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

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)

Sponsors

Lead Sponsor: Novartis Pharmaceuticals

Source Novartis
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.

Overall Status Active, not recruiting
Start Date 2019-07-26
Completion Date 2026-12-14
Primary Completion Date 2022-08-31
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Rate of vaso-occlusive crisis (VOC) events leading to healthcare visit 1 year
Secondary Outcome
Measure Time Frame
Rate of all VOCs leading to healthcare visit and treated at home (Key Secondary) 1 year, 5 years
Duration of VOCs leading to healthcare visit 1 year
Number of subjects free from VOCs leading to healthcare visit 1 year
Percentage of subjects free from VOCs leading to healthcare visit 1 year
Time to first and second VOC leading to healthcare visit 1 year
Rate of visits to clinic, Emergency room (ER) and hospitalizations, both overall and VOC-related 1 year
Evolution of albuminuria and albumin creatinine ratio (ACR) 1 year
Pharmacokinetic (PK) profile of crizanlizumab: AUC after the first and fifth dose
PK profile of crizanlizumab: Cmax after the first and fifth dose
PK profile of crizanlizumab: Tmax after the first and fifth dose
PK profile of crizanlizumab: half-life after the first and fifth dose
PD parameter (P-selectin inhibition) after the first and fifth dose
Absolute change from baseline in hemoglobin 5 years
Growth and sexual maturity assessment in 5 years
Measurement of anti-drug antibodies (ADA) to crizanlizumab 5 years
Enrollment 254
Condition
Intervention

Intervention Type: Drug

Intervention Name: Crizanlizumab (SEG101)

Description: 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

Intervention Type: Drug

Intervention Name: Placebo

Description: 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.

Arm Group Label: Placebo

Eligibility

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 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.

Gender:

All

Minimum Age:

12 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals
Overall Contact Contact information is only displayed when the study is recruiting subjects.
Location
Facility:
Novartis Investigative Site | Atlanta, Georgia, 30342, United States
Novartis Investigative Site | Boston, Massachusetts, 02118, United States
Novartis Investigative Site | Charlotte, North Carolina, 28204, United States
Novartis Investigative Site | Memphis, Tennessee, 38163, United States
Novartis Investigative Site | Houston, Texas, 77030, United States
Novartis Investigative Site | Edegem, Antwerpen, 2650, Belgium
Novartis Investigative Site | Brussel, 1000, Belgium
Novartis Investigative Site | Bruxelles, 1070, Belgium
Novartis Investigative Site | Salvador, Bahia, 41253-190, Brazil
Novartis Investigative Site | Belem, PA, 66033 000, Brazil
Novartis Investigative Site | Recife, Pernambuco, 50070-170, Brazil
Novartis Investigative Site | Rio de Janeiro, RJ, 20.211-030, Brazil
Novartis Investigative Site | Ribeirao Preto, SP, 14048-900, Brazil
Novartis Investigative Site | Sao Paulo, SP, 05403 000, Brazil
Novartis Investigative Site | Sao Paulo, SP, 08270-070, Brazil
Novartis Investigative Site | São Paulo, SP, 01232-010, Brazil
Novartis Investigative Site | Porto Alegre, 90035-003, Brazil
Novartis Investigative Site | Toronto, Ontario, M5G 2C4, Canada
Novartis Investigative Site | Montreal, Quebec, H2X 1R9, Canada
Novartis Investigative Site | Valledupar, Cesar, 5602310, Colombia
Novartis Investigative Site | Barranquilla, Colombia
Novartis Investigative Site | Monteria, Colombia
Novartis Investigative Site | Helsinki, FIN 00290, Finland
Novartis Investigative Site | Creteil, 94000, France
Novartis Investigative Site | Marseille Cedex 05, 13885, France
Novartis Investigative Site | Paris, 75015, France
Novartis Investigative Site | Berlin, 13353, Germany
Novartis Investigative Site | Essen, 45147, Germany
Novartis Investigative Site | Koeln, 50937, Germany
Novartis Investigative Site | Stuttgart, 70376, Germany
Novartis Investigative Site | Accra, Ghana
Novartis Investigative Site | Athens, 115 27, Greece
Novartis Investigative Site | Patras, 265 00, Greece
Novartis Investigative Site | Thessaloniki, GR 54636, Greece
Novartis Investigative Site | Bhubaneswar, Odisha, 751003, India
Novartis Investigative Site | Hyderabad, Telangana, 500082, India
Novartis Investigative Site | Genova, GE, 16128, Italy
Novartis Investigative Site | Milano, MI, 20122, Italy
Novartis Investigative Site | Verona, VR, 37126, Italy
Novartis Investigative Site | Napoli, 80138, Italy
Novartis Investigative Site | Irbid, 22110, Jordan
Novartis Investigative Site | Beirut, 1107 2020, Lebanon
Novartis Investigative Site | Tripoli, 1434, Lebanon
Novartis Investigative Site | Rotterdam, Zuid Holland, 3015 GD, Netherlands
Novartis Investigative Site | Amsterdam, 1105 AZ, Netherlands
Novartis Investigative Site | Den Haag, 2545 CH, Netherlands
Novartis Investigative Site | Muscat, 123, Oman
Novartis Investigative Site | Panama City, Republica De Panama, 0801, Panama
Novartis Investigative Site | Panama City, 0801, Panama
Novartis Investigative Site | Soweto, Gauteng, 2013, South Africa
Novartis Investigative Site | Barcelona, Catalunya, 08035, Spain
Novartis Investigative Site | Madrid, 28034, Spain
Novartis Investigative Site | Madrid, 28046, Spain
Novartis Investigative Site | Adana, 01330, Turkey
Novartis Investigative Site | Antakya / Hatay, 31100, Turkey
Novartis Investigative Site | Sheffield, South Yorkshire, S10 2JF, United Kingdom
Novartis Investigative Site | Cambridge, CB2 0QQ, United Kingdom
Novartis Investigative Site | London, SE1 9RT, United Kingdom
Novartis Investigative Site | London, SE5 9RS, United Kingdom
Novartis Investigative Site | Sheffield, S10 2TH, United Kingdom
Location Countries

Belgium

Brazil

Canada

Colombia

Finland

France

Germany

Ghana

Greece

India

Italy

Jordan

Lebanon

Netherlands

Oman

Panama

South Africa

Spain

Turkey

United Kingdom

United States

Verification Date

2022-11-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access Yes
Condition Browse
Number Of Arms 3
Arm Group

Label: Crizanlizumab (SEG101) at 5.0 mg/kg

Type: Experimental

Description: Participants will receive Crizanlizumab (SEG101) at 5.0 mg/kg

Label: Crizanlizumab (SEG101) at 7.5 mg/kg

Type: Experimental

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

Label: Placebo

Type: Placebo Comparator

Description: Participants will receive the placebo drug.

Acronym STAND
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Double-blind Study

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