Clinical Trials Register

Summary
EudraCT Number:	2017-003984-37
Sponsor's Protocol Code Number:	CMX001-211
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2018-06-21
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

2017-003984-37

A.3

Full title of the trial

A Randomized, Controlled, Open-Label, Multiple Ascending Dose Study of Intravenous Brincidofovir in Adult Allogeneic Hematopoietic Cell Transplant Recipients with Adenovirus Viremia

Estudio aleatorizado, controlado y abierto sobre la administración por vía intravenosa de dosis múltiples ascendentes de brincidofovir a receptores adultos de trasplante alogénico de células hematopoyéticas con viremia por adenovirus

A.3.1

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

A Study of the Safety of Intravenous Brincidofovir for Adenovirus Infection

Un estudio de la seguridad del Brincidofovir intravenoso para la infección por Adenovirus

A.4.1

Sponsor's protocol code number

CMX001-211

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	Chimerix, Inc
B.1.3.4	Country	United States
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	Chimerix Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Chimerix Inc.
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	2505 Meridian Parkway, Suite 100
B.5.3.2	Town/ city	Durham
B.5.3.3	Post code	NC 27713
B.5.3.4	Country	United States
B.5.4	Telephone number	+19192876006
B.5.5	Fax number	+19198061146
B.5.6	E-mail	CMX001211ivstudy@chimerix.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	EMA/OD/070/16
D.3 Description of the IMP
D.3.1	Product name	Brincidofovir
D.3.2	Product code	CMX001
D.3.4	Pharmaceutical form	Solution for injection
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	Brincidofovir (USAN)
D.3.9.1	CAS number	444805-28-1
D.3.9.2	Current sponsor code	CMX001
D.3.9.3	Other descriptive name	CMX001 / BRINCIDOFOVIR
D.3.9.4	EV Substance Code	SUB130888
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	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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

Treatment of adenovirus infections in adult allogeneic hematopoietic cell transplant recipients

Tratamiento de infecciones por adenovirus en receptores adultos de trasplante alogénico de células hematopoyéticas

E.1.1.1

Medical condition in easily understood language

Treatment of adenovirus infections in adults after allogeneic hematopoietic cell transplant

Tratamiento de infecciones por adenovirus en adultos después del trasplante alogénico de células hematopoyéticas

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10060931
E.1.2	Term	Adenovirus infection
E.1.2	System Organ Class	10021881 - Infections and infestations

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

The main objective is to evaluate the safety and pharmacokinetics (PK) of selected doses of brincidofovir (BCV) administered intravenously (IV) in allogeneic hematopoietic cell transplant (HCT) recipients with adenovirus (AdV) viremia

El objetivo principal es evaluar la seguridad y la farmacocinética (PK) de determinadas dosis de brincidofovir (BCV) administradas por vía intravenosa (i.v.) a receptores de trasplante alogénico de células hematopoyéticas (HCT, por su sigla en inglés) con viremia por adenovirus (AdV).

E.2.2

Secondary objectives of the trial

• To assess the clinical safety of IV BCV with respect to adverse events (AEs) and changes in laboratory parameters.
• To assess PK of BCV and cidofovir (CDV) in plasma and CDV diphosphate (CDV-PP) in peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs) following multiple IV doses of BCV.
• To evaluate the virologic response, based on change from baseline in AdV deoxyribonucleic acid (DNA) in plasma and/or stool and incidence of undetectable AdV viremia, of the selected IV BCV doses in HCT recipients.

•Evaluar la seguridad clínica de BCV i.v. con respecto a los acontecimientos adversos (AEs) y a las variaciones en los parámetros de laboratorio.
•Evaluar la PK de BCV y de cidofovir (CDV) en el plasma y de CDV difosfato (CDV-PP) en los leucocitos mononucleares en la sangre periférica (PBMC) y de los eritrocitos (RBC) tras dosis múltiples de BCV por vía i.v.
•Evaluar la respuesta virológica, mediante la variación del ADN del AdV en plasma o en heces con respecto al valor basal y la incidencia de viremia indetectable del AdV, de las dosis de BVC i.v. concretas en receptores de HCT.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

For inclusion in this study, subjects must:
1. Be ≥ 18-years-old (or per local law or regulations on legal age of consent).
2. Have received an allogeneic HCT within the previous 100 days.
3. Have plasma AdV DNA viremia ≥ 1,000 copies/mL (via quantitative polymerase chain reaction assay; local results must be confirmed by the designated central virology laboratory).

1. Tener ≥18 años (o tener la edad legal para otorgar el consentimiento, en función de los reglamentos locales).
2. Haber recibido un trasplante alogénico de células hematopoyéticas en los 100 días anteriores.
3. Tener una viremia de ADN del AdV ≥1000 copias/ml (medida por reacción en cadena de la polimerasa; los resultados locales deberán confirmarse en el laboratorio de virología central designado).

