Clinical Trials Register

Summary
EudraCT Number:	2021-000068-30
Sponsor's Protocol Code Number:	ECT-001
National Competent Authority:	Lithuania - SMCA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-05-26
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

Lithuania - SMCA

A.2

EudraCT number

2021-000068-30

A.3

Full title of the trial

An open-label, multi-center, phase I/II study of MFA-370 in patients with metastatic urothelial cancer

A.3.1

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

An open-label, multi-center, phase I/II study of MFA-370 in patients with metastatic urothelial cancer

A.3.2

Name or abbreviated title of the trial where available

MANHATTAN

A.4.1

Sponsor's protocol code number

ECT-001

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	Ectin Research AB
B.1.3.4	Country	Sweden
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	Ectin Research AB
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Ectin Research AB
B.5.2	Functional name of contact point	Anna Sjöblom-Hallén
B.5.3	Address:
B.5.3.1	Street Address	AstraZeneca BioVentureHub, Pepparedsleden 1
B.5.3.2	Town/ city	Mölndal
B.5.3.3	Post code	431 83
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46 734-309330
B.5.6	E-mail	anna.sjoblom-hallen@ectinresearch.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	Stromectol
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme BV
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.4	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	IVERMECTIN
D.3.9.1	CAS number	70288-86-7
D.3.9.4	EV Substance Code	SUB12089MIG
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	3
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	Yes
D.2.1.1.1	Trade name	Brufen Retard
D.2.1.1.2	Name of the Marketing Authorisation holder	Mylan Healthcare B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.4	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	IBUPROFEN
D.3.9.1	CAS number	15687-27-1
D.3.9.4	EV Substance Code	SUB08098MIG
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	800
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: 3
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	Ipren
D.2.1.1.2	Name of the Marketing Authorisation holder	McNeil Denmark ApS
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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.3.4	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	IBUPROFEN
D.3.9.1	CAS number	15687-27-1
D.3.9.4	EV Substance Code	SUB08098MIG
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	200
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

Metastatic urothelial cancer

E.1.1.1

Medical condition in easily understood language

Metastatic urothelial cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10064467
E.1.2	Term	Urothelial carcinoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part I: To characterise the safety and tolerability of MFA-370
Part II: To assess the anti-tumor activity of MFA-370

E.2.2

Secondary objectives of the trial

To assess the anti-tumor activity of MFA-370
To characterise the safety and tolerability of MFA-370
To assess survival
To characterise the pharmacokinetic properties of MFA-370

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed Informed Consent Form before any screening procedures
2. ≥ 18 years of age on the day of giving informed consent
3. Confirmed current metastatic urothelial carcinoma of the bladder, including the urethra and upper urinary tract. The patient needs to have progressive disease and/or symptomatic metastatic disease that is unresponsive to standard therapy. The patient must have received all available approved therapies before being eligible for the study unless contraindications or intolerance exist for one or several of them
4. At least one lesion of measurable disease as defined by RECIST1.1 criteria based on CT or MRI scan made within 2 weeks before ibuprofen-start at Day -7
5. World Health Organization (WHO) performance status 0-2
6. Life expectancy ≥12 weeks
7. Patients with reproductive potential will need to use accepted and highly effective means of contraception from study entry until at least 6 weeks for females (women of childbearing potential, WOCP) and 3 months for males after study drug discontinuation

E.4

Principal exclusion criteria

1. Known CNS metastatic lesions, or evidence of impaired blood-brain barrier as assessed by the investigator
2. Have signs or symptoms of active COVID-19 infection or a positive COVID-19 PCR test during the screening period
3. Impaired renal function by estimated Glomerular Filtration Rate (eGFR) <30 ml/min as per local assessment
4. Laboratory values (hematology and biochemistry) within specified ranges to show appropriate organ function
5. Clinically significant cardiac disease,
6. Untreated or uncontrolled hypertension
7. An underlying medical condition that precludes the ability to take oral medication daily
8. Concomitant therapy that precludes enrolment:
- Concomitant use of other nonsteroidal anti-inflammatory drugs (NSAIDs). Wash out and change of treatment is allowed during the screening period and up to one week before visit 2
- Treatment in a prior investigational study within four weeks before enrolment or within five half-lives of the investigational product, whichever is longer, before starting study drug (visit 2)
9. The patient has had biologic, hormonal, anti-neoplastic chemotherapy within 4 weeks prior to screening except for medications with half-lives <5.5 days, or radiation therapy other than palliative treatment within 2 weeks
10. Hypersensitivity to ibuprofen, ivermectin, avermectin, or any of the excipients listed in section 6.1 in respective SmPC
11. Any bleeding disorder or condition where there is an increased risk of bleeding
12. A history of allergic reactions following intake of acetylsalicylic acid or NSAIDs
13. A history of gastrointestinal bleeding or perforation
14. Active or recurrent gastrointestinal ulcer
15. The known or suspected presence of a tropical parasitic infection, such as strongyloidiasis, onchocerciasis, or any other for which treatment with ivermectin is indicated
16. Major surgery within 14 days before enrolment. (Note: trans-urethral resection of bladder tumor is not considered major surgery)
17. For female patients of childbearing potential – pregnancy, as confirmed by a serum pregnancy test at screening, or breast-feeding
18. Any other severe, acute, or chronic medical condition that would interfere with the conduct of the study or interpretation of the study results as judged by the investigator
19. The patient has already participated in the study or been a screening failure

E.5 End points

E.5.1

Primary end point(s)

Part I:
- Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) with a causal relationship to MFA-370
- Tolerability: Incidence of dose interruptions, reductions, and treatment terminations due to AEs/SAEs

Part II:
- Efficacy: Overall Response Rate (ORR) at Week 24, assessed by the investigator based on the assessment of the CT/MR-scans made by the responsible Radiologist at each site (scans assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1)

E.5.1.1

Timepoint(s) of evaluation of this end point

- Safety and tolerability: Continuously up to 30 days safety follow up
- Overall Response Rate: At 24 weeks

E.5.2

Secondary end point(s)

- Anti-tumor activity: ORR, Clinical Benefit Rate (CBR), Progression-Free Survival (PFS), Time to Progression (TTP), Best Overall Response (BOR) (based on CT/MR-scans assessed by Radiologist per RECIST 1.1)
- Safety: Incidence and severity of AEs and SAEs with a causal relationship to MFA-370
- Tolerability: Incidence of dose interruptions, reductions, and treatment terminations due to AEs
- Overall survival (OS)
- Pharmacokinetic (PK) parameters for ibuprofen and ivermectin, including but not limited to; time vs plasma concentration profiles, Cmax, tmax, t1/2

E.5.2.1

Timepoint(s) of evaluation of this end point

- Anti-tumor activity: Every six weeks
- Safety and tolerability: Continuously up to 30 days after last dose
- Overall survival: from the last dose until the date of death
- Pharmacokinetic (PK) parameters: Visit 2, 3, 4, 5, 6, 7, 9, 10, 24

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

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Combination of established medicinal products repositioned as an anti-cancer treatment

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

Six months after the last patient’s completion of Week 24; End of Treatment.

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

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)

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

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)

None

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

2022-07-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-12

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

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