Clinical Trials Register

Summary
EudraCT Number:	2021-000591-10
Sponsor's Protocol Code Number:	CNIS793B12301
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:	2021-09-08
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

2021-000591-10

A.3

Full title of the trial

A randomized, double-blind, phase III study comparing NIS793 in combination with gemcitabine and nab-paclitaxel versus placebo combined with gemcitabine and nab-paclitaxel for first line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC)

Randomizované, dvojito zaslepené klinické skúšanie fázy III porovnávajúce NIS793 v kombinácii s gemcitabínom a nab-paklitaxelom verzus placebo kombinované s gemcitabínom a nab-paklitaxelom v prvej línii liečby metastatického duktálneho adenokarcinómu pankreasu (mPDAC)

A.3.1

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

Study of efficacy and safety of NIS793 in combination with standard of care (SOC) chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC)

Klinické skúšanie hodnotiace účinnosť a bezpečnosť NIS793 v kombinácii so štandardnou chemoterapiou v prvej línii liečby metastatického duktálneho adenokarcinómu pankreasu (mPDAC)

A.4.1

Sponsor's protocol code number

CNIS793B12301

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	Novartis Pharma 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	Novartis Pharma 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	Novartis Slovakia s.r.o.
B.5.2	Functional name of contact point	DRA information desk
B.5.3	Address:
B.5.3.1	Street Address	Žižkova 22/B
B.5.3.2	Town/ city	Bratislava
B.5.3.3	Post code	SK-811 02
B.5.3.4	Country	Slovakia
B.5.4	Telephone number	+421 2 50706116
B.5.5	Fax number	+421 2 50706100
B.5.6	E-mail	dra.slovakia@novartis.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.3.2	Product code	NIS793
D.3.4	Pharmaceutical form	Concentrate for solution for 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	not yet defined
D.3.9.2	Current sponsor code	NIS793
D.3.9.3	Other descriptive name	NIS793
D.3.9.4	EV Substance Code	SUB184323
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	100
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	Yes
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.2.1.2	Country which granted the Marketing Authorisation	European Union
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	nab-paclitaxel
D.3.4	Pharmaceutical form	Powder for dispersion for 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	Paclitaxel
D.3.9.1	CAS number	33069-62-4
D.3.9.3	Other descriptive name	PACLITAXEL ALBUMIN-BOUND
D.3.9.4	EV Substance Code	SUB127678
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	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.2.1.2	Country which granted the Marketing Authorisation	European Union
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	gemcitabine
D.3.4	Pharmaceutical form	Powder for solution for 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	GEMCITABINE
D.3.9.1	CAS number	95058-81-4
D.3.9.3	Other descriptive name	gemcitabine
D.3.9.4	EV Substance Code	SUB07892MIG
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	38
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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pancreatic ductal adenocarcinoma

E.1.1.1

Medical condition in easily understood language

Pancreatic 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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10033604
E.1.2	Term	Pancreatic 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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

safety run in: to confirm the recommended phase 3 dose (RP3D) of NIS793 in combination with gemcitabine and nab-paclitaxel
randomized part: to compare OS in participants with mPDAC treated as the first line treatment with the combination of NIS793, gemcitabine and nab-paclitaxel to the combination of placebo with gemcitabine and nab-paclitaxel

E.2.2

Secondary objectives of the trial

safety run in:
1. safety and tolerability of NIS793 in combination with SoC
2. PK of NIS793 in combination with SoC
3. preliminary anti-tumor activity of NIS793 in combination with SoC

randomized part:
1. efficacy (PFS, ORR, DCR; DOR, TTR) of NIS793 in combination with SoC versus placebo in combination with SoC
2. safety and tolerability in each treatment arm
3. explore PK of NIS793 in combination with gemcitabine and nabpaclitaxel
4. characterize the incidence of immunogenicity of NIS793 in
combination with gemcitabine/nab-paclitaxel

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants eligible must meet all of the following criteria:
1. signed ICF prior to study treatment
2. age >= 18 years at the time of ICF
3. histologically or cytologically confirmed mPDAC eligible for treatment in first line setting and not amenable for potentially curative surgery
4. presence of at least one measurable lesion assessed by CT and/or MRI according to RECIST 1.1
5. ECOG performance status 0-1
6. adequate organ function as defined by the following laboratory values:
- ANC >= 1.5 x 10*9 /L
- platelets >= 100 x 10*9/L
- hemoglobin >= 9g /dL
- calculated creatinine clearance >= 60 mL/min
- albumin >= 3 g/dL
- PT/INR and PTT <= 1.5 x ULN
- total bilirubin <= 1.5 X ULN
- AST and ALT <= 3.0 x ULN
7. WCBP must have negative pregnancy test during screening and before starting study treatment
8. able to adhere to study visit schedule and other protocol requirements
9. must have recovered from treatment-related toxicities of prior anticancer therapies to grade <= 1 (CTCAE v 5.0), except alopecia

E.4

Principal exclusion criteria

participants meeting any of the following criteria are not eligible for inclusion:
1. previous systemic anti-cancer treatment for mPDAC
2. pancreatic neuroendocrine (inslet) acinar or tumors
3. known status of MSI-H or MMR-deficient pancreatic cancer
4. presence of symptomatic CNS metastases, or CNS metastases that requires direct therapy or increasing doses of corticosteroids 2 weeks prior to study entry
5. known history of severe allergy or hypersensitivity to any of the study drug or their excipients
6. currently receiving any of the prohibited medications which cannot be discontinued within >= 7 days or 5 half-lifes, whichever is longer
7. not recovered from a major surgery or has a major surgery within 4 weeks prior to start of the study
8. radiation therapy or brain radiotherapy <= 4 weeks prior to study start
9. impaired cardiac function or clinically significant cardio-vascular disease, such as:
- congestive heart failure requiring treatment (NYHA grade >= 2), or clinically significant arrhythmia
- acute myocardial infarction, unstable angina pectoris, coronary stenting or bypass surgery < 3 months prior to study entry
- LVEF < 50%
- elevated cardiac enzymes (troponin I) > 2 x ULN
- cardiac valvulopathy >= grade 2
- uncontrolled hypertension
10. history of positive test for HIV infection
11. active or chronic HBV or HCV infections (patients with a history of
HCV infection must have been treated with confirmation of cure to be
eligible)
12. active untreated or uncontrolled systemic fungal, bacterial or viral infections
13. use of hematopoietic growth factors or transfusion support <= 2 weeks prior to start the study
14. conditions that are considered to have a high risk of clinically significant gastrointestinal track bleeding or any other condition associated with or history of significant bleeding
15. serious, non-healing wounds
16. pre-existing peripheral neuropathy > grade 1
17. concurrent malignancy other than disease under treatment
18. any significant medical condition, laboratory abnormality or psychiatric or social condition that would constitute unacceptable risk to the patients, contraindicate participation, limit patient's ability to comply with study requirements or compromise patient's compliance with the study protocol
19. pregnant or breast-feeding woman
20. WCBP, unless using highly effective method of contraception during and up to 90 days after the study drug treatment (NIS793)
21. currently receiving other anti-cancer therapy or received other investigational product within 30 days or 5 half-lives prior to study treatment, whichever is longer

E.5 End points

E.5.1

Primary end point(s)

safety run in: incidence of DLTs in the first cycle
randomized part: OS

E.5.1.1

Timepoint(s) of evaluation of this end point

safety run in: 4 weeks of treatment
randomized part: at participants' death

E.5.2

Secondary end point(s)

safety run in:
1. safety: incidence and severity of AEs
2. tolerability: dose interruptions, dose reductions, dose intensity
3. PK parameters for NIS793 in combination with SoC
4. PFS, ORR, DCR, DOR, TTR

randomized part:
1. PFS, ORR, DCR, DOR, TTR
2. incidence and severity of AEs and SAEs, dose interruptions, dose reductions
3. For participants with intense PK sampling enrolled in China, NIS793
serum concentrations over time and derived PK parameters (e.g. Cmax, AUC)
4. For participants without intensive PK sampling, PK parameters
including Cmax, Ctrough and Ctroughss for NIS793
5. Anti-drug antibodies (ADA) prevalence at baseline and ADA incidence on-treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

safety run in:
1-3. first 4 weeks of treatment
4. end of study

randomized part
at protocol defined timepoints (12 weeks)
end of study

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)

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Singapore

Switzerland

Taiwan

Australia

Brazil

Canada

China

Israel

Japan

Korea, Republic of

Russian Federation

United Kingdom

United States

Belgium

Czechia

Finland

France

Germany

Greece

Hungary

Italy

Netherlands

Norway

Slovakia

Spain

Sweden

Türkiye

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

Study will be considered complete when each participant has
completed at least 12 months of follow-up from randomization date,
died, withdrawn consent, or lost to follow-up, whichever occurs earliest
or, in the event of an early study termination. At which time, any study
participant continuing with standard of care chemotherapy
(gemcitabine + nab-paclitaxel) will be transitioned off the study and
LPLV will be achieved.

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:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

290

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

200

F.4.2.2

In the whole clinical trial

490

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)

All safety assessments (including pregnancy test for female participants of child bearing potential) should be completed as per Table 8-2a (post implementation of protocol amendment 3, Table 8-2b must be followed). All AEs and SAEs will be reported until the end of post-treatment safety follow-up.

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

2021-12-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-20

P. End of Trial
P.	End of Trial Status	Completed

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