Clinical Trials Register

Summary
EudraCT Number:	2014-002352-12
Sponsor's Protocol Code Number:	OTL-038
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-06-23
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

2014-002352-12

A.3

Full title of the trial

A Single Ascending Dose, Open Label, Exploratory Study of OTL-038 for the Intra-operative Imaging of Folate Receptor Alpha Positive Ovarian, Renal Cell and Endometrial Cancer

A.3.1

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

Study to assess safety, tolerability and feasability of intra-operative imaging of cancer after OTL-038 injection in patients with ovarian, renal cell and endometrial cancer

A.3.2

Name or abbreviated title of the trial where available

Study for Intra-operative Imaging of Cancer using OTL-038

A.4.1

Sponsor's protocol code number

OTL-038

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	On Target Laboratories , LLC
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	On Target Laboratorties, LLC
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	Centre for Human Drug Research (CHDR)
B.5.2	Functional name of contact point	Research Director CVS & Metabolism
B.5.3	Address:
B.5.3.1	Street Address	Zernikedreef 10
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CL
B.5.3.4	Country	Netherlands
B.5.6	E-mail	kb@chdr.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	OTL-038
D.3.2	Product code	OTL-038
D.3.4	Pharmaceutical form	Solution for injection
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	n/a
D.3.9.1	CAS number	n/a
D.3.9.2	Current sponsor code	OTL-038
D.3.9.3	Other descriptive name	OTL-0038
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	0.2
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

Primary ovarian cancer planned for either primary debulking surgery or interval debulking surgery by laparotomy or planned for surgical staging by laparoscopy. Primary renal cell carcinoma planned for radical or partial nefrectomy. Primary high risk endometrial carcinoma planned for surgical staging or debulking surgery.

E.1.1.1

Medical condition in easily understood language

Ovarian, renal cell and endometrial cancer

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	PT
E.1.2	Classification code	10014733
E.1.2	Term	Endometrial cancer
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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10033131
E.1.2	Term	Ovarian carcinoma
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	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10038407
E.1.2	Term	Renal cell cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1. To assess the safety and tolerability of different doses of a single IV injection of OTL-038
2. To assess the efficacy of ascending doses of a single IV injection of OTL-038 in detecting ovarian, renal cell and endometrial cancer during surgery by :
a. Tumor to background ratio (TBR)
b. Concordance between fluorescent signal and tumor status of resected tissue
c. Detection of more FR-a+, cancer+ tumor lesions or resection margins with fluorescent light compared to usual visual/tactile conditions
3. To assess the surgeons’ opinion regarding the utility of OTL-038 IV injection and imaging system in debulking of cancer
4. To assess the pharmacokinetics of ascending doses of a single IV injection of OTL-038

E.2.2

Secondary objectives of the trial

1. To assess the efficacy of different imaging systems ex-vivo by
a. Back table TBR

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria ovarian cancer:
1. Known or high clinical suspicion of primary ovarian cancer planned for either primary debulking surgery or interval debulking surgery by laparotomy (18 patients)
2. Clinical suspicion of primary ovarian cancer planned for either laparoscopic staging procedure or laparoscopic procedure to determine optimal primary treatment (debulking surgery procedure vs neo-adjuvant chemotherapy) (15 patients)

Inclusion criteria renal cell cancer:
1. Known or high clinical suspicion of primary renal cell carcinoma planned for either primary radical nephrectomy by laparotomy or laparoscopy (3 patients) or partial nephrectomy by laparoscopy (15 patients)

Inclusion criteria endometrial cancer:
1. Known or high clinical suspicion of primary endometrial carcinoma planned for either primary staging or debulking surgery by laparotomy or laparoscopy (15 patients)

Inclusion criteria general:
1. 18 years of age and older
2. Normal or clinically acceptable medical history, physical examination (including vital signs), and laboratory tests at screening
3. Patients are clinically fit for surgery

E.4

Principal exclusion criteria

1. Any condition that in the opinion of the investigators could potentially jeopardize the health status of the patient
2. History of anaphylactic reactions or severe allergies
3. History of allergy to any of the components of OTL-038, including folic acid
4. Pregnancy, or positive pregnancy test
5. Clinically significant abnormalities in ECG and/or clinical laboratory test results
6. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
7. Impaired renal function defined as eGFR<50 ml/min/1.73m2
8. Impaired liver function defined as values greater than 3x the upper limit of normal (ULN) for ALT, AST, or total bilirubin.

E.5 End points

E.5.1

Primary end point(s)

Efficacy endpoints
1. TBR, defined as fluorescent signal of tumor tissue compared to fluorescence signal of tissue surrounding the tumor, at different doses;
2. Concordance between the pathology results with respect to the presence of cancer and the imaging assessment;
3. Number and location of FR-a+, cancer+ tumor lesions or resection margins identified under usual visual/tactile conditions, under both usual visual/tactile conditions and fluorescent light, and under fluorescent light only
4. Surgeons’ opinion regarding utility of IV OTL-038 injection and imaging system

Tolerability / safety endpoints
Treatment-emergent adverse events (TEAEs) using MedDRA from the time of administration throughout the study period, and changes in serum biochemistry, hematology, urinalysis, vital signs, ECG, injection site status, and physical examination findings.

Pharmacokinetic endpoints
Cmax, T½, AUC, Tmax, Clearance, urine excretion

E.5.1.1

Timepoint(s) of evaluation of this end point

Tolerability / safety endpoints
from predose up to infinity

Other endpoints
from predose up to 24 hours post dose

E.5.2

Secondary end point(s)

n/a

E.5.2.1

Timepoint(s) of evaluation of this end point

n/a

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

Yes

E.6.5

Efficacy

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)

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

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

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

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

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

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

2014-06-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-08-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-09-09

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