) events leading to healthcare visit [ Time Frame: 1 year ]
To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo in addition to standard of care.
Original Primary Outcome Measures  ICMJE
 (submitted: January 21, 2019)
Rate of vaso-occlusive crisis (VOC) events leading to [ Time Frame: 1 year ]
To compare the efficacy of 5.0 mg/kg versus placebo and 7.5 mg/kg of crizanlizumab versus placebo in addition to standard of care.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2020)
  • Rate of all VOCs leading to healthcare visit and treated at home (Key Secondary) [ Time Frame: 1 year, 5 years ]
    To compare the efficacy of 7.5 mg/kg versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit), based on documentation by health care provider following contact with participant.
  • Duration of VOCs leading to healthcare visit [ Time Frame: 1 year ]
    To compare the efficacy of 5.0 mg/kg versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit)
  • Number of subjects free from VOCs leading to healthcare visit [ Time Frame: 1 year ]
    To assess the time to first and second VOC leading to healthcare visit in each group versus placebo
  • Percentage of subjects free from VOCs leading to healthcare visit [ Time Frame: 1 year ]
    To assess the time to first and second VOC leading to healthcare visit in each group versus placebo
  • Time to first and second VOC leading to healthcare visit [ Time Frame: 1 year ]
    This is calculated respectively as the time from date of randomization until the first and the second VOC leading to healthcare visit over the first year.
  • Rate of visits to clinic, Emergency room (ER) and hospitalizations, both overall and VOC-related [ Time Frame: 1 year ]
    Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC- related
  • Evolution of albuminuria and albumin creatinine ratio (ACR) [ Time Frame: 1 year ]
    To assess (sickle cell disease) SCD-related renal damage in each group.
  • Pharmacokinetic (PK) profile of crizanlizumab: AUC [ Time Frame: after the first and fifth dose ]
    To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using AUC
  • PK profile of crizanlizumab: Cmax [ Time Frame: after the first and fifth dose ]
    To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using Cmax
  • PK profile of crizanlizumab: Tmax [ Time Frame: after the first and fifth dose ]
    To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using Tmax
  • PK profile of crizanlizumab: half-life [ Time Frame: after the first and fifth dose ]
    To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using half-life
  • PD parameter (P-selectin inhibition) [ Time Frame: after the first and fifth dose ]
    To characterize the pharmacodynamic (PD) (P-selectin inhibition) of crizanlizumab at 5.0 and 7.5 mg/kg
  • Absolute change from baseline in hemoglobin [ Time Frame: 5 years ]
    To assess safety of crizanlizumab over the study period.
  • Growth and sexual maturity assessment in [ Time Frame: 5 years ]
    To assess safety of crizanlizumab over the study period.
  • Measurement of anti-drug antibodies (ADA) to crizanlizumab [ Time Frame: 5 years ]
    To assess immunogenicity of crizanlizumab over the study period.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 21, 2019)
  • Rate of all VOCs leading to healthcare visit and treated at home (Key Secondary) [ Time Frame: 1 year, 5 years ]
    To compare the efficacy of 7.5 mg/kg versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit), based on documentation by health care provider following contact with participant.
  • Number of days with VOC leading to healthcare visit [ Time Frame: 1 year ]
    To compare the efficacy of 5.0 mg/kg versus placebo on the annualized rate of all VOCs (managed at home + leading to healthcare visit)
  • Number of subjects free from VOCs leading to healthcare visit [ Time Frame: 1 year ]
    To assess the time to first and second VOC leading to healthcare visit in each group versus placebo
  • Percentage of subjects free from VOCs leading to healthcare visit [ Time Frame: 1 year ]
    To assess the time to first and second VOC leading to healthcare visit in each group versus placebo
  • Time to first and second VOC leading to healthcare visit [ Time Frame: 1 year ]
    This is calculated respectively as the time from date of randomization until the first and the second VOC leading to healthcare visit over the first year.
  • Rate of visits to clinic, Emergency room (ER) and hospitalizations, both overall and VOC-related [ Time Frame: 1 year ]
    Healthcare resource utilization (visits to clinic, Emergency room (ER) and hospitalizations) both overall and VOC- related
  • Evolution of albuminuria and albumin creatinine ratio (ACR) [ Time Frame: 1 year ]
    To assess (sickle cell disease) SCD-related renal damage in each group.
  • Pharmacokinetic (PK) profile of crizanlizumab: AUC [ Time Frame: after the first and fifth dose ]
    To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using AUC
  • PK profile of crizanlizumab: Cmax [ Time Frame: after the first and fifth dose ]
    To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using Cmax
  • PK profile of crizanlizumab: Tmax [ Time Frame: after the first and fifth dose ]
    To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using Tmax
  • PK profile of crizanlizumab: half-life [ Time Frame: after the first and fifth dose ]
    To characterize the PK profile of crizanlizumab at 5.0 and 7.5 mg/kg using half-life
  • PD parameter (P-selectin inhibition) [ Time Frame: after the first and fifth dose ]
    To characterize the pharmacodynamic (PD) (P-selectin inhibition) of crizanlizumab at 5.0 and 7.5 mg/kg
  • Absolute change from baseline in hemoglobin [ Time Frame: 5 years ]
    To assess safety of crizanlizumab over the study period.
  • Growth and sexual maturity assessment in [ Time Frame: 5 years ]
    To assess safety of crizanlizumab over the study period.
  • Measurement of anti-drug antibodies (ADA) to crizanlizumab [ Time Frame: 5 years ]
    To assess immunogenicity of crizanlizumab over the study period.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Two Doses of Crizanlizumab Versus Placebo in Adolescent and Adult Sickle Cell Disease Patients
Official Title  ICMJE 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blind Study
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease (SCD)
Intervention  ICMJE
  • Drug: Crizanlizumab (SEG101)
    Crizanlizumab will be 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 Name: SEG101
  • Drug: Placebo
    Placebo will be supplied in single use 10 mL glass vials at a concentration of 10 mg/mL. One vial contains 100 mg of placebo. This is a concentrate for solution for infusion IV.
Study Arms  ICMJE
  • Experimental: Crizanlizumab (SEG101) at 5.0 mg/kg
    Participants will receive Crizanlizumab (SEG101) at 5.0 mg/kg
    Intervention: Drug: Crizanlizumab (SEG101)
  • Experimental: Crizanlizumab (SEG101) at 7.5 mg/kg
    Participants will receive Crizanlizumab (SEG101) at 7.5 mg/kg
    Intervention: Drug: Crizanlizumab (SEG101)
  • Placebo Comparator: Placebo
    Participants will receive the placebo drug.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 21, 2019)
240
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 29, 2027
Estimated Primary Completion Date May 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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

Other protocol-defined Inclusion/Exclusion may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Belgium,   Brazil,   Canada,   Colombia,   Finland,   France,   Germany,   Greece,   India,   Italy,   Jordan,   Lebanon,   Netherlands,   South Africa,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03814746
Other Study ID Numbers  ICMJE CSEG101A2301
2017-001746-10 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP