Clinical Trials Register

Summary
EudraCT Number:	2022-002447-22
Sponsor's Protocol Code Number:	C4671031
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-10-03
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2022-002447-22

A.3

Full title of the trial

AN INTERVENTIONAL EFFICACY AND SAFETY, PHASE 2, DOUBLE BLIND, 2 ARM STUDY TO INVESTIGATE ORALLY ADMINISTERED NIRMATRELVIR/RITONAVIR COMPARED WITH PLACEBO/RITONAVIR FOR THE TREATMENT OF SEVERE COVID-19 IN HOSPITALIZED PARTICIPANTS WHO ARE IMMUNOCOMPROMISED OR AT INCREASED RISK FOR SEVERE COVID-19 OUTCOMES

INTERVENČNÉ, DVOJITO ZASLEPENÉ KLINICKÉ SKÚŠANIE FÁZY 2 S 2
RAMENAMI, HODNOTIACE ÚČINNOSŤ A BEZPEČNOSŤ PERORÁLNE PODÁVANÉHO
SKÚŠANÉHO PRODUKTU NIRMATRELVIR/RITONAVIR V POROVNANÍ S
PLACEBOM/RITONAVIROM V LIEČBE ŤAŽKÉHO PRIEBEHU OCHORENIA COVID-19
U HOSPITALIZOVANÝCH IMUNOKOMPROMITOVANÝCH ÚČASTNÍKOV ALEBO
KTORÍ MAJÚ VYSOKÉ RIZIKO ROZVOJA ŤAŽKÉHO PRIEBEHU OCHORENIA
COVID-19

A.3.1

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

A Study to Learn About the Medicine Called Nirmatrelvir Used in Combination With Ritonavir in People with Weakened Immune Systems or at Increased Risk for Poor Outcomes who are Hospitalized Due to Severe COVID-19

A.4.1

Sponsor's protocol code number

C4671031

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	Pfizer 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	Pfizer 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	Pfizer Inc.
B.5.2	Functional name of contact point	Clinical Trials.gov Call Centre
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	10017
B.5.3.4	Country	United States
B.5.4	Telephone number	+18007181021
B.5.6	E-mail	ClinicalTrials.gov_Inquiries@pfizer.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	Yes
D.2.1.1.1	Trade name	RITONAVIR
D.2.1.1.2	Name of the Marketing Authorisation holder	Camber Pharmaceuticals, Inc
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Ritonavir
D.3.4	Pharmaceutical form	Capsule
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	Ritonavir
D.3.9.1	CAS number	155213-67-5
D.3.9.4	EV Substance Code	SUB10342MIG
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	100
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	Nirmatrelvir
D.3.2	Product code	PF-07321332
D.3.4	Pharmaceutical form	Film-coated 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	Nirmatrelvir
D.3.9.3	Other descriptive name	Nirmatrelvir
D.3.9.4	EV Substance Code	SUB220919
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	150
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	Film-coated 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

SARS-CoV-2 Infection

E.1.1.1

Medical condition in easily understood language

COVID-19

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	PT
E.1.2	Classification code	10084460
E.1.2	Term	COVID-19 treatment
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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 effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV-2 viral RNA levels in NP swabs in hospitalized participants ≥12 years of age with severe COVID-19 who are immunocompromised or at increased risk for severe COVID 19 outcomes

E.2.2

Secondary objectives of the trial

•To evaluate the effect of nirmatrelvir/ritonavir compared to placebo/ritonavir treatment on clinical outcomes when added to background usual care, for the treatment of severe COVID 19 in hospitalized participants ≥12 years of age who are immunocompromised or at increased risk for severe COVID 19 outcomes.
•To evaluate the effect of nirmatrelvir/ritonavir compared to placebo/ritonavir on SARS-CoV 2 viral RNA levels in NP swabs in hospitalized participants ≥12 years of age with severe COVID-19 who are immunocompromised or at increased risk for severe COVID 19 outcomes.
•To describe the safety and tolerability of nirmatrelvir/ritonavir relative to placebo/ritonavir for the treatment of severe COVID-19 in hospitalized participants ≥12 years of age who are immunocompromised or at increased risk for severe COVID 19 outcomes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Participants aged 12 years or older and weighing ≥40 kg at screening.
-Refer to Appendix 4 for reproductive criteria and contraception requirements for male (Section 10.4.1) and female (Section 10.4.2) participants.
2. Meeting 1 of the 2 categories of COVID-19 risk: (see Appendix 9, Section 10.9.2).
-Category A: Immunocompromised
-Category B: Non-Immunocompromised, but with ≥2 risk factors
-Onset of signs/symptoms attributable to COVID-19 ≤10 days prior to the day of randomization for non-immunocompromised participants (Category B).
3.Confirmed SARS-CoV-2 infection as determined by RT-PCR or acceptable test method performed by a health care provider (See Appendix 9, Section 10.9.3) in any specimen collected within 48 hours prior to randomization.
4.Hospitalized for inpatient care for the treatment of clinical manifestations of severe COVID-19 (see Appendix 9, Section 10.9.4).
Requirement for oxygen supplementation (via nasal cannula, mask, NIV or high flow oxygen) to maintain SpO2 ≥94% at the time of Screening and Randomization. Participants with chronic lung disease requiring home oxygen therapy are eligible if they require a higher than usual oxygen flow rate to maintain their target oxygen saturation.
5.Requirement for oxygen supplementation (via nasal cannula, mask, NIV or high flow oxygen) to maintain SpO2 ≥94% at the time of Screening and Randomization. Participants with chronic lung disease requiring home oxygen therapy are eligible if they require a higher than usual oxygen flow rate to maintain their target oxygen saturation.

E.4

Principal exclusion criteria

1.Critical illness, defined by ≥1 of the following:
a.Requirement for mechanical ventilation or ECMO at randomization, or likely to require IMV or ECMO within 12 hours of randomization in the judgment of the investigator, or clinical need for mechanical ventilation or ECMO, even if not able to be administered due to resource limitation at the time of randomization.
b.Multi-organ dysfunction/failure.
c.Hemodynamically unstable, eg. septic shock, cardiac failure or requiring vasopressors.
d.Participant not expected to survive 24 hours from time of randomization
2.History of severe chronic liver disease (see Appendix 9, Section 10.9.5).
3.Receiving dialysis of any kind or severe renal impairment defined as eGFR in adults <30 mL/min/1.73 m2 or eCrCl in adolescents aged 12 to 17 years <30 mL/min (see Section 10.7.1 for the recommended formulas).
4.Confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention.
5.History of hypersensitivity or other contraindication to any of the components of the study intervention, as determined by the investigator.
6.Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the patient inappropriate for the study.
7.Use of nirmatrelvir/ritonavir as an outpatient to treat the current COVID 19 related illness ≤7 days of randomization.
8.Current use of any prohibited concomitant medication(s). (See Section 6.9 and Appendix 8).
9.Inability to closely monitor concentrations of immunosuppressant medications (ie, Calcineurin inhibitors and mTOR inhibitors) and adjust their doses for nirmatrelvir/ritonavir DDI during active treatment, and for at least 5 days after the last dose of study intervention.
1.Previous administration with an investigational product (drug or vaccine-) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
11.Known prior participation in this trial.

E.5 End points

E.5.1

Primary end point(s)

•Change from baseline in SARS CoV-2 RNA level in NP swabs at Day 5.

E.5.1.1

Timepoint(s) of evaluation of this end point

•The difference between nirmatrelvir and placebo in mean change from baseline in SARS CoV-2 RNA level in NP swabs 5 days after the start of treatment, regardless of intercurrent events, in the population of hospitalized patients ≥12 years of age with severe COVID-19 who are immunocompromised or at increased risk for severe COVID 19 outcomes.

E.5.2

Secondary end point(s)

•Time to sustained clinical recovery, defined as the first day during the 30 days after randomization in which a participant attains a score of 1, 2, or 3 on the 8-point ordinal scale (ie, remains alive and is either not hospitalized or is hospitalized but no longer requires ongoing inpatient medical care for COVID 19) for at least 7 consecutive days.
•Proportion of participants with death from any cause or initiation of invasive mechanical ventilation or ECMO from baseline (Day 1) through Day 30.
•Proportion of participants with SARS-CoV-2 RNA <LLOQ (defined as <2.0 log10 copies/mL) in NP swabs on Day 15.
•Proportion of participants with sustained NP swab SARS CoV 2 RNA <LLOQ (defined as <2.0 log10 copies/mL) from Day 15 through Day 45.
•Incidence of TEAEs.
•Incidence of SAEs and AEs leading to discontinuations.

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

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)

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

Argentina

Australia

Brazil

Canada

India

Mexico

Puerto Rico

United States

France

Bulgaria

Spain

Germany

Hungary

Slovakia

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 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:

148

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

123

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

Yes

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

Adolescents (12-17 years)

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

116

F.4.2.2

In the whole clinical trial

279

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)

No study intervention will be provided to participants at the end of their study participation. It is expected that participants will be treated as required with standard-of-care treatments, as advised by their usual care physician.

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

2022-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-10-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-02-01

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