November, 11 2019

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)

Locations

3 United States sites, 4 Belgium sites, 2 Brazil sites, 3 France sites, 3 Germany sites, 1 Greece site, 1 Italy site, 1 Lebanon site, 1 Netherlands site, 1 Spain site, 4 United Kingdom sites

Age

> 12 Years

Phase

Phase 3

About the study

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 Type

Interventional

Phase

Phase 3

Age

> 12 Years

Gender

All

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.

Interventions

  • Drug

Outcome measures

  • Rate of vaso-occlusive crisis (VOC) events leading to healthcare visit

Location

  • Childrens Healthcare of Atlanta, Atlanta, Georgia, United States, 30342 [Recruiting]
  • Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States, 19107 [Recruiting]
  • Cook Childrens Medical Center, Fort Worth, Texas, United States, 76104 [Recruiting]
  • Novartis Investigative Site, Edegem, Antwerpen, Belgium, 2650 [Recruiting]
  • Novartis Investigative Site, Brussel, Belgium, 1000 [Recruiting]
  • Novartis Investigative Site, Bruxelles, Belgium, 1070 [Recruiting]
  • Novartis Investigative Site, Laeken, Belgium, 1020 [Recruiting]
  • Novartis Investigative Site, Ribeirao Preto, SP, Brazil, 14048-900 [Recruiting]
  • Novartis Investigative Site, Porto Alegre, Brazil, 90035-003 [Recruiting]
  • Novartis Investigative Site, Creteil, France, 94000 [Recruiting]
  • Novartis Investigative Site, Marseille cedex 05, France, 13385 [Recruiting]
  • Novartis Investigative Site, Paris, France, 75015 [Recruiting]
  • Novartis Investigative Site, Berlin, Germany, 13353 [Recruiting]
  • Novartis Investigative Site, Essen, Germany, 45147 [Recruiting]
  • Novartis Investigative Site, Stuttgart, Germany, 70376 [Recruiting]
  • Novartis Investigative Site, Athens, Greece, 115 27 [Recruiting]
  • Novartis Investigative Site, Verona, VR, Italy, 37126 [Recruiting]
  • Novartis Investigative Site, Tripoli, Lebanon, 1434 [Recruiting]
  • Novartis Investigative Site, Den Haag, Netherlands, 2545 CH [Recruiting]
  • Novartis Investigative Site, Barcelona, Catalunya, Spain, 08035 [Recruiting]
  • Novartis Investigative Site, Sheffield, South Yorkshire, United Kingdom, S10 2JF [Recruiting]
  • Novartis Investigative Site, London, United Kingdom, E1 1BB [Recruiting]
  • Novartis Investigative Site, London, United Kingdom, SE1 9RT [Recruiting]
  • Novartis Investigative Site, Sheffield, United Kingdom, S10 2TH [Recruiting]

Contact Research Team

  • Novartis Pharmaceuticals
    +41613241111
  • Novartis Pharmaceuticals
    1-888-669-6682

More info

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