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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 : October 16, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: Crizanlizumab (SEG101) Drug: Placebo Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind Study
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : July 26, 2019
Estimated Primary Completion Date : May 30, 2022
Estimated Study Completion Date : November 5, 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Crizanlizumab (SEG101) at 5.0 mg/kg
Participants will receive Crizanlizumab (SEG101) at 5.0 mg/kg
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

Experimental: Crizanlizumab (SEG101) at 7.5 mg/kg
Participants will receive Crizanlizumab (SEG101) at 7.5 mg/kg
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

Placebo Comparator: Placebo
Participants will receive the placebo drug.
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Evolution of albuminuria and albumin creatinine ratio (ACR) [ Time Frame: 1 year ]
    To assess (sickle cell disease) SCD-related renal damage in each group.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Absolute change from baseline in hemoglobin [ Time Frame: 5 years ]
    To assess safety of crizanlizumab over the study period.

  14. Growth and sexual maturity assessment in [ Time Frame: 5 years ]
    To assess safety of crizanlizumab over the study period.

  15. Measurement of anti-drug antibodies (ADA) to crizanlizumab [ Time Frame: 5 years ]
    To assess immunogenicity of crizanlizumab over the study period.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 and older
  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 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. 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 As well as other complicated crises, such as acute chest syndrome, priapism, and hepatic or splenic sequestration
  5. If receiving HU/HC or erythropoietin stimulating agent or L-glutamine, must have been receiving the drug for at least 6 months prior to Screening visit and plan to continue taking at the same dose and schedule until the subject has reached one year of study treatment
  6. Patients must meet the following central laboratory values at the screening visit:

    • 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:

    • Resting QTcF ≥470 msec at pretreatment (baseline) for both male and female or inestability to determine QTc
    • 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 intructions and requirements.

Other protocol-defined Inclusion/Exclusion may apply.


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): NCT03814746


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Georgia
Childrens Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30342
Contact: Jon Sims    407-785-2025    Jonathan.sims@choa.org   
Principal Investigator: Robert Clark Brown         
United States, Pennsylvania
Thomas Jefferson University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Arrikka Mullins       Arrikka.mullins@jefferson.edu   
Principal Investigator: Sanaa Rizk         
United States, Texas
Cook Childrens Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Contact: Lynn Davisson       Lynn.Davisson@cookchildrens.org   
Principal Investigator: Clarissa Johnson         
Belgium
Novartis Investigative Site Recruiting
Edegem, Antwerpen, Belgium, 2650
Novartis Investigative Site Recruiting
Brussel, Belgium, 1000
Novartis Investigative Site Recruiting
Bruxelles, Belgium, 1070
Novartis Investigative Site Recruiting
Laeken, Belgium, 1020
France
Novartis Investigative Site Recruiting
Creteil, France, 94000
Novartis Investigative Site Recruiting
Marseille cedex 05, France, 13385
Novartis Investigative Site Recruiting
Paris, France, 75015
Germany
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Greece
Novartis Investigative Site Recruiting
Athens, Greece, 115 27
Italy
Novartis Investigative Site Recruiting
Verona, VR, Italy, 37126
Lebanon
Novartis Investigative Site Recruiting
Tripoli, Lebanon, 1434
Netherlands
Novartis Investigative Site Recruiting
Den Haag, Netherlands, 2545 CH
United Kingdom
Novartis Investigative Site Recruiting
Sheffield, South Yorkshire, United Kingdom, S10 2JF
Novartis Investigative Site Recruiting
London, United Kingdom, SE1 9RT
Novartis Investigative Site Recruiting
Sheffield, United Kingdom, S10 2TH
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03814746     History of Changes
Other Study ID Numbers: CSEG101A2301
2017-001746-10 ( EudraCT Number )
First Posted: January 24, 2019    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
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


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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 Novartis ( Novartis Pharmaceuticals ):
Sickle Cell Disease
red blood cells
sickle-like shape
sickle-cell trait
sickle-cell crisis
SEG101
Crizanlizumab
Hydroxyurea/ Hydroxycarbamide Therapy
Vaso-Occlusive Crises
SCA
blood disorders
hemoglobin
mutation in hemoglobin gene
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors