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)

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 point of contact

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

Locations

9 United States sites

9 Brazil sites

6 United Kingdom sites

5 Italy sites

5 Germany sites

5 Belgium sites

4 Spain sites

3 Netherlands sites

3 Colombia sites

3 Greece sites

3 France sites

3 India sites

2 Panama sites

2 Canada sites

2 Lebanon sites

2 Turkey sites

1 South Africa site

1 Kenya site

1 United Arab Emirates site

1 Finland site

1 Ghana site

1 Jordan site

1 Oman site

Age

> 12 Years

Phase

Phase 3

Study type

Interventional

Gender

All

Interventions

Drug

Compensation

Unknown

participation requirements

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

participation restrictions

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.

Locations

  • Valledupar, Cesar, Colombia, Novartis Investigative Site, 5602310 [Active, not recruiting]
  • Hollywood, Florida, United States, Memorial Cancer Institute Regulatory Contact, 33021 [Recruiting]
  • Atlanta, Georgia, United States, Childrens Healthcare of Atlanta, 30342 [Recruiting]
  • Boston, Massachusetts, United States, Boston Medical Center, 02118 [Recruiting]
  • Bronx, New York, United States, Jacobi Medical Center, 10461 [Recruiting]
  • Charlotte, North Carolina, United States, Levine Cancer Insitute Carolinas Healthcare System, 28204 [Recruiting]
  • Philadelphia, Pennsylvania, United States, Thomas Jefferson University Hospital, 19107 [Withdrawn]
  • Memphis, Tennessee, United States, Univ of Tenn Health Sciences Ctr, 38163 [Recruiting]
  • Fort Worth, Texas, United States, Cook Childrens Medical Center, 76104 [Withdrawn]
  • Houston, Texas, United States, University of Texas Health Science Center at Houston, 77030 [Recruiting]
  • Edegem, Antwerpen, Belgium, Novartis Investigative Site, 2650 [Recruiting]
  • Brussel, Belgium, Novartis Investigative Site, 1000 [Recruiting]
  • Bruxelles, Belgium, Novartis Investigative Site, 1070 [Recruiting]
  • Laeken, Belgium, Novartis Investigative Site, 1020 [Recruiting]
  • Liege, Belgium, Novartis Investigative Site, 4000 [Withdrawn]
  • Salvador, Bahia, Brazil, Novartis Investigative Site, 41253-190 [Active, not recruiting]
  • Belem, PA, Brazil, Novartis Investigative Site, 66033 000 [Active, not recruiting]
  • Recife, Pernambuco, Brazil, Novartis Investigative Site, 50070-170 [Active, not recruiting]
  • Rio de Janeiro, RJ, Brazil, Novartis Investigative Site, 20.211-030 [Active, not recruiting]
  • Ribeirao Preto, SP, Brazil, Novartis Investigative Site, 14048-900 [Active, not recruiting]
  • Sao Paulo, SP, Brazil, Novartis Investigative Site, 05403 000 [Active, not recruiting]
  • Sao Paulo, SP, Brazil, Novartis Investigative Site, 08270-070 [Active, not recruiting]
  • São Paulo, SP, Brazil, Novartis Investigative Site, 01232-010 [Active, not recruiting]
  • Porto Alegre, Brazil, Novartis Investigative Site, 90035-003 [Active, not recruiting]
  • Toronto, Ontario, Canada, Novartis Investigative Site, M5G 2C4 [Recruiting]
  • Montreal, Quebec, Canada, Novartis Investigative Site, H2X 1R9 [Recruiting]
  • Barranquilla, Colombia, Novartis Investigative Site [Active, not recruiting]
  • Monteria, Colombia, Novartis Investigative Site [Active, not recruiting]
  • Helsinki, Finland, Novartis Investigative Site, FIN 00290 [Active, not recruiting]
  • Creteil, France, Novartis Investigative Site, 94000 [Recruiting]
  • Marseille Cedex 05, France, Novartis Investigative Site, 13885 [Recruiting]
  • Paris, France, Novartis Investigative Site, 75015 [Recruiting]
  • Berlin, Germany, Novartis Investigative Site, 13353 [Recruiting]
  • Essen, Germany, Novartis Investigative Site, 45147 [Recruiting]
  • Hamburg, Germany, Novartis Investigative Site, 20246 [Withdrawn]
  • Koeln, Germany, Novartis Investigative Site, 50937 [Recruiting]
  • Stuttgart, Germany, Novartis Investigative Site, 70376 [Recruiting]
  • Accra, Ghana, Novartis Investigative Site [Recruiting]
  • Athens, Greece, Novartis Investigative Site, 115 27 [Active, not recruiting]
  • Patras, Greece, Novartis Investigative Site, 265 00 [Recruiting]
  • Thessaloniki, Greece, Novartis Investigative Site, GR 54636 [Active, not recruiting]
  • Bhubaneswar, Odisha, India, Novartis Investigative Site, 751003 [Recruiting]
  • Hyderabad, Telangana, India, Novartis Investigative Site, 500082 [Recruiting]
  • Vellore, India, Novartis Investigative Site [Recruiting]
  • Genova, GE, Italy, Novartis Investigative Site, 16128 [Active, not recruiting]
  • Milano, MI, Italy, Novartis Investigative Site, 20122 [Active, not recruiting]
  • Palermo, PA, Italy, Novartis Investigative Site, 90146 [Withdrawn]
  • Verona, VR, Italy, Novartis Investigative Site, 37126 [Active, not recruiting]
  • Napoli, Italy, Novartis Investigative Site, 80138 [Completed]
  • Irbid, Jordan, Novartis Investigative Site, 22110 [Active, not recruiting]
  • Eldoret, Kenya, Novartis Investigative Site, 8088-30100 [Recruiting]
  • Beirut, Lebanon, Novartis Investigative Site, 1107 2020 [Active, not recruiting]
  • Tripoli, Lebanon, Novartis Investigative Site, 1434 [Active, not recruiting]
  • Amsterdam, Netherlands, Novartis Investigative Site, 1105 AZ [Recruiting]
  • Den Haag, Netherlands, Novartis Investigative Site, 2545 CH [Recruiting]
  • Rotterdam, Netherlands, Novartis Investigative Site, 3015 GD [Recruiting]
  • Muscat, Oman, Novartis Investigative Site, 123 [Active, not recruiting]
  • Panama City, Republica De Panama, Panama, Novartis Investigative Site, 0801 [Recruiting]
  • Panama City, Panama, Novartis Investigative Site, 0801 [Recruiting]
  • Soweto, Gauteng, South Africa, Novartis Investigative Site, 2013 [Recruiting]
  • Salt, Cataluna, Spain, Novartis Investigative Site, 17190 [Withdrawn]
  • Barcelona, Catalunya, Spain, Novartis Investigative Site, 08035 [Recruiting]
  • Madrid, Spain, Novartis Investigative Site, 28034 [Recruiting]
  • Madrid, Spain, Novartis Investigative Site, 28046 [Recruiting]
  • Adana, Turkey, Novartis Investigative Site, 01330 [Recruiting]
  • Antakya / Hatay, Turkey, Novartis Investigative Site, 31100 [Recruiting]
  • Dubai, United Arab Emirates, Novartis Investigative Site, 9115 [Recruiting]
  • Sheffield, South Yorkshire, United Kingdom, Novartis Investigative Site, S10 2JF [Recruiting]
  • Cambridge, United Kingdom, Novartis Investigative Site, CB2 0QQ [Recruiting]
  • London, United Kingdom, Novartis Investigative Site, E1 1BB [Recruiting]
  • London, United Kingdom, Novartis Investigative Site, SE1 9RT [Recruiting]
  • London, United Kingdom, Novartis Investigative Site, SE5 9RS [Recruiting]
  • Sheffield, United Kingdom, Novartis Investigative Site, S10 2TH [Recruiting]
Last updated 2021-10-11