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

NCT03814746 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: CSEG101A23012017-001746-10
• Study Type: interventional
• Target: 255
• Locations: 21 countries
• Sites: 59

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.

Conditions

Sickle Cell Disease (SCD)

Keywords

Sickle Cell Disease; SCD; SEG101; Crizanlizumab; Hydroxyurea/ Hydroxycarbamide Therapy; Vaso-Occlusive Crises; SCA; blood disorders; hemoglobin; red blood cells; sickle-like shape; mutation in hemoglobin gene; sickle-cell trait; sickle-cell crisis

Outcome Measures

Primary Outcomes (1)

• Annualized Rate of Vaso-occlusive Crisis (VOC) Events Leading to a Healthcare Visit

  VOC is defined as pain crisis (defined as an acute onset of pain for which there is no other medically determined explanation other than vaso-occlusion) which requires therapy with oral or parenteral opioids or parenteral NSAID as well as other complicated crisis such as acute chest syndrome (ACS), priapism and hepatic or splenic sequestration. Healthcare visit is defined as any visit to a medical facility such as emergency room (ER), hospital and/or office visit, which includes pain management of VOC in situ. Annualized rate of corresponding VOC events = (Number of corresponding VOC events \* 365)/(number of days in the observation period). Observation period = time from date of randomization to minimum of (last dose date until treatment discontinuation + 27 days, date of initiation or discontinuation of HU/HC or L-Glutamine (or other therapies such as Voxelotor and erythropoietin therapies to treat SCD and/or to prevent/reduce VOCs), date of randomization + 365 days).

  1 year

Secondary Outcomes (23)

• Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over the First-year Post Randomization (Key Secondary)

  1 year

• Annualized Rate of All VOCs Leading to a Healthcare Visit and Treated at Home Over 5 Years Post Randomization (Key Secondary)

  5 years

• Mean Duration of VOCs Leading to a Healthcare Visit Over the First-year Post Randomization

  1 year

• Number of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization

  1 year

• Percentage of Participants Free From VOCs Leading to a Healthcare Visit Over the First-year Post Randomization

  1 year

Study Arms (3)

Crizanlizumab (SEG101) at 5.0 mg/kg

EXPERIMENTAL

Participants received Crizanlizumab (SEG101) at 5.0 mg/kg

Drug: Crizanlizumab (SEG101)

Crizanlizumab (SEG101) at 7.5 mg/kg

EXPERIMENTAL

Participants received Crizanlizumab (SEG101) at 7.5 mg/kg

Drug: Crizanlizumab (SEG101)

Placebo

PLACEBO COMPARATOR

Participants received the placebo drug.

Drug: Placebo

Interventions

Crizanlizumab (SEG101) DRUG

Crizanlizumab was 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.

Also known as: SEG101

Crizanlizumab (SEG101) at 5.0 mg/kg; Crizanlizumab (SEG101) at 7.5 mg/kg

Placebo DRUG

Placebo was supplied in single use 10 mL glass vials at a concentration of 0 mg/mL. This is a concentrate for solution for infusion IV.

Placebo

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent must be obtained prior to any screening procedures
• 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
• 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
• 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:
• Pain crisis defined as an acute onset of pain for which there is no other medically determined explanation other than vaso- occlusion -
• which requires a visit to a medical facility and/or healthcare professional,
• 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
• 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
• 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

You may not qualify if:

• History of stem cell transplant.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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
• Not able to understand and to comply with study instructions and requirements.
• Received prior treatment with crizanlizumab or other selectin targeting agent

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (59)

Childrens Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Levine Cancer Insitute Carolinas Healthcare System

Charlotte, North Carolina, 28204, United States

Location

Univ of Tenn Health Sciences Ctr

Memphis, Tennessee, 38163, United States

Location

U of TX Health Science Ct

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Brussels, Brussels Capital, 1070, Belgium

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Edegem, 2650, Belgium

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Novartis Investigative Site

Belém, Pará, 66033 000, Brazil

Location

Novartis Investigative Site

Recife, Pernambuco, 50070-170, Brazil

Location

Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20211-030, Brazil

Location

Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

Novartis Investigative Site

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 01232-010, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 08270-070, Brazil

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2C4, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2X 1R9, Canada

Location

Novartis Investigative Site

Barranquilla, Atlántico, 080020, Colombia

Location

Novartis Investigative Site

Valledupar, Cesar Department, 200001, Colombia

Location

Novartis Investigative Site

Montería, 230004, Colombia

Location

Novartis Investigative Site

Helsinki, FIN 00290, Finland

Location

Novartis Investigative Site

Créteil, 94010, France

Location

Novartis Investigative Site

Marseille, 13885, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Accra, GA-270-9830, Ghana

Location

Novartis Investigative Site

Athens, 115 27, Greece

Location

Novartis Investigative Site

Pátrai, 265 04, Greece

Location

Novartis Investigative Site

Thessaloniki, 54636, Greece

Location

Novartis Investigative Site

Bhubaneswar, Odisha, 751003, India

Location

Novartis Investigative Site

Hyderabad, Telangana, 500082, India

Location

Novartis Investigative Site

Genova, GE, 16128, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Verona, VR, 37134, Italy

Location

Novartis Investigative Site

Naples, 80138, Italy

Location

Novartis Investigative Site

Irbid, 22110, Jordan

Location

Novartis Investigative Site

Beirut, 113-0236, Lebanon

Location

Novartis Investigative Site

Tripoli, 1434, Lebanon

Location

Novartis Investigative Site

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Novartis Investigative Site

The Hague, South Holland, 2545 AA, Netherlands

Location

Novartis Investigative Site

Khoudh, 123, Oman

Location

Novartis Investigative Site

Panama City, Republica de Panama, 0801, Panama

Location

Novartis Investigative Site

Panama City, 0801, Panama

Location

Novartis Investigative Site

Soweto, Gauteng, 2013, South Africa

Location

Novartis Investigative Site

Barcelona, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Adana, Saricam, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Sheffield, South Yorkshire, S10 2JF, United Kingdom

Location

Novartis Investigative Site

Cambridge, CB2 0QQ, United Kingdom

Location

Novartis Investigative Site

London, SE1 9RT, United Kingdom

Location

Novartis Investigative Site

London, SE5 9RS, United Kingdom

Location

Novartis Investigative Site

Sheffield, S10 2TH, United Kingdom

Location

Related Publications (2)

• Abboud MR, Cancado RD, De Montalembert M, Smith WR, Rimawi H, Voskaridou E, Guvenc B, Ataga KI, Keefe D, Grosch K, Watson J, Reshetnyak E, Nassin ML, Dei-Adomakoh Y. Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial. Lancet Haematol. 2025 Apr;12(4):e248-e257. doi: 10.1016/S2352-3026(24)00384-3. Epub 2025 Mar 12.

  PMID: 40088922 DERIVED

• Obadina M, Wilson S, Derebail VK, Little J. Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations. Kidney360. 2023 Jul 1;4(7):997-1005. doi: 10.34067/KID.0000000000000162. Epub 2023 May 31.

  PMID: 37254256 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Vaso-Occlusive Crises; Hematologic Diseases; Sickle Cell Trait

Interventions

crizanlizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind Study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: January 24, 2019
• Study Start: July 26, 2019
• Primary Completion: August 31, 2022
• Study Completion (Estimated): November 23, 2026
• Last Updated: June 8, 2026
• Results First Posted: January 8, 2024

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

GR (3); OM (1); IT (4); JO (1); FI (1); ZA (1); FR (3); CO (3); US (5); LE (2); ES (3); BE (3); IN (2); GB (5); DE (4); GH (1); TU (1); CA (2); NL (3); BR (9); PA (2)