Clinical Trials Register

Summary
EudraCT Number:	2021-006951-32
Sponsor's Protocol Code Number:	REP0321
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-02-16
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

Germany - BfArM

A.2

EudraCT number

2021-006951-32

A.3

Full title of the trial

Reparixin 1200 mg three times a day as add-on therapy to standard of care to limit disease progression in hospitalised adult patients with COVID-19
and other community-acquired pneumonia. A multinational, multicentre, randomised, double-blinded, placebo-controlled, parallel-group phase III
trial. (REPAVID-22)

A.3.1

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

Reparixin 1200 mg three times a day as add-on therapy to standard of care to limit disease progression in hospitalised adult patients with COVID-19 and other community-acquired pneumonia.

A.4.1

Sponsor's protocol code number

REP0321

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	Dompé farmaceutici s.p.a.
B.1.3.4	Country	Italy
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	Dompé farmaceutici s.p.a.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Dompé farmaceutici s.p.a.
B.5.2	Functional name of contact point	Clinical Trial Manager
B.5.3	Address:
B.5.3.1	Street Address	Via Santa Lucia 6
B.5.3.2	Town/ city	Milan
B.5.3.3	Post code	20122
B.5.3.4	Country	Italy
B.5.4	Telephone number	0039023408825229
B.5.6	E-mail	fania.ferrari@dompe.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	Reparixin
D.3.2	Product code	DF 1681Y
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	REPARIXIN
D.3.9.1	CAS number	266359-83-5
D.3.9.2	Current sponsor code	DF 1681Y
D.3.9.4	EV Substance Code	SUB130481
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	600
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COVID-19 and other community-acquired pneumonia

E.1.1.1

Medical condition in easily understood language

COVID-19 and other community-acquired pneumonia

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	LLT
E.1.2	Classification code	10010120
E.1.2	Term	Community acquired pneumonia
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objective. To evaluate the efficacy of oral reparixin versus standard care alone in limiting disease progression in adult patients hospitalised for infectious pneumonia acquired in the community (CAP), including COVID-19.

E.2.2

Secondary objectives of the trial

Secondary objectives. To determine the effect of reparixin on several disease severity/progression measures including recovery, ventilatory free days and mortality.
Safety objectives. To evaluate the safety of oral reparixin versus placebo in the specific clinical setting.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Informed consent signed
2. Male and female adults ≥18 years old
3. Patients hospitalised for clinically suspected CAP, defined as the occurrence of (within 48h from hospital admission):
a) at least 1 of the following signs/symptoms: dyspnea, cough, purulent sputum, crackles (rales) and/or rhonchi
b) body temperature > 38°C or <36°C (before or during admission) or leukocytosis (> local ULN)
c) new/increased pulmonary infiltrate(s) by chest imaging
4. Need for non-invasive supplemental oxygen (NIAID-OS 5-6)
5. SpO2 <92% at room air or PaO2 /FiO2 (or SpO2/FiO2) <300
6. Females of child-bearing potential and with an active sexual life must not wish to get pregnant within 30 days after the end of the study and must be using at least one of the following reliable methods of contraception:
a) Hormonal contraception, systemic, implantable, transdermal, or injectable contraceptives from at least 2 months before the screening visit until 30 days after the last Investigational Medicinal Product (IMP) dose
b) A non-hormonal intrauterine device [IUD] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide from at least 2 months before the screening visit until 30 days after the last IMP dose
c) A male sexual partner who agrees to use a male condom with spermicide
d) A sterile sexual partner
Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects, with
child-bearing potential, pregnancy test result must be negative before first drug intake

E.4

Principal exclusion criteria

Patients who meet any of the following criteria are NOT eligible for inclusion in the study:
1. Treatment with IMV or ECMO (NIAID-OS 7);
2. Hepatic dysfunction: ALT or AST > 5 ULN; history of chronic hepatic disease (defined with ChildPugh score B or C);
3. Renal dysfunction: estimated glomerular filtration rate (eGFR, MDRD) <50 mL/min/1.73 m2, or need for haemodialysis or hemofiltration;
4. Current use of >2 immunosuppressive medications or immunosuppression status (AIDS, aplastic anaemia, asplenia, systemic chemotherapy within the past 3 months, neutropenia (ANC < local LLN), solid organ or bone marrow transplant recipients)
5. Treatment with prohibited medication within 5 half-lives, and inability to stop during treatment period (paragraph 5.5.2)
6. Anticipated discharge from the hospital or transfer to another hospital within 72 hours of screening
7. History of:
a. intolerance or hypersensitivity to ibuprofen to more than one medication belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib (hypersensitivity to sulphanilamide antibiotics alone, e.g. sulfamethoxazole does not qualify for exclusion)
b. lactase deficiency, galactosemia or glucose-galactose malabsorption
c. gastrointestinal bleeding or perforation due to previous NSAIDs therapy or recurrent peptic ulcer/haemorrhage
d. allergy to reparixin or any component of the IMP formulation
8. Active bleeding or bleeding diathesis (excluding menses), prior intracranial haemorrhage
9. Participation in other interventional clinical trials
10. Clinical condition not compatible with oral administration of the study drug
11. Pregnancy:
a) positive or missing pregnancy test before first drug intake or day 1;
b) pregnant or lactating women;
Women of childbearing potential and fertile men who do not agree to use at least one primary form of contraception for the duration of the study
12. Current hospital stay >72h
13. Complicated CAP-associated conditions, such as fungal pulmonary infection, tuberculosis infection, abscess, empyema, significant bilateral pleural effusion, massive pulmonary embolism

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients dead or requiring IMV (or ECMO) by day 28

E.5.1.1

Timepoint(s) of evaluation of this end point

By day 28

E.5.2

Secondary end point(s)

Key Secondary endpoints:
- All-cause mortality at day 180
- Proportion of patients alive and discharged at day 28
- Ventilatory-free days at day 28
- Occurrence of IMV (or ECMO) by day 28
- Length of primary hospital stay
Other secondary efficacy endpoints:
- Clinical failure (need for IMV/ECMO or vasopressor, or death) by day 3 and day 7
- 28-day ICU-free days
- Days free of IMV/ECMO (number of days with NIAID-OS 1-6) at day 28
- Duration of antibiotic therapy (days) at day 28
- 28-day hospital free days
- Proportion of patients recovered (downward shift from screening of ≤2 points on the NIAID-OS or live discharge from hospital) at day 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
- Proportion of patients worsening (upward shift from screening of at least >1 point of the NIAID-OS) at day 3, 7±1, 14±2, 21±2, 28 ±2 or at hospital discharge
- PaO2/FiO2, at day 3, 7±1, 14±2, 21±2, 28±2 or at hospital discharge
- All-cause mortality, at by day 28, and day 90
- Hospital re-admission by day 90 and 180
- Time to discharge or to a NEWS of ≤ 2 (for 24 hours), whichever occurs first
- Change in Inflammatory markers (LDH, CRP, ferritin, D-dimer; PCT) and cytokines [at day 3, 7±1, 14±2, 21±2, 28±2 or at hospital discharge]
- Change in quality of life using EQ-5D-5L [90±7 and 180±14 days]
- duration of IMV and/or ECMO at 90 and 180d
- ICU admission and ICU length of stay at 90 and 180d
- hospital length of stay at 90 and 180d
- occurrence of infections at 90 and 180d

E.5.2.1

Timepoint(s) of evaluation of this end point

According to the protocol

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

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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)

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

Argentina

Australia

United States

Austria

Germany

Italy

Türkiye

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

Last assessment of the last patient

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:

150

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

376

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

245

F.4.2.2

In the whole clinical trial

526

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)

After completion of the 180-day assessment or at study termination (for any other reason), patients will receive post-study care as prescribed by their non-study health care provider. No post-study or post study-termination treatment will be provided by the study team or Dompé.

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

2022-03-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-04-14

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

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