Clinical Trials Register

Summary
EudraCT Number:	2023-000171-13
Sponsor's Protocol Code Number:	P23
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2023-03-06
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

Netherlands - Competent Authority

A.2

EudraCT number

2023-000171-13

A.3

Full title of the trial

SGM-101 tumor-targeted fluorescence endoscopy to enable discrimination of malignant from benign tissue in rectal polyps with suspected T1 adenocarcinoma or high grade dysplasia: a feasibility study

SGM-101 tumor-gerichte fluorescentie-endoscopie om kwaadaardig van goedaardig weefsel te kunnen onderscheiden in rectale poliepen met vermoedelijk T1 adenocarcinoom of hooggradige dysplasie: een haalbaarheidsstudie.

A.3.1

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

Discriminating malignant from benign tissue in rectal polyps with the help of the fluorescent probe SGM-101

Onderscheid tussen kwaadaardig en goedaardig weefsel in rectale poliepen met behulp van de fluorescerende stof SGM-101

A.3.2

Name or abbreviated title of the trial where available

SGM-T1

A.4.1

Sponsor's protocol code number

P23

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	leiden university medical center
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Leiden University Medical Center
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Leiden University Medical Center
B.5.2	Functional name of contact point	Denise Hilling
B.5.3	Address:
B.5.3.1	Street Address	Albinusdreef 2
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333ZA
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715264005
B.5.6	E-mail	d.e.hilling@lumc.nl

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	Fluorochrome-labeled anticarcinoembryonic antigen
D.3.2	Product code	SGM-101
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SGM-101
D.3.9.3	Other descriptive name	Chimeric monoclonal antibody against carcinoembryonic antigen conjugated to fluorochrome BM-104
D.3.9.4	EV Substance Code	SUB294627
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
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	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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

Early rectal cancer/ big polyps with suspected T1 rectal cancer.

Vroegstadium endeldarmkanker / endeldarmpoliep verdacht om ook een T1-component te bezitten.

E.1.1.1

Medical condition in easily understood language

Rectal polyp with suspected rectal cancer

endeldarmpoliep met een plekje verdacht voor kanker

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10038074
E.1.2	Term	Rectal polyp
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

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 main objective is to investigate the feasibility of a tumour-targeted fluorescent tracer SGM-101, combined with the use of the CE-marked fluorescence-laparoscope of Quest Medical Imaging, to discriminate between normal, LGD and malignant tissue (HGD, T1RC) in patients with suspected T1/HGD rectal cancer.
It consists of two phases for which primary objectives are defined separately:
Phase I: Dose optimization phase to determine the optimal dose of SGM-101
Phase II: feasibility assessment of tumor-targeted fluorescence endoscopy with the use of SGM-101 in discriminating normal, LGD and malignant tissue (HGD, T1RC).

Het hoofddoel is de haalbaarheid te onderzoeken van een tumor-gerichte fluorescerende tracer SGM-101, gecombineerd met het gebruik van de CE-gemarkeerde fluorescentie-laparoscoop van Quest Medical Imaging, om onderscheid te maken tussen normaal, LGD en kwaadaardig weefsel (HGD, T1RC) bij patiënten met vermoedelijke T1/HGD rectumkanker.
Het bestaat uit twee fasen waarvoor de primaire doelstellingen afzonderlijk worden gedefinieerd:
Fase I: Dosisoptimalisatiefase om de optimale dosis van SGM-101 te bepalen
Fase II: beoordeling van de haalbaarheid van tumorgerichte fluorescentie-endoscopie met het gebruik van SGM-101 bij het onderscheiden van normaal, LGD en kwaadaardig weefsel (HGD, T1RC).

E.2.2

Secondary objectives of the trial

-To assess the ex-vivo tumour-to-background ratio (TBR) and dysplasia-to-background ratio (DBR) (ex-vivo TDR already encountered within main objective)
-To assess the in-vivo TDR, TBR and DBR
-To assess the accuracy of SGM-101 to discriminate HGD/T1RC from LGD ex-vivo.
-To assess the accuracy of SGM-101 to discriminate HGD/T1RC from LGD in-vivo.
- To assess the feasibility of SGM-101 to predict depth of cancerous invasion.
-Feasibility of SGM-101 to discriminate between R0 and R1 resections.
- The correlation between serum CEA expression to ex-vivo TDR, TBR and DBR
- To assess whether the tissue CEA expression corelates to the accompanying fluorescent signal.

-de ex-vivo tumor-achtergrondverhouding (TBR) en de dysplasie-achtergrondverhouding (DBR) beoordelen (de ex-vivo TDR is al aan bod gekomen in het hoofddoel).
-beoordelen van de in-vivo TDR, TBR en DBR
-Beoordelen van de nauwkeurigheid van SGM-101 om HGD/T1RC ex-vivo te onderscheiden van LGD.
-Beoordelen van de nauwkeurigheid van SGM-101 om HGD/T1RC te onderscheiden van LGD in-vivo.
- Beoordelen van de haalbaarheid van SGM-101 om de diepte van de kankerinvasie te voorspellen.
-Haalbaarheid van SGM-101 om onderscheid te maken tussen R0 en R1 resecties.
- De correlatie tussen serum CEA-expressie en ex-vivo TDR, TBR en DBR.
- Nagaan of de weefsel CEA-expressie correleert met het begeleidende fluorescentiesignaal.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1. Patient must have suspected HGD/T1RC and scheduled for a local endoscopic en-bloc resection. The rectum is defined as the area between the linea dentata and 10cm ab ano.
2. Age > 18 years old
3. Patients should be capable and willing to give signed informed consent before study specific procedures.

Om in aanmerking te komen voor deelname aan deze studie moet een proefpersoon aan alle volgende criteria voldoen:
1. De patiënt moet vermoedelijk HGD/T1RC hebben en gepland zijn voor een lokale endoscopische en-bloc-resectie. Het rectum wordt gedefinieerd als het gebied tussen de linea dentata en 10 cm ab ano.
2. Leeftijd > 18 jaar
3. De patiënten moeten in staat en bereid zijn om vóór de studiespecifieke procedures een ondertekende geïnformeerde toestemming te geven.

E.4

Principal exclusion criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study

1. Prior participation in this study
2. Previous administration of SGM-101
3. Patients with a history of anaphylactic shock
4. Patients pregnant or breastfeeding, lack of effective contraception in male or female patients with reproductive potential
5. Any condition that the investigator considers to be potentially jeopardizing the patients’ well-being or the study objectives.

Een potentiële proefpersoon die voldoet aan een van de volgende criteria wordt uitgesloten van deelname aan dit onderzoek

1. Eerdere deelname aan dit onderzoek
2. Eerdere toediening van SGM-101
3. Patiënten met een voorgeschiedenis van anafylactische shock
4. Patiënten die zwanger zijn of borstvoeding geven, gebrek aan effectieve anticonceptie bij mannelijke of vrouwelijke patiënten met reproductieve mogelijkheden
5. Elke aandoening die volgens de onderzoeker het welzijn van de patiënten of de doelstellingen van het onderzoek in gevaar kan brengen.

E.5 End points

E.5.1

Primary end point(s)

The ex-vivo T1RC/HGD to LGD ratio, in this manuscript named as the tumour-to-dysplasia ratio (TDR).
The reason to choose ex-vivo instead of in-vivo TDR as main endpoint is because during ex-vivo imaging it is possible to accurately correlate fluorescent signal with tissue pathology (normal tissue, LGD, HGD/T1RC) in a standardized manner. This will be analyzed with a dedicated 700nm NIR-fluorescence scanner.

De ex-vivo T1RC/HGD tot LGD ratio, in dit manuscript de tumor-dysplasie ratio (TDR) genoemd.
De reden om ex-vivo in plaats van in-vivo TDR als belangrijkste eindpunt te kiezen is dat het tijdens ex-vivo beeldvorming mogelijk is om fluorescentiesignaal nauwkeurig te correleren met weefselpathologie (normaal weefsel, LGD, HGD/T1RC) op een gestandaardiseerde manier. Dit zal worden geanalyseerd met een speciale 700nm NIR-fluorescentiescanner.

E.5.1.1

Timepoint(s) of evaluation of this end point

During surgery in vivo pictures are made
After surgery ex vivo pictures are performed.
Subsequently the images and accompanying data can be analysed

Tijdens de operatie worden in vivo foto's gemaakt
Na de operatie worden ex vivo foto's gemaakt.
Vervolgens kunnen de beelden en de bijbehorende gegevens worden geanalyseerd

E.5.2

Secondary end point(s)

-Ex-vivo tumour-to-background ratio (TBR) and dysplasia-to-background ratio (DBR) (ex-vivo TDR already encountered within main objective)
-In-vivo TDR, TBR and DBR
-The accuracy of SGM-101 to discriminate HGD/T1RC from LGD ex-vivo. A TDR of ≥1,5 is defined as true positive. A TDR of <1.5 is defined as false negative. The accuracy is defined as the percentage of patients that are true positive. Same analysis will be performed for TBR and DBR.
-The accuracy of SGM-101 to discriminate HGD/T1RC from LGD in-vivo. Accompanying endpoint is the percentage of true positives (fluorescent spot in vivo correlated to T1/HGD at pathology), false negatives (no fluorescent hotspot in vivo, T1/HGD component at pathology), false positives (fluorescent hotspot in-vivo, no T1/HGD at pathology) and true negatives (no fluorescent hotspot in vivo, no T1RC/HGD at pathology). Same analysis will be performed for TBR and DBR.
- The correlation between in-vivo TBR/TDR and Kudo level (SM1 vs SM2/3)
-The agreement of resection margins assessed by fluorescence and histopathology.
-The correlation between serum CEA expression to TDR, TBR and DBR
- The ratio of tissue CEA expression of T1/HGD divided by LGD, to TDR. The amount of CEA expression is determined by immunohistochemistry and quantified using the immunoreactive score (IRS)[28]. The ratio is calculated by dividing the IRS of T1RC/HGD by the IRS of LGD, after which this ratio is correlated to the TDR.
The same analysis will be performed for the TBR and DBR

E.5.2.1

Timepoint(s) of evaluation of this end point

During surgery in vivo pictures are made
After surgery ex vivo pictures are performed.
Subsequently the images and accompanying data can be analysed

Tijdens de operatie worden in vivo foto's gemaakt
Na de operatie worden ex vivo foto's gemaakt.
Vervolgens kunnen de beelden en de bijbehorende gegevens worden geanalyseerd

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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

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

Yes

E.8.1.7.1

Other trial design description

Het is een open gelabeld prospectief haalbaarheids- en doseringsonderzoek

It is an open labeled prospective feasibility and dose-finding study

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

Yes

E.8.2.3.1

Comparator description

andere doseringen

Other dosages

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

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

The trial ends after 20 patients were included, or:
It will be stopped in case of an unacceptable tolerability profile based on the nature, frequency, and intensity of observed AEs judged jointly by the principal investigator, SurgiMab and the independent investigator Dr. Liefers
Furthermore, if no fluorescent signal is seen for patients with a proven adenocarcinoma in the first 5 patients, the study will be stopped for futility.

De proef eindigt nadat 20 patiënten zijn geïncludeerd, of:
Het wordt gestopt in geval van een onaanvaardbaar verdraagbaarheidsprofiel op basis van de aard, frequentie en intensiteit van de waargenomen AE's, gezamenlijk beoordeeld door de hoofdonderzoeker, SurgiMab en de onafhankelijke onderzoeker dr. Liefers.
Bovendien zal de studie worden stopgezet wegens nutteloosheid indien bij de eerste 5 patiënten met een bewezen adenocarcinoom geen fluorescerend signaal wordt gezien.

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

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.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, standard of care

Volgens standaard zorg

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

2023-03-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-08-23

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

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