Clinical Trials Register

Summary
EudraCT Number:	2018-002734-20
Sponsor's Protocol Code Number:	R3918-PNH-1852
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-03-25
Trial results	View 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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2018-002734-20

A.3

Full title of the trial

An Open Label, Single Arm Study to Evaluate the Efficacy and Safety of REGN3918 in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Are Complement Inhibitor Naive or Have Not Recently Received Complement Inhibitor Therapy

Nyílt címkés, egykarú vizsgálat a REGN3918 hatásosságának és
biztonságosságának értékelésére olyan paroxysmalis nocturnalis
haemoglobinuriában (PNH) szenvedő betegeknél, akiket korábban még
nem kezeltek komplementgátlóval vagy a közelmúltban nem kaptak
komplementgátló terápiát

A.3.1

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

A trial with REGN3918 in patients Paroxysmal Nocturnal Hemoglobinuria (PNH) who have not been treated previously with a Complement Inhibitor or Have Not Recently Received Complement Inhibitor Therapy

A.4.1

Sponsor's protocol code number

R3918-PNH-1852

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	Regeneron Pharmaceuticals, Inc.
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	Regeneron Pharmaceuticals, Inc.
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	Regeneron Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	777 Old Saw Mill River Road
B.5.3.2	Town/ city	Tarrytown, NY
B.5.3.3	Post code	10591
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrials@regeneron.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	REGN3918
D.3.2	Product code	REGN3918
D.3.4	Pharmaceutical form	Lyophilisate for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	REGN3918
D.3.9.2	Current sponsor code	REGN3918
D.3.9.3	Other descriptive name	REGN3918
D.3.9.4	EV Substance Code	SUB184871
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	265
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.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.3.1	Product name	REGN3918
D.3.2	Product code	REGN3918
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 Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	REGN3918
D.3.9.2	Current sponsor code	REGN3918
D.3.9.3	Other descriptive name	REGN3918
D.3.9.4	EV Substance Code	SUB184871
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	200
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

Paroxysmal nocturnal hemoglobinuria

E.1.1.1

Medical condition in easily understood language

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the destruction of red blood cells.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10055629
E.1.2	Term	Paroxysmal nocturnal hemoglobinuria
E.1.2	System Organ Class	100000004857

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

The primary objective of the study is to demonstrate a reduction in intravascular hemolysis by REGN3918 over 26 weeks of treatment in patients with active PNH who are treatment naive to complement inhibitor therapy or have not recently received complement inhibitor therapy

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are:
•To evaluate the safety and tolerability of REGN3918.
•To evaluate the effect of REGN3918 on parameters of intravascular hemolysis
•To assess the concentrations of total REGN3918 in serum.
•To evaluate the incidence of treatment emergent anti drug antibodies to REGN3918.
•To evaluate the effect of REGN3918 on patient reported outcomes (PROs) measuring fatigue and health related quality of life

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

There are optional future biomedical research and pharmacogenomic analysis sub-studies . Subjects will be required to sign separate sub-study ICFs before collection of samples. There is no separate protocol.
The purpose of the genomic analyses is to identify genomic associations with clinical or biomarker response, other clinical outcome measures and possible AEs. In addition, associations between genomic variants and prognosis or progression of as well as other diseases may also be studied.
In addition, PROs such as fatigue or quality of life in a subset of patients at participating sites will be assessed (ie, sub study).
There will not be separate sub-study protocols.

E.3

Principal inclusion criteria

• Male or female ≥ 18 years of age or legal age of majority at screening, whichever is greater
•Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) confirmed by high sensitivity flow cytometry
•Active disease, as defined by the presence of 1 or more PNH related signs or symptoms or history of red blood cell (RBC) transfusion due to PNH within 3 months of screening.
•Lactate dehydrogenase (LDH) level ≥ 2 × upper limit of normal (ULN) at screening visit.
• PNH granulocytes (denoted as polymorphonuclear [PMN]) >10% at screening visit.

E.4

Principal exclusion criteria

•Prior treatment with a complement inhibitor either within 6 months prior to screening visit or at any time where the patient was refractory to complement inhibitor therapy, in the opinion of the investigator (with the exception of eculizumab refractory patients due to the C5 variant R885H/C)

E.5 End points

E.5.1

Primary end point(s)

The co primary endpoints are:
•The proportion of patients achieving adequate control of their intravascular hemolysis, defined as LDH ≤ 1.5 x ULN at every scheduled time point between week 4 and week 26, inclusive
•The proportion of patients achieving transfusion avoidance defined as no post baseline transfusion of RBCs per protocol over 26 weeks

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks

E.5.2

Secondary end point(s)

The secondary endpoints include:
•The rate of breakthrough hemolysis over 26 weeks, defined as the measurement of LDH ≥ 2 x ULN concomitant with associated signs or symptoms at any time subsequent to an initial achievement of disease control (ie, LDH ≤ 1.5 x ULN)
•The proportion of patients achieving normalization of their intravascular hemolysis, defined as LDH ≤ 1.0 x ULN at every scheduled time point between week 4 through week 26, inclusive
•Time to first LDH ≤ 1.5 x ULN
•Percentage of days with LDH ≤ 1.5 x ULN between week 4 and week 26, inclusive.
•Change and percent change in LDH levels from baseline to week 26

E.5.2.1

Timepoint(s) of evaluation of this end point

26 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

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

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

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

Canada

Germany

Hong Kong

Hungary

Italy

Korea, Democratic People's Republic of

Malaysia

Netherlands

Poland

Romania

Singapore

South Africa

Taiwan

United Kingdom

United States

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

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:

F.1.3

Elderly (>=65 years)

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)

Patients will be offered the opportunity to enter a separate open label extension trial with REGN3918

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

2019-05-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-04-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-06-10

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