Clinical Trials Register

Summary
EudraCT Number:	2020-005366-34
Sponsor's Protocol Code Number:	WV43042
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-04-20
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2020-005366-34

A.3

Full title of the trial

A PHASE II RANDOMIZED, DOUBLE-BLIND,
PLACEBO-CONTROLLED STUDY TO EVALUATE
THE ANTIVIRAL ACTIVITY, SAFETY,
PHARMACOKINETICS, AND EFFICACY OF
RO7496998 (AT-527) IN
NON-HOSPITALIZED ADULT PATIENTS WITH
MILD OR MODERATE COVID-19

ESTUDIO DE FASE II, ALEATORIZADO, DOBLE CIEGO Y CONTROLADO CON PLACEBO PARA EVALUAR LA ACTIVIDAD ANTIVIRAL, LA SEGURIDAD, LA FARMACOCINÉTICA Y LA EFICACIA DE RO7496998 (AT-527) EN PACIENTES ADULTOS NO HOSPITALIZADOS CON COVID-19 LEVE O MODERADA

A.3.1

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

A Study to Evaluate the Antiviral Activity, Safety, Pharmacokinetics, and Efficacy of RO7496998 (AT-527) in Non-Hospitalized Adult Patients with Mild or Moderate COVID-19

Estudio para evaluar la actividad antiviral, seguridad, farmacocinética y eficacia en pacientes adultos no hospitalizados con Covid-18 o moderada.

A.3.2

Name or abbreviated title of the trial where available

Phase II virology covid study

A.4.1

Sponsor's protocol code number

WV43042

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	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.Hoffmann-La Roche, Ltd.
B.4.2	Country	Switzerland
B.4.1	Name of organisation providing support	Atea Pharmaceuticals Inc. (material support)
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	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	4070
B.5.3.4	Country	Switzerland
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	AT-527
D.3.2	Product code	RO7496998
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available yet
D.3.9.1	CAS number	2241337-84-6
D.3.9.2	Current sponsor code	RO7496998 (AT-527)
D.3.9.3	Other descriptive name	AT-511 HEMI-SULFATE SALT
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	550
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.IMP: 2
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	AT-527
D.3.2	Product code	RO7496998/F10-02
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available yet
D.3.9.1	CAS number	2241337-84-6
D.3.9.2	Current sponsor code	RO7496998(AT-527)
D.3.9.3	Other descriptive name	AT-511 HEMI-SULFATE SALT
D.3.9.4	EV Substance Code	SUB207005
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	275
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Coronavirus disease 2019 (COVID-19)

Enfermedad de Coronavirus 2019 (Covid-19)

E.1.1.1

Medical condition in easily understood language

COVID-19 is a respiratory tract infection caused by a new type of coronavirus

Covid-19 es una infección del tracto respiratorio causado por un nuevo tipo de coronavirus.

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	23.1
E.1.2	Level	LLT
E.1.2	Classification code	10084401
E.1.2	Term	COVID-19 respiratory infection
E.1.2	System Organ Class	100000004862

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 antiviral activity of AT-527 compared with placebo based on change from baseline in amount of SARS-CoV-2 virus RNA

Evaluar la actividad antiviral de (AT-527), en comparación con un placebo, con respecto al momento basal de la cantidad de ARN del virus SARS-CoV-2.

E.2.2

Secondary objectives of the trial

• To evaluate the antiviral activity of AT 527 compared with placebo based on time to cessation of SARS-CoV-2 viral shedding, time to sustained non-detectable SARS-CoV-2 virus RNA, proportion of patients positive for SARS-CoV-2 virus RNA, and area under the curve in the amount of SARS-CoV-2 virus RNA
• To evaluate the safety of AT 527 compared with placebo
• To characterize the PK profile of AT-511 (free base form of AT 527) and its major metabolites
• To evaluate the relationship between drug exposure and antiviral activity of AT-527
• To evaluate the efficacy of AT 527 compared with placebo

