Clinical Trials Register

Summary
EudraCT Number:	2020-004840-27
Sponsor's Protocol Code Number:	BO42452
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-09-01
Trial 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

Spain - AEMPS

A.2

EudraCT number

2020-004840-27

A.3

Full title of the trial

A PHASE IB RANDOMIZED, PLACEBO-CONTROLLED STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF CROVALIMAB FOR THE MANAGEMENT OF ACUTE UNCOMPLICATED VASO-OCCLUSIVE EPISODES (VOE) IN PATIENTS WITH SICKLE CELL DISEASE (SCD)

ESTUDIO DE FASE IB, ALEATORIZADO Y CONTROLADO CON PLACEBO PARA EVALUAR LA SEGURIDAD, LA FARMACOCINÉTICA, LA FARMACODINÁMICA Y LA EFICACIA DE CROVALIMAB PARA EL TRATAMIENTO DE LOS EPISODIOS VASOOCLUSIVOS (EVO) NO COMPLICADOS AGUDOS, EN PACIENTES CON ANEMIA DE CÉLULAS FALCIFORMES (ACF)

A.3.1

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

A Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes in Patients with Sickle Cell Disease

Estudio que evalúa la seguridad, farmacocinética, farmacodinámica y eficacia de crovalimab para el tratamiento de episodios vasooclusivos agudos no complicados en pacientes con anemia de células falciformes

A.4.1

Sponsor's protocol code number

BO42452

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	Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
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	F. Hoffman-La Roche Ltd.
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	F.Hoffmann-La Roche Ltd.
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4047
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+349132557300
B.5.5	Fax number	+34913248196
B.5.6	E-mail	spain.start_up_unit@roche.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Crovalimab
D.3.2	Product code	RO7112689/F03-10
D.3.4	Pharmaceutical form	Solution for injection/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	CROVALIMAB
D.3.9.2	Current sponsor code	RO7112689
D.3.9.3	Other descriptive name	C5 inh MAb, SKY59, RO/CH7092230
D.3.9.4	EV Substance Code	SUB197998
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	170
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use

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 (SCD); vaso-occlusive episodes (VOE) in SCD

Enfermedad de células falciformes (SCD); episodios vasooclusivos (VOE) en SCD

E.1.1.1

Medical condition in easily understood language

Sickle cell disease is an inherited red blood cell disorder that affects hemoglobin and leads to painful episodes (also known as vaso-occlusive episodes [VOE]).

La anemia de células falciformes es un trastorno hereditario de los glóbulos rojos que afecta la hemoglobina y conduce a episodios dolorosos (también conocidos como episodios vasooclusivos [VOE]).

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10072397
E.1.2	Term	Vaso-occlusive crisis
E.1.2	System Organ Class	100000004851

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To evaluate the safety of crovalimab compared with placebo

• Evaluar la seguridad de crovalimab en comparación con placebo.

E.2.2

Secondary objectives of the trial

• To evaluate the pharmacokinetics (PK) of crovalimab
• To evaluate the pharmacodynamics (PD) of crovalimab
• To evaluate the efficacy of crovalimab compared with placebo
• To evaluate the immune response to crovalimab

• Evaluar la farmacocinética (PK) de crovalimab
• Evaluar la farmacodinámica (PD) de crovalimab
• Evaluar la eficacia de crovalimab en comparación con placebo.
• Evaluar la respuesta inmune al crovalimab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Signed ICF or Assent Form (as determined by patient’s age and individual site and country standards)
• Age >=12 to =<55 years
• Body weight >=40 kg
• Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia)
• Vaccination against Neisseria meningitidis
• Vaccinations against H. influenzae type B and S. pneumoniae
• Diagnosis of an acute uncomplicated VOE, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics
• Adequate hepatic and renal function
• Hemoglobin >=5 g/dL
• Platelet count >=100,000/µL
• Patients receiving sickle cell therapies must be on a stable dose for >=28 days
• For female patients of childbearing potential, an agreement to remain abstinent or use contraception for 6 months after the dose of study treatment

•Firma del documento de consentimiento o asentimiento informado, según lo determinado por
la edad del paciente y las normas de cada centro y país.
• Edad ≥ 12 y ≤ 55 años
• Peso corporal ≥ 40 kg.
• Diagnóstico confirmado de HbSS o HbS β 0 .
• Vacunación contra Neisseria meningitides.
• Vacunación contra Haemophilus influenzae de tipo B y Streptococcus pneumoniae.
•Diagnóstico de EVO no complicado agudo que requiere ingreso en un hospital o centro
médico de agudos y tratamiento con analgésicos opiáceos parenterales.
• Función adecuada hepatica y renal.
• Hemoglobina ≥ 5 g/dl.
• Recuento de plaquetas ≥ 100.000/ μ l.
• Los pacientes que estén recibiendo tratamientos contra la anemia de células falciformes (
deberán haber recibido una dosis estable durante ≥ 28 días antes
• Mujeres potencialmente fértiles: compromiso de practicar abstinencia sexual o de usar métodos anticonceptivos durante el período de tratamiento y hasta 6 meses después de la última dosis de crovalimab

E.4

Principal exclusion criteria

• More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit
• Pain related to the current VOE ongoing for >48 hours
• Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism
• Pain atypical of an acute uncomplicated VOE
• Evidence of or suspicion of ACS
• Evidence or high suspicion of a severe systemic infection
• Major surgery and/or hospitalization for any reason within 30 days
• History of Neisseria meningitidis infection within 6 months prior
• Known HIV infection with a documented CD4 count <200 cells/µL
• Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol
• Immunized with a live attenuated vaccine within 30 days
• History of hematopoietic stem cell transplant
• Known or suspected hereditary complement deficiency
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 6 months after the study drug administration
• Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within the prior 28 days or within five half-lives of that investigational product, whichever was greater

• Más de 10 EVO en los 12 meses previos a la consulta que hayan requerido visita a un centro médico ,según lo determinado por la historia clínica o por el recuerdo del paciente.

• Dolor relacionado con el EVO actual mantenido durante > 48 horas antes de presentarse el EVO.

• Dolor agudo relacionado con necrosis avascular , secuestro hepático o esplénico o priapismo,
• Dolor atípico de un EVO no complicado agudo
• Signos o sospecha de STA,
• Signos o sospecha elevada de una infección sistémica grave.
• Cirugía mayor y / u hospitalización por cualquier motivo dentro de los 30 días
• Antecedentes de infección por N. meningitidis en los seis meses previos.
• Infección conocida por el VIH con un recuento documentado de linfocitos T CD4 < 200
células/ μ l
• Transfusión o recepción de hemoderivados en los tres meses previos a la presentación del EVO o como parte de un régimen sintomático óptimo para el EVO actual, o participación actual en un protocolo de transfusiones crónicas
• Vacunación con una vacuna de microorganismos vivos atenuados en los 30 días previos a la presentación del EVO.
• Historia del trasplante de células madre hematopoyéticas
• Deficiencia del complemento hereditaria conocida o sospechada
• Embarazo o lactancia materna, o intención de quedarse embarazada durante el estudio o en
los seis meses siguientes a la administración del fármaco del estudio.
• Participación en otro estudio de tratamiento intervencionista con un fármaco experimental o
uso de cualquier tratamiento experimental en los 28 días previos a la presentación del EVO
o en el un período equivalente a cinco semividas de ese producto experimental, lo que sea
mayor.

E.5 End points

E.5.1

Primary end point(s)

1. Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)
2. Change from baseline in targeted vital signs and clinical laboratory test results
3. Incidence and severity of infusion-related reactions and hypersensitivity

1. Incidencia y gravedad de los eventos adversos, con la gravedad determinada de acuerdo con los Criterios de terminología común para eventos adversos del Instituto Nacional del Cáncer (NCI), versión 5.0 (CTCAE v5.0)
2. Cambio con respecto al valor inicial en los signos vitales específicos y los resultados de las pruebas de laboratorio clínico
3. Incidencia y gravedad de las reacciones e hipersensibilidad relacionadas con la perfusión

E.5.1.1

Timepoint(s) of evaluation of this end point

1-3. Up to 84 days

1-3. Hasta 84 días

E.5.2

Secondary end point(s)

1. Serum concentrations of crovalimab over time
2. Relationships between drug exposure and pharmacodynamics, efficacy or safety endpoints of crovalimab
3. Change over time in PD markers (CH50, free C5, sC5b-9)
4. Time to improvement of the primary acute uncomplicated VOE from baseline
5. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study

1. Concentraciones séricas de crovalimab a lo largo del tiempo
2. Relaciones entre la exposición al fármaco y la farmacodinamia, los criterios de valoración de eficacia o seguridad del crovalimab
3. Cambio con el tiempo en los marcadores de DP (CH50, C5 libre, sC5b-9)
4. Tiempo hasta la mejora de la VOE aguda primaria sin complicaciones desde el inicio
5. Prevalencia de anticuerpos antidrogas (ADA) al inicio del estudio e incidencia de ADA durante el estudio

E.5.2.1

Timepoint(s) of evaluation of this end point

1-3. Baseline to Day 84
4. Baseline to hospital discharge (up to 84 days)
5. Baseline to Day 84

1-3. Línea de base al día 84
4. Desde el inicio hasta el alta hospitalaria (hasta 84 días)
5. Visita basal hasta el día 84

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

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase IB

E.7.2

Therapeutic exploratory (Phase II)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

Yes

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

United States

France

Italy

Spain

E.8.7

Trial has a data monitoring committee

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

LPLV or the date at which the last data point is received from the last patient on study, whichever occurs later.

LPLV o la fecha en la que se recibe el último punto de datos del último paciente en estudio, lo que ocurra más tarde

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

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:

F.1.3

Elderly (>=65 years)

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Minors

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

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)

Given only a single interventional dose of study treatment for this study, currently the Sponsor does not have any plans to provide Roche IMP (crovalimab) or any other study Crovalimab treatments to patients who have completed the study. The Sponsor may evaluate whether to continue providing crovalimab in accordance with the Roche Global Policy on Continued Access to Investigational medicinal Product: http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf

Una sola dosis del tratamiento del estudio para este estudio, actualmente el Patrocinador no tiene planes de proporcionar Roche IMP (crovalimab) ni ningún otro tratamiento con Crovalimab del estudio a los pacientes que han completado el estudio. El Patrocinador puede evaluar si continúa proporcionando crovalimab de acuerdo con la Política global de Roche sobre acceso continuo a productos medicinales en investigación: http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf

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

2021-05-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-24

P. End of Trial
P.	End of Trial Status	Ongoing

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