E.4

Principal exclusion criteria

1. Diarrhea meeting the US National Institutes of Health (NIH)/National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater (i.e., increase of ≥ 4 stools per day over usual pretransplant stool output) within 7 days prior to Day 1.
2. Acute graft versus host disease (GVHD) meeting the following criteria:
: NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea > 1,000 mL/day, or severe abdominal pain with or without ileus) or liver (i.e., bilirubin > 3 mg/dL [SI: > 51 μmol/L]) within 7 days prior to Day 1.
: Any NIH Stage 3 or Stage 4 acute GVHD within 7 days prior to Day 1.
3. Concurrent human immunodeficiency virus or active hepatitis B or C infection.
4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5x the upper limit of the normal reference range (ULN), total bilirubin > 3 mg/dL (SI: > 51 μmol/L), or prothrombin time – international normalized ratio (PT-INR) > 2x ULN within 7 days prior to Day 1.

1. Diarrea de grado 2 o superior de los criterios terminológicos comunes para acontecimientos adversos (CTCAE) de los National Institutes of Health (NIH) y el National Cancer Institute (NCI) de los Estados Unidos (es decir, aumento de ≥4 deposiciones al día con respecto al número de deposiciones habitual antes del trasplante) en los 7 días previos al día 1.
2. Enfermedad de injerto contra huésped (GVHD, por su sigla en inglés) aguda que cumpla los siguientes requisitos:
 -GVHD aguda en estadio 2 o superior de los NIH, intestinal (es decir, diarrea de >1000 ml/día o dolor abdominal intenso, con o sin íleo paralítico) o hepática (es decir, bilirrubina >3 mg/dl [SI: >51 μmol/l]) en los 7 días previos al día 1.
 -GVHD aguda en estadios 3 o 4 de los NIH en los 7 días previos al día 1.
3. Infección simultánea por el virus de la inmunodeficiencia humana o infección activa por los virus de las hepatitis B o C.
4. Elevación de la alanina aminotransferasa (ALT) o de la aspartato aminotransferasa (AST) más de 5 veces por encima del límite superior de la normalidad (LSN), bilirrubina total >3 mg/dl (SI: >51 μmol/l), o tiempo de protrombina – razón normalizada internacional (PT-INR, por sus siglas en inglés) > 2 × LSN en los 7 días previos al día

E.5 End points

E.5.1

Primary end point(s)

To evaluate the safety and pharmacokinetics (PK) of selected doses of brincidofovir (BCV) administered intravenously (IV) in allogeneic hematopoietic cell transplant (HCT) recipients with adenovirus (AdV) viremia

Evaluar la seguridad y la farmacocinética (PK) de determinadas dosis de brincidofovir (BCV) administradas por vía intravenosa (i.v.) a receptores de trasplante alogénico de células hematopoyéticas (HCT, por su sigla en inglés) con viremia por adenovirus (AdV).

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

• Incidence of TEAEs, particularly those of ≥ CTCAE Grade 3 severity and serious adverse events (SAEs).
• Absolute and changes over time in safety laboratory parameters (i.e., hematology and clinical chemistry).
• Plasma BCV Cmax, tmax, AUCτ, AUClast, AUCinf, %AUCextrap, Clast, tlast, t½, CL, Vz, and Vss following Dose 1 and Dose 4, as data permit.
• Change in AdV viremia from baseline.
• Relationship between plasma BCV exposure and virologic endpoints of interest and influence of various covariates of interest on the exposure-response relationships and endpoints.

• Incidencia de TEAEs, sobre todo los de intensidad de grado ≥3 de los CTCAE, y los SAEs.
• Variaciones absolutas y relativas de los parámetros de seguridad de laboratorio en el tiempo (es decir, hematología y bioquímica clínica).
• Cmáx de BCV en plasma, tmáx, AUCτ, AUCúlt, AUCinf, % AUCextrap, Cúlt, túlt, t½, CL, Vz y Vss después de las administraciones 1 y 4, si lo permiten los datos
• Cambio en la viremia AdV desde el inicio.
• Relación entre la exposición al BCV del plasma y los criterios de evaluación virológicos de interés, e influencia de diversas covariables de interés en las relaciones entre exposición y respuesta y los criterios de evaluación

E.5.2.1

Timepoint(s) of evaluation of this end point

Safety: through AEs
Pharmacokinetics: Day 1 and Day 11
Pharmacodynamics: Day 8 and Day 15

Seguridad: a través de AEs
Farmacocinética: Día 1 y Día 11
Farmacodinámica: Día 8 y Día 15

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

Yes

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)

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

Yes

E.8.1.7.1

Other trial design description

Estándar de atención según la elección del médico

Standard of Care as per physician's choice

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Estándar de atención según la elección del médico

Standard of Care as per physician's choice

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

Italy

Spain

United States

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

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

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)

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

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)

Standard of Care as per physician's choice

Estándar de atención según la elección del médico

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

2018-07-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2019-05-09

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