-Evaluar la actividad antiviral de AT-527 en comparación con un placebo basado en tiempo transcurrido hasta el cese de la excreción viral de SARS-CoV-2, tiempo transcurrido hasta la persistencia de ARN del virus SARS-CoV-2 no detectable, proporción de pacientes con positividad de ARN del virus SARS-CoV-2 mediante RT-PCR en los momentos especificados.
-Evaluar la seguridad de AT-527 en comparación con un placebo.
-Caracterizar el perfil FC de AT-511 (forma de base libre de AT-527) y sus metabolitos principales.
-Evaluar la relación entre la exposición al fármaco y la actividad antiviral de AT-527.
-Evaluar la eficacia de AT-527 en comparación con un placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age>=18 years at time of signing Informed Consent Form
• Positive SARS-CoV-2 diagnostic test (RT-PCR or rapid antigen test) at screening
• Has symptoms consistent with mild or moderate COVID-19, as determined by the investigator, with onset <=5 days prior to randomization
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception, during the treatment period and for 30 days after the final dose of AT-527.

- Edad ≥18 años en el momento de firmar el documento de consentimiento informado.
- Prueba diagnóstica positiva para SARS-CoV-2 ( [RT-PCR] o prueba rápida de antígenos) en la selección
- Síntomas compatibles con COVID-19 leve o moderada, según lo determinado por el investigador, que hayan aparecido <=5 días antes de la aleatorización.
- Mujeres en edad fértil: compromiso de practicar la abstinencia sexual (abstenerse de mantener relaciones heterosexuales) o de utilizar métodos anticonceptivos adecuados durante el período de tratamiento y durante 30 días después de la última dosis de AT-527.

E.4

Principal exclusion criteria

Clinical signs indicative of COVID-19 illness requiring hospitalization, defined as any of the following: shortness of breath at rest, respiratory rate >= 30, heart rate >= 125, peripheral capillary oxygen saturation (SpO2) <= 93% on room air
• Treatment with a therapeutic agent against SARS-CoV-2 including, but not limited to, other direct-acting antivirals, convalescent plasma, monoclonal antibodies against SARS-CoV-2, or intravenous immunoglobulin within 3 months or less than 5 drug-elimination half-lives (whichever is longer) prior to screening
• Requirement, in the opinion of the investigator, for any of the prohibited medications during the study
• Use of hydroxychloroquine or amiodarone within 7 days of screening
• Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the final dose of AT-527. Women of childbearing potential must have a negative serum pregnancy test result at screening
Abnormal laboratory test results at screening
• Clinically significant abnormal ECG, as determined by the Investigator, at screening
• Planned procedure or surgery during the study
• Known allergy or hypersensitivity to study drug or drug product excipients
• Substance abuse, as determined by the investigator, within 12 months prior to screening
• Poor peripheral venous access
• Malabsorption syndrome or other condition that would interfere with enteral absorption
Any clinically significant history of epistaxis within the last 3 months and/or history of being hospitalized due to epistaxis of any previous occasion
• History of anaphylaxis
• Any uncontrolled serious medical condition or other clinically significant abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

- Signos clínicos indicativos de enfermedad por COVID-19 con necesidad de hospitalización, definidos como cualquiera de las circunstancias siguientes: dificultad respiratoria en reposo, frecuencia respiratoria >= 30, frecuencia cardíaca >= 125, saturación de oxígeno en sangre capilar periférica>= 93 % con aire ambiente.
- Tratamiento con un fármaco contra el SARS-CoV-2, por ejemplo, otros antivirales de acción directa, plasma de convalecientes, anticuerpos monoclonales contra el SARS-CoV-2 o inmunoglobulinas intravenosas en los 3 meses o el equivalente a menos de 5 semividas de eliminación del fármaco (lo que suponga más tiempo) previos a la selección.
- Necesidad, en opinión del investigador, de cualquiera de los medicamentos no permitidos durante el estudio.
- Uso de hidroxicloroquina o amiodarona en los 7 días previos a la selección.
- Embarazo o lactancia, o intención de quedarse embarazada durante el estudio o en los 30 días siguientes a la última dosis de AT-527. Las mujeres en edad fértil deberán dar negativo en una prueba de embarazo en orina realizada durante el período de selección.
- Resultados analíticos anómalos en la selección.
- Anomalías clínicamente significativas en el ECG, conforme al criterio del investigador, durante el período de selección.
- Procedimiento o intervención quirúrgica programada durante el estudio.
- Alergia o hipersensibilidad conocidas al fármaco del estudio o a sus excipientes.
- Abuso de sustancias, conforme al criterio del investigador, en los 12 meses previos a la selección.
- Acceso venoso periférico difícil.
- Síndrome de malabsorción u otro trastorno que pueda interferir en la absorción intestinal.
- Antecedentes clínicamente significativos de epistaxis en los 3 últimos meses y/o antecedentes de hospitalización por epistaxis en cualquier episodio previo.
- Antecedentes de anafilaxia.
- Cualquier enfermedad grave no controlada u otra anomalía clínicamente significativa en los análisis clínicos que, en opinión del investigador, impida la participación segura del paciente en el estudio y su finalización.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in amount of SARS-CoV-2 virus RNA as measured by RT-PCR at specified timepoints

