Clinical Trials Register

Summary
EudraCT Number:	2020-005849-16
Sponsor's Protocol Code Number:	KIN001-203
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-10-13
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

Bulgarian Drug Agency

A.2

EudraCT number

2020-005849-16

A.3

Full title of the trial

An 8-week double-blind, randomized, placebo-controlled, phase II study evaluating the effects of oral pamapimod 150 mg with pioglitazone 10 mg daily on COVID-19 development in hospitalized patients infected with SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2)

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

Kinarus COVID-19 Study (KINETIC trial)

A.4.1

Sponsor's protocol code number

KIN001-203

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	Kinarus AG
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	Kinarus AG
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	Kinarus AG
B.5.2	Functional name of contact point	Head Project Management
B.5.3	Address:
B.5.3.1	Street Address	Hochbergerstrasse 60C
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4057
B.5.3.4	Country	Switzerland
B.5.6	E-mail	corinne.peter@kinarus.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	Pioglitazone
D.3.4	Pharmaceutical form	Prolonged-release 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
D.3.9.3	Other descriptive name	PIOGLITAZONE HYDROCHLORIDE
D.3.9.4	EV Substance Code	SUB03834MIG
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	5
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.3.2	Product code	KIN001
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	PAMAPIMOD
D.3.9.1	CAS number	449811-01-2
D.3.9.2	Current sponsor code	KIN001
D.3.9.4	EV Substance Code	SUB32898
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	75
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	Prolonged-release 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	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

COVID-19 development in hospitalized patients infected with SARS-CoV-2

E.1.1.1

Medical condition in easily understood language

Hospitalized patients suffering from 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	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10084272
E.1.2	Term	SARS-CoV-2 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

The primary objective is to evaluate the percentage of participants who die or require non-invasive ventilation / high flow oxygen or invasive mechanical ventilation (including extracorporeal membrane oxygenation (ECMO)) measured in the time frame from Day 0 to week 4 *
* the indication for non-invasive ventilation or high-flow oxygen or invasive mechanical ventilation or ECMO is based on the judgement of the investigator. This includes patients qualifying for any of these therapies but not receiving it for reasons unrelated to the indication, e.g. patient refuses intubation, high-flow or mechanical ventilation or ECMO not available, general condition of patient too bad, etc.

E.2.2

Secondary objectives of the trial

The secondary objectives for this study are:
• Number of ventilator-free days (invasive mechanical ventilation) measured in the time fram from Day 0 to week 4
• Number of invasive, high flow oxygenation, non invasive ventilation and ECMO free days measured in the time frame of Day 0 to week 4
• To evaluate the reduction in mortality or severe respiratory failure as determined by need for high-flow oxygen use and/or invasive/non invasive ventilation techniques and/o ECMO until end of the study (measured at 8 weeks
• To evaluate the all cause mortality measured at 4 and 8 weeks)
• To evaluate the reduction in severe respiratory failure rate as defined by need for high-flow oxygen use and/or invasive/non invasive ventilation techniques and/or ECMO (by number of patients) at 4 weeks and end of study¬ (8 weeks)
• To evaluate the safety and tolerability of pamapimod used in combination with pioglitazone
• To determine length of hospitalization / ICU stay

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Diagnosis of COVID-19 confirmed by a positive test for SARS-CoV-2 RNA by RT PCR in a specimen from the upper respiratory tract, lower respiratory tract or expectorated sputum or by a positive rapid antigen test for SARS-CoV-2
2.Patients hospitalized due to symptomatic COVID-19 infection
a.with a WHO progression score of 4 presenting with at least one of the following co-morbidities: cardiac arrhythmia, arterial hypertension, coronary heart disease, adipositas, chronic renal disease, chronic hepatic disease, active cancer, asthma, COPD, , diabetes mellitus, history of cerebrovascular disease, autoimmune disease, immunosuppression or age > 60 years
or
b. with a WHO progression score of 5 with or without comorbidities
3. Patients being treated or having received off-label agents for COVID-19 (approved for another indication than COVID-19, such as dexamethasone or remdesivir) are eligible for the study
4. Adult male or female patients aged ≥ 18 years
5. Females must have a negative pregnancy test or must be post-menopausal
6. Able to understand and willing to sign an IRB approved written informed consent document. For patients unable to understand and sign themselves, his/her legal representative will be informed and sings the informed consent document in countries where national law/regulations permit.

E.4

Principal exclusion criteria

1. Patients participating in another clinical trial with a new investigational drug or an investigational non-drug treatment
2. Known allergy or intolerance to pamapimod or any other ingredient of the IMP or another P38 inhibitor
3. Known allergy or intolerance of clinical relevance to pioglitazone or any other ingredient of the IMP
4. Patients where oral administration of pioglitazone is contraindicated (i.e. cardiac failure or history of cardiac failure (NYHA stages I to IV), hepatic impairment, diabetic ketoacidosis, current bladder cancer or a history of bladder cancer, uninvestigated macroscopic haematuria
5. Any use of CYP450 2C8 inducers (e.g. rifampicin)
6. Known or suspected active viral (including HIV, hepatitis B, hepatitis C), bacterial, mycobacterial or fungal infection other than COVID-19. Virologic testing not required unless infection is suspected.
7. Pregnant or breastfeeding women
8. Any uncontrolled concurrent illness that would put the patient at a greater risk or limit compliance with the study requirements at the discretion of the investigator
9. Liver enzyme elevation more than 3x above normal
10. Patients who are detained or committed to an institution by a law court or by legal authorities (subject is vulnerable, such as deprived of freedom)

E.5 End points

E.5.1

Primary end point(s)

Percentage of Participants who die or require non-invasive ventilation / high-flow oxygen or invasive mechanical ventilation (including extracorporeal membrane oxygenation (ECMO)) measured in the time frame from Day 0 to week 4

E.5.1.1

Timepoint(s) of evaluation of this end point

4 weeks

E.5.2

Secondary end point(s)

• Number of ventilator-free days (invasive mechanical ventilation) measured in the time frame from D0 to week 4
• Number of invasive ventilation, high-flow oxygenation, non invasive ventilation, and ECMO free days measured in the time frame of Day 0 to week 4
• Reduction in mortality or severe respiratory failure as determined by need for high-flow oxygen use and/or invasive/non invasive ventilation techniques and/or ECMO until end of study (measured at 8 weeks)
• All cause mortality by end of study (measured at 4 and 8 weeks)
• Reduction in severe respiratory failure rate as defined by the need for high-flow oxygen use and/or invasive/non invasive ventilation techniques and/or ECMO at 4 weeks and end of study (8 weeks)
• Safety and tolerability of pamapimod used in combination with pioglitazone
• Length of hospitalization
• Length of ICU stay
• Days free of invasive mechanical ventilation at 4 and 8 weeks
• Total days free of any oxygen supplementation at 4 and 8 weeks
• Clinical Status on Baseline, days 4, 7 and 14 and week 4 and 8 measured by the nine point WHO COVID-19 clinical progression score and EQ5D

E.5.2.1

Timepoint(s) of evaluation of this end point

8 weeks / 4 weeks

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)

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

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

Brazil

Poland

Germany

Russian Federation

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

Trial end is defined as last visit of the last subject 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:

144

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

288

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

For patients unable to understand and sign themselves, his/her legal representative will be informed and signs the informed consent document in countries where this is possible per national laws and regulations.

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

390

F.4.2.2

In the whole clinical trial

432

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 clinical trial for the individual patient, treatment will revert to the standard of care.

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

2021-12-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-11-18

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-10-31

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