Clinical Trials Register

Summary
EudraCT Number:	2018-003608-38
Sponsor's Protocol Code Number:	CSEG101A2203
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-09-13
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2018-003608-38

A.3

Full title of the trial

A Phase II, multicenter, randomized, open label two arm study comparing the effect of crizanlizumab + standard of care to standard of care alone on renal function in sickle cell disease patients ≥ 16 years with chronic kidney disease due to sickle cell nephropathy (STEADFAST)

Etude de phase II, multicentrique, randomisée, en ouvert, à deux bras de traitement, comparant l’effet du crizanlizumab associé à un traitement standard à celui d’un traitement standard seul sur la fonction rénale de patients âgés d’au moins 16 ans, atteints de drépanocytose avec maladie rénale chronique due à une néphropathie drépanocytaire (STEADFAST)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study exploring the effect of crizanlizumab on kidney function in patients with
chronic kidney disease caused by sickle cell disease

A.3.2

Name or abbreviated title of the trial where available

STEADFAST

A.4.1

Sponsor's protocol code number

CSEG101A2203

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma S.A.S
B.5.2	Functional name of contact point	Information&Communication Médicales
B.5.3	Address:
B.5.3.1	Street Address	8/10 rue Henry Sainte Claire Deville, CS 40150
B.5.3.2	Town/ city	Rueil-Malmaison
B.5.3.3	Post code	92563
B.5.3.4	Country	France
B.5.4	Telephone number	+33 1 5547 6600
B.5.5	Fax number	+33 1 5547 6100
B.5.6	E-mail	icm.phfr@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/12/1034
D.3 Description of the IMP
D.3.1	Product name	crizanlizumab
D.3.2	Product code	SEG101
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CRIZANLIZUMAB
D.3.9.2	Current sponsor code	SEG101
D.3.9.4	EV Substance Code	SUB188615
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Sickle Cell Disease; Sickle Cell Nephropathy

Drépanocytose;
Néphropathie drépanocytaire

E.1.1.1

Medical condition in easily understood language

Sickle Cell Disease; Sickle Cell Nephropathy

Drépanocytose;
Néphropathie drépanocytaire

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10040644
E.1.2	Term	Sickle cell disease
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10002077
E.1.2	Term	Anaemia sickle cell
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on albuminuria (ACR) decrease at 12 months

Evaluer l’effet du crizanlizumab + traitement standard comparé à celui d’un traitement standard seul sur la diminution de l’albuminurie (rapport albumine/créatinine) à 12 mois

E.2.2

Secondary objectives of the trial

- Evaluate the effect of crizanlizumab (SEG101) + standard of care (SOC) compared to SOC alone on change in albuminuria (ACR)
- Evaluate the effect of SEG101 + SOC compared to SOC alone on albuminuria (ACR) decrease at 6 m
- Evaluate the effect of SEG101 + SOC compared to SOC alone on protein to creatinine ratio (PCR) at 12 m
- Evaluate the effect of SEG101 + SOC compared to SOC alone on the percentage change in eGFR
- Evaluate the effect of SEG101 + SOC compared to SOC alone on ACR decline rate
- Evaluate the effect of SEG101 + SOC compared to SOC alone on eGFR decline rate
- Evaluate the effect of SEG101 + SOC compared to SOC alone on the progression of CKD at 12m
- Evaluate overall safety and, tolerability of SEG101 + SOC compared to SOC alone
- Assess the immunogenicity of SEG101 over the study period (treatment of 1y + 105d follow-up)
- Evaluate healthcare resource utilization (visits to emergency room [ER] and
hospitalizations) in SEG101 + SOC arm compared to SOC alone

Evaluer l’effet du SEG101+traitement standard comparé à celui d’un traitement standard seul sur:
-les variations de l’albuminurie (rapport albumine/créatinine)
-la diminution de l’albuminurie (rapport albumine/créatinine) à 6 mois
-le rapport protéine/créatinine à 12 mois
-le pourcentage de variation du DFG estimé
-le taux de diminution du rapport albumine/creatinine
-le taux de diminution du DFG estimé
-la progression de la maladie rénale chronique à 12 mois
Evaluer la tolérance et l’innocuité du SEG101+traitement standard comparé au traitement standard seul
Evaluer l’immunogénicité du SEG101 sur la période de l’étude (1 an de traitement + 105 jours de suivi)
Evaluer le recours aux services hospitaliers (visites aux urgences et hospitalisations) dans le bras SEG101 + traitement standard comparé au bras traitement standard seul

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

o Confirmed diagnosis of SCD (HbSS and HbSβ0-thal SCD genotypes are eligible)
o Patients with eGFR ≥ 45 to ≤ 120 mL/min/1.73 m2 based on CKD EPI formula
o Patients with ACR of ≥ 100 to < 2000 mg/g
o Receiving standard of care drug(s) for SCD for at least 6 months prior to study entry
o Written informed consent (or assent/ parental consent for minor subjects) prior to any screening procedures

Additional inclusion criteria as per full protocol may apply

o Patients atteints de drépanocytose dont le diagnostic a été confirmé (localement) par électrophorèse de l’hémoglobine ou par chromatographie liquide à haute performance (HPLC). Les génotypes homozygotes HbSS et hétérozygotes HbSβ0-thal sont éligibles.
o Patients ayant un DFG estimé ≥ 45 et ≤ 120 ml/min/1,73 m² d’après la formule CKD-EPI (pour Chronic Kidney Disease Epidemiology Collaboration).
o Patients ayant un rapport albumine/créatinine ≥ 100 et < 2000 mg/g.
o Patients recevant un ou plusieurs médicaments standards contre la drépanocytose et/ou une maladie rénale chronique. Les patients traités par HU/HC, IEC et/ou ARA II (et qui présentent toujours un rapport albumine/créatinine anormal malgré le traitement) doivent avoir reçu ce ou ces traitements depuis au moins les 6 mois précédant l’inclusion dans l’étude et prévoir de poursuivre à la même posologie jusqu’à la fin de l’étude.
o Le consentement éclairé doit être obtenu par écrit avant toute participation à l’étude.

Des critères d'inclusion supplémentaires peuvent être appliqués conformément au protocole complet

E.4

Principal exclusion criteria

o History of stem cell transplant - Patients with evidence of AKI within 3 months of study entry
o Blood pressure > 140/90 mmHg despite treatment
o Patients undergoing hemodialysis
o Received blood products within 30 days of Week 1 Day 1
o Participating in a chronic transfusion program
o History of kidney transplant
o Patients with hypoalbuminemia

Additional protocol-defined exclusion criteria may apply

o Patients ayant eu une atteinte rénale aiguë documentée dans les 3 mois précédant l’inclusion dans l’étude.
o Tension artérielle > 140/90 mmHg malgré un traitement.
o Patients sous hémodialyse.
o Patients ayant reçu un produit sanguin dans les 30 jours précédant le Jour 1 de la Semaine 1.
o Patients participant à un programme de transfusions sanguines régulières (série de transfusions planifiée à l’avance à visée prophylactique). Les transfusions occasionnelles reçues du fait de complications aiguës sont autorisées (syndrome thoracique aigu, séquestration splénique aiguë, séquestration hépatique aiguë, aggravation de l’anémie).
o Antécédents de greffe de reins.
o Patients atteints d’hypoalbuminémie.

Des critères d'exclusion définis par protocole supplémentaires peuvent s'appliquer

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with ≥ 30% decrease in ACR at 12 months compared to baseline

Proportion de patients présentant une diminution ≥ 30 % du rapport albumine/créatinine après 12 mois de traitement par rapport à la baseline

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline and Week 53 Day 1

Baseline et Semaine 53 Jour 1

E.5.2

Secondary end point(s)

1. Mean change in ACR
2. Proportion of patients with ≥ 30% decrease in ACR
3. Proportion of patients with ≥ 20% improvement of PCR
4. Proportion of patients with a stable (within ± 20% change) PCR
5. Percentage change in eGFR
6. Slope of ACR decline based on ACR values
7. Slope of eGFR decline based on eGFR values
8. Proportion of patients with progression of CKD
9. Safety will be assessed by the frequency and severity of adverse events (AEs), deaths, SAEs, and laboratory abnormalities
10. Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab
11. PK parameters will accompany immunogenicity measurements to evaluate the impact of immunogenicity on exposure (PK)
12. Annualized rate of visits to ER and hospitalizations due to AKI events, VOCs, or other SCD complications

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Baseline, Week 15 Day 1, Week 27 Day 1, Week 39 Day 1, Week 53 Day 1
2. Baseline, Week 27 Day 1
3. Baseline and Week 53 Day 1
4. Baseline and Week 53 Day 1
5. Baseline, Week 15 Day 1, Week 27 Day 1, Week 39 Day 1, Week 53 Day 1
6. Baseline, Week 15 Day 1, Week 27 Day 1, Week 39 Day 1, Week 53 Day 1
7. Baseline, Week 15 Day 1, Week 27 Day 1, Week 39 Day 1, Week 53 Day 1
8. Baseline and Week 53 Day 1
9. all timepoints
10. Week 1 Day 1, Week 3 Day 1, Week 11 Day 1, Week 23 Day 1, Week 39 Day 1, Week 53 Day 1, 105 Day follow-up
11. Week 1 Day 1, Week 3 Day 1, Week 11 Day 1, Week 23 Day 1, Week 39 Day 1, Week 53 Day 1, 105 Day follow-up
12. all timepoints

1.Baseline,semaine 15 jour 1,semaine 27 jour 1,semaine 39 jour 1, emaine 53 jour 1
2.Baseline,semaine 27 jour 1
3.Baseline et semaine 53 jour 1
4.Baseline et semaine 53 jour 1
5.Baseline,semaine 15 jour 1,semaine 27 jour 1,semaine 39 jour 1,semaine 53 jour 1
6.Baseline,semaine 15 jour 1,semaine 27 jour 1,semaine 39 jour 1,semaine 53 jour 1
7.Baseline,semaine 15 jour 1,semaine 27 jour 1,semaine 39 jour 1,semaine 53 jour 1
8.Baseline et semaine 53 jour 1
9.Tous les critère d’évaluation
10.Semaine 1 Jour 1,Semaine 3 Jour 1, Semaine 11 Jour 1, Semaine 23 Jour 1, Semaine 39 Jour 1, Semaine 53 Jour 1, Suivi de 105 jours
11.Semaine 1 Jour 1,Semaine 3 Jour 1, Semaine 11 Jour 1, Semaine 23 Jour 1, Semaine 39 Jour 1, Semaine 53 Jour 1, Suivi de 105 jours
12.Tous les critère d’évaluation

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

healthcare resource utilization, immunogenicity

utilisation des ressources de santé, immunogénicité

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

Egypt

France

Ghana

Greece

India

Italy

Kenya

Lebanon

Netherlands

Panama

South Africa

Spain

Turkey

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

160

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

170

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will be allowed post trial access (PTA) to study treatment, i.e. the provision of a product, either investigational treatment or comparator, to participants following trial completion. PTA continues until the investigational treatment receives regulatory approval, is commercially available and a reimbursement decision has been made in the patient’s country, or patient is no longer deriving benefit per the investigator’s evaluation. PTA must comply with the local laws and regulations.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-10-31

Ethics Committee Opinion of the trial application

Not-Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-12-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-03-20

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