Variación con respecto al momento basal de la cantidad de ARN del virus SARS-CoV-2 medida mediante RT-PCR en los momentos especificados.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. Baseline (Day 1) to Day 7

1. Momento basal (día 1) a Día 7.

E.5.2

Secondary end point(s)

1.Time to cessation of SARS-CoV-2 viral shedding as measured by RT-PCR
2. Time to sustained non-detectable SARS-CoV-2 virus RNA
3. Proportion of patients positive for SARS-CoV-2 virus RNA by RT-PCR at specified timepoints
4. Area under the curve in the amount of SARS-CoV-2 virus RNA as measured by RT-PCR
5. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0
6. Change from baseline in targeted vital signs, including SpO2
7. Change from baseline in targeted clinical laboratory test results
8. Plasma concentration of AT-511, AT-551, AT-229, and AT-273 (surrogate for the intracellular concentration of the active triphosphate metabolite AT-9010) at specified timepoints
9. The time to alleviation or improvement of COVID-19 symptoms (Items 1-12 of the COVID-19 symptom diary) maintained for a duration of 21.5 hours
10. Time to alleviation of COVID-19 symptoms
11. Duration of fever
12. Frequency of COVID-19-related complications
13. Time to alleviation of an individual symptom

1.Tiempo transcurrido hasta el cese de la excreción viral de SARS-CoV-2 determinado mediante RT-PCR.
2.Tiempo transcurrido hasta la persistencia de ARN del virus SARS-CoV-2 no detectable.
3.Proporción de pacientes con positividad de ARN del virus SARS-CoV-2 mediante RT-PCR en los momentos especificados.
4. Área bajo la curva de la cantidad de ARN del virus SARS-CoV-2 determinado mediante RT-PCR.
5. Incidencia e intensidad de los acontecimientos adversos, con determinación de la intensidad conforme a los criterios CTCAE del NCI, v5.0.
6.Variación de las constantes vitales de interés, incluida la SpO2, con respecto al momento basal.
7. Variación de los resultados analíticos de interés con respecto al momento basal.
8. Concentración plasmática de AT-511, AT-551, AT-229 y AT-273 (marcador indirecto de la concentración intracelular del metabolito trifosfato activo AT-9010) en los momentos especificados.
9.Tiempo hasta el alivio de los síntomas de COVID-19, Puntuación de 0 o 1 en los apartados 1−12 del Diario de síntomas de COVID-19, mantenido durante al menos 21,5 horas
10.Tiempo hasta el alivio de síntomas de Covid-19.
11. Duración de la fiebre.
12. Frecuencia de las complicaciones relacionadas con Covid-19.
13.Tiempo hasta el alivio de un síntoma específico.

E.5.2.1

Timepoint(s) of evaluation of this end point

1-4. Day 1 to Day 7
5. Up to Day 33
6. Baseline to Day 7
7. Baseline to Day 7
8. Day 1 to Day 7
9-13. Day 1 to Day 28

1-4 Día 1 a día 7.
5. Hasta día 33.
6. Momento basal a día 7.
7. Momento basal a día 7.
8. Día 1 a día 7.
9-13. Día 1 a día 28.

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

Yes

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

Yes

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

Bulgaria

Ireland

Poland

Spain

United Kingdom

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

UVUP

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:

198

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

190

F.4.2.2

In the whole clinical trial

220

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)

Currently, the Sponsor does not have any plans to provide Roche IMP (RO7496998
[AT-527]) or any other study treatments to patients who have completed the study. The
Sponsor may evaluate whether to continue providing AT-527 in accordance with the
Roche Global Policy on Continued Access to Investigational Medicinal Product, available
at the following website:
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

2021-06-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-03-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-10-13

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