Phase 2, multicenter, open study aimed at evaluating the correct dose and safety of Crizanlizumab with or without Hydroxyurea/Hydroxycarbamide, in sequential age groups with decreasing age in pediatric sickle cell anemia patients who have had vaso-occlusive crises

Belgium, Brazil, Canada, Colombia, France, Germany, India, Italy, Lebanon, Oman, Spain, Switzerland, Turkey, United Kingdom, United States (ICTRP)

ID di studio ICTRP
EUCTR2017-001747-12 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
A phase 2, Multicenter, Open-Label Study to Assess Appropriate Dosing and to Evaluate Safety of Crizanlizumab, with or without Hydroxyurea/Hydroxycarbamide, in Sequential, Descending Age Groups of Pediatric Sickle Cell Disease Patients with Vaso-Occlusive Crisis. (BASEC)

Titolo accademico
A phase 2, Multicenter, Open-Label Study to Assess Appropriate Dosing and to Evaluate Safety ofCrizanlizumab, with or without Hydroxyurea/Hydroxycarbamide, in Sequential,Descending Age Groups of Pediatric Sickle Cell Disease Patients with Vaso-Occlusive Crisis (ICTRP)

Titolo pubblico
Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients (ICTRP)

Malattie studiate
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] (ICTRP)

Intervento studiato

Trade Name: Adakveo
Product Name: crizanlizumab
Product Code: SEG101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CRIZANLIZUMAB
Current Sponsor code: SEG101
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 3 (ICTRP)

Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes

Inclusion criteria:
?Male or female patients aged 2 to <18 years (Group 3 will be expanded
to allow enrolment of patients aged 6 to <24 months (and at least 7 kg)
in Part B once the appropriate dose is confirmed in 2 to <6 year old
participants)
?Confirmed diagnosis of sickle cell disease (SCD) (e.g. any genotype
including HbSS, HbSC, HbS?0-thalassemia, HbS?+-thalassemia, and
others) by hemoglobin electrophoresis and/or high performance liquid
chromatography (HPLC) performed locally. Confirmation of diagnosis by
two accepted methods is recommended.
?Experienced at least 1 VOC within the preceding 12 months prior to
screening, as determined by medical history. Prior VOC must have
resolved at least 7 days prior to the first dose in the study and must include all the following:
1.the occurrence of appropriate symptoms (see VOC definition in
protocol Section 7.2.1.1)
2.either a visit to a medical facility or healthcare professional,
3.receipt of oral/parenteral opioid or parenteral NSAIDs.
?If receiving HU/HC, L-glutamine or erythropoietin stimulating agent,
must have been receiving the drug consistently for at least 6 months
prior to Screening and plan to continue taking it at the same dose and
schedule during the trial. Patients who have not been receiving such
drugs must have been off them for at least 6 months prior to screening.
Dose alterations of HU/HC , L-glutamine or erythropoietin stimulating
agent during Part A are not allowed, and if this occurs, the participant
will enter directly to Part B.
?Received standard age-appropriate care for SCD, including penicillin
prophylaxis, pneumococcal immunization, and parental education
? Performance status: Karnofsky = 50% for patients >10 years of age,
and Lansky = 50 for patients = 10 years of age
? Patient must meet the following laboratory values prior to Week 1 Day
1:
? Absolute Neutrophil Count =1.0 x 109/L
? Platelets =75 x 109/L
? Hemoglobin (Hgb) > 5.5 g/dL
? Patient must have adequate renal and hepatic function as defined:
? Estimated Glomerular filtration rate (eGFRe) = 75 mL/min/1.73 m2
using Schwartz formula
? Direct (conjugated) bilirubin = 2.0 x ULN
? Alanine transaminase (ALT) = 3.0 x ULN
?Transcranial Doppler (TCD) for patients aged 2 to < 16 years at time of
screening. with HbSS, HbS?0-thalassemia, and HbSD disease indicating
low risk for stroke (per investigator). Please refer to Section 7.2.2.6 for details.
Other inclusion criteria as per protocol may apply
Are the trial subjects under 18? yes
Number of subjects for this age range: 100
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
(ICTRP)

Exclusion criteria:
?History of stem cell transplant.
?Received any blood products within 30 days prior to Day 1 dosing.
?Plan to participate in a chronic transfusion program (preplanned series of transfusions for prophylactic purposes) or undergo exchange
transfusions/plasmapheresis during the study. Patients requiring
episodic transfusion (simple or exchange) in response to worsened
anemia or VOC are permitted.
?Patients with bleeding disorders
?Contraindication or hypersensitivity to any drug from similar class as
study drug or to any excipients of the study drug formulation.
?Planning to initiate or terminate HU/HC or L-glutamine while on study (except if needed to terminate for safety reasons)
?Patient with active human immunodeficiency virus (HIV) infection
(detectable viral load)
?Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator.
?Patients having taken voxelotor less than 30 days prior to Screening, or planning to take voxelotor while on study are not allowed

Other exclusion criteria as per protocol may apply


Endpoint primari e secondari
Main Objective: - To confirm and establish appropriate dosing of crizanlizumab in patients ages 6 months to <18
years at the time of study entry (Part A and B)
- To evaluate the safety of crizanlizumab in patients ages 6 months to <18 years at the time of study entry (Parts A and B);Secondary Objective: - To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old patients at the time of study entry (Parts A and B)
- To assess other safety measures in patients aged 6 months to < 18 years at the time of study entry
- To characterize long-term PK and PD of crizanlizumab in patients ages 6 months to <18 years at the time of study entry;Primary end point(s): 1.PK (AUCd15) after 1st dose
Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A)

2.PD (AUCd15) after 1st dose
Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A)

3.PK (AUCtau) after multiple dose
Confirm appropriate dosing of Crizanlizumab in participants aged 2 to < 18 years old


4.PD (AUCtau) after multiple dose
Confirm appropriate dosing of Crizanlizumab in participants aged 2 to < 18 years old


5.PK (Cmax) after 1st dose and multiple dose
Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A)


6.PK pre-dose concentrations
Confirm appropriate dosing of crizanlizumab in participants aged 6 months to less than 24 months of age (Part B)


7.Frequency of any adverse events (AEs) as a measure of safety and tolerability
Safety of crizanlizumab in participants aged 6 months to < 18 years (Parts A and B)
;Timepoint(s) of evaluation of this end point: 1. Day 15
2. Day 15
3. Week 15
4. Week 15
5. Week 1 and Week 15
6. Week 1 and Week 19
7. 6 months, 2 years (ICTRP)

Secondary end point(s): 1.Annualized rate VasoOccusive Crisis (VOC) events leading to healthcare visit in clinic/ER/hospital
To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)


2.Annualized rate Vaso Occusive Crisis (VOC) events treated at home (based on documentation by health care provider following phone contact with the patient)
To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)


3.Annualized rate each subcategory of VOC event (uncomplicated pain crisis, acute chest syndrome, hepatic sequestration, splenic sequestration, priapism)
To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)


4.Annualized rate hospitalizations and ER visits (both overall and VOC-related)
To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)


5.Annualized rate days of ER/hospitalization (both overall and VOC-related)
To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)


6.Annualized rate dactylitis events
To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)


7.Number, seriousness, severity, and causality assessments of treatement emergent adverse events and other data as considered appropiate.
To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry


8.Absolute change from baseline in hemoglobin
To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry


9.Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab
To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry


10.Electrocardiogram (ECGs) at relevant PK time points
To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry


11.Growth and sexual maturation assessments (Tanner stage)
To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry


12.PK pre-dose concentrations prior to each study drug dose.
Characterize long-term PK and PD of crizanlizumab in participants aged 6 months to <18 years


13.PD pre-dose concentrations prior to each study drug dose.
Characterize long-term PK and PD of crizanlizumab in participants aged 6 months to <18 years


14.Percentage P-selectin inhibition prior to dosing
Characterize long-term PK and PD of crizanlizumab in participants aged 6 months to <18 years
;Timepoint(s) of evaluation of this end point: 1. 6 months, 2 years
2. 6 months, 2 years
3. 6 months, 2 years
4. 6 months, 2 years
5. 6 months, 2 years
6. 6 months, 2 years
7. 6 months, 2 years
8. 6 months, 2 years
9. Week 1, Week 3, Week 15, Week 27 and End of Treatment (EOT)
10. Screening, Week 7, Week 11, week 15, week 27 and Week 51
11. Screening, Week 51 and End of Treatment (EOT)
12. Week 1, Week 3, Week 7, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51
13. Week 1, Week 3, Week 7, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51
14. Week 3, Week 15, Week 27 and Week 51 (ICTRP)

Data di registrazione
30.11.2018 (ICTRP)

Inclusione del primo partecipante
20.02.2019 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
Medizinischer Infoservice (MCC), infoservice.novartis@novartis.com, +49 911 273-12100?, Novartis Pharma GmbH (ICTRP)

ID secondari
CSEG101B2201, NCT03474965, 2017-001747-12-GB (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001747-12 (ICTRP)