Study of two doses of crizanlizumab versus placebo in adolescent and adult sickle cell disease patients

Phase 1

• Conditions: Sickle Cell Disease with vaso-occlusive crisis; MedDRA version: 21.0Level: PTClassification code 10040644Term: Sickle cell diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.1Level: LLTClassification code 10002077Term: Anaemia sickle cellSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-001746-10-NL
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-04-23
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 240

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
4a. 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:
a. Pain crisis defined as an acute onset of pain for
which there is no other medically determined
explanation other than vaso- occlusion -
b. a visit to a medical facility and/or healthcare
professional,
c. and receipt of oral/parenteral opioids or parenteral nonsteroidal anti-inflammatory drug (NSAID) analgesics
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 at the same dose and schedule until the participant has reached one year of study treatment
6. Patients must meet the following central laboratory values prior to
Week 1 Day 1. In case of re-sampling needed, local laboratory values are allowed. Refer to Section 8.4.1 for further details:
• 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
Are the trial subjects under 18? yes
Number of subjects for this age range: 49
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

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
intructions and requirements.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified