Clinical Trials Register

Summary
EudraCT Number:	2019-004375-40
Sponsor's Protocol Code Number:	NGAM-12
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2020-03-09
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2019-004375-40

A.3

Full title of the trial

Double-blind, Randomized, Placebo-controlled, Prospective Phase III Study Evaluating Efficacy and Safety of Panzyga in Primary Infection Prophylaxis in Patients with Chronic Lymphocytic Leukemia (“PRO-SID” study)

Kettős vak, randomizált, placebo-kontrollos, prospektív, III. fázisú vizsgálat a Panzyga hatásosságának és biztonságosságának értékelésére primer fertőzés profilaxisban, krónikus limfocitás leukémiában szenvedő betegeknél („PRO-SID” vizsgálat)

A.3.2

Name or abbreviated title of the trial where available

PRO-SID

A.4.1

Sponsor's protocol code number

NGAM-12

A.5.4

Other Identifiers

Name:

IND Number

Number:

19414

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	Octapharma Pharmazeutika Produktionsges.m.b.H.
B.1.3.4	Country	Austria
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	Octapharma Pharmazeutika Produktionsges.m.b.H.
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Octapharma Pharmazeutika Produktionsges.m.b.H.
B.5.2	Functional name of contact point	Global Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Oberlaaer Str. 235
B.5.3.2	Town/ city	Vienna
B.5.3.3	Post code	1100
B.5.3.4	Country	Austria
B.5.4	Telephone number	+43(1)61032 1796
B.5.5	Fax number	+43(1)61032 1796
B.5.6	E-mail	AT1ClinicalDepartment@octapharma.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	Panzyga
D.2.1.1.2	Name of the Marketing Authorisation holder	Octapharma
D.2.1.2	Country which granted the Marketing Authorisation	Austria
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	Panzyga
D.3.4	Pharmaceutical form	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	Immunoglobulin G
D.3.9.1	CAS number	308067-58-5
D.3.9.2	Current sponsor code	N/A
D.3.9.3	Other descriptive name	HUMAN NORMAL IMMUNOGLOBULIN (IV)
D.3.9.4	EV Substance Code	SUB12041MIG
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)	Yes
D.3.11.7	Plasma derived medicinal product	Yes
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

Primary infection prophylaxis in patients with chronic lymphocytic leukemia (CLL) and secondary hypogammaglobulinemia

E.1.1.1

Medical condition in easily understood language

Prophylaxis to prevent infection in patients with a type of cancer that starts in bone marrow and then go into the blood

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	10008976
E.1.2	Term	Chronic lymphocytic leukemia
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

The primary objective of this study is to demonstrate the benefit of Panzyga administration compared with placebo as primary infection prophylaxis in CLL patients with secondary immunodeficiency (SID) undergoing CLL antineoplastic therapy.

E.2.2

Secondary objectives of the trial

The secondary objectives of this study are to compare the following aspects in CLL patients with SID treated with and without primary Panzyga prophylaxis:
• Overall infection rate
• Frequency of prophylaxis with anti-infectives (antibacterials and antivirals)
• Duration of prophylaxis with anti-infectives (antibacterials and antivirals)

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

Pharmacokinetic (PK) Sub-study:
Pharmacokinetic parameters will be determined in a subgroup of patients. Blood samples for the PK profiles of total IgG will be taken.
The following parameters will be assessed for patients treated with Panzyga.
• Half-life (T1/2)
• Area under the curve (AUC0-t; AUC0-infinity)
• Volume of distribution (Vd)
• Concentration maximum (Cmax; Tmax)
• Clearance (Cl)
For patients treated with Placebo, no PK parameters will be estimated, as the underlying assumptions for exponential modelling are not fulfilled.

E.3

Principal inclusion criteria

1. Treatment-naïve or relapsed/refractory CLL patients undergoing CLL antineoplastic treatment. Diagnosis of B-cell CLL established according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria and documented within medical records.
2. Hypogammaglobulinemia (IgG levels <5 g/L) as confirmed by the Central Laboratory.
3. ≥18 years of age.
4. Voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted.

E.4

Principal exclusion criteria

1. IgG treatment within 3 months prior to Screening.
2. Antibiotic prophylaxis and/or treatment within 7 days prior to current CLL treatment start (with the exception of trimethoprim-sulfamethoxazole [TMP/SMX], diaminodiphenyl sulfone [dapsone] and pentamidine inhalation).
3. Current major infection or >1 major infection in the previous 6 months before Baseline.
4. History of anaphylaxis or severe systemic response to immunoglobulin, blood or plasma-derived products or any Panzyga component.
5. History of a non-CLL malignancy with life-expectancy of less than two years.
6. Severe liver disease, with signs of ascites and/or hepatic encephalopathy.
7. Severe kidney disease (as defined by estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2).
8. Body weight >140 kg.
9. Eastern Cooperative Oncology Group (ECOG) performance score of >2 (Appendix 1).
10. Female patients of childbearing potential unwilling to use a protocol-required method of contraception from the Screening Visit throughout the study treatment period and for 30 days following the last dose of study drug.
11. Human immunodeficiency virus (HIV) infection at Screening (defined for the study as positive HIV antibody test).
12. Patients found to be chronic carriers of hepatitis B virus (HBV), defined by positive surface antigen (HBsAg), positive Hepatitis B core antibodies (HBcAb) and/or low HBV titers, who will not receive targeted antiviral therapy while undergoing CLL therapy, and patients with active HBV, defined as high HBV titers.
13. Uncontrolled hepatitis C infection at Screening (defined for the study as positive hepatitis virus C [HCV] polymerase chain reaction [PCR]).
14. Pregnant and lactating women.
15. Subjects with a history of thromboembolic events (TEE) such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease (Fontaine IV) within 6 months before Baseline.
16. Planned or ongoing immunosuppressive treatment (other than for CLL or corticosteroids) or other forbidden medication during the entire study duration after study enrollment.
17. Participation in another interventional clinical trial that is either blinded or involves an investigational (not approved) product within 3 months before Baseline or during the course of the clinical study. Participation in observational clinical trials or open-label trials involving an approved product may be permitted after consultation with the medical monitor.
18. Known IgA deficiency with antibodies to IgA (as part of the patient´s medical history).
19. Known blood hyperviscosity, or other hypercoagulable states.
20. Patients unable or unwilling to understand or comply with the study protocol.

E.5 End points

E.5.1

Primary end point(s)

Since the study objective is to show the benefit of Panzyga administration as primary infection prophylaxis, the primary endpoint is not the major infection rate but occurrence of at least one major infection in CLL patients with or without primary infection prophylaxis with Panzyga. Therefore, although patients will stay in the study regardless of the number of major infections, each patient will be counted only once for the primary endpoint calculation.
Major infection for this trial is defined as:
• Bacterial and/or viral infections resulting in death. Confirmed cases of COVID-19 are excluded.
• Bacterial and/or viral infections, which are microbiologically documented (MDI) or clinically documented (CDI) requiring treatment with anti-infectives; upper respiratory tract infections, bronchitis, lower urinary tract infections, bacterial skin infections and stomatitis (MDI or CDI) are considered major only if they require treatment with anti-infectives AND hospitalization or hospitalization prolongation. Confirmed cases of COVID-19 are excluded.
• FUO requiring hospitalization or hospitalization prolongation

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoint of major infection.

E.5.2

Secondary end point(s)

• Overall infection rate: infection rate for all infections.
• Frequency of prophylaxis with anti-infectives (antibacterials and antivirals).
• Duration of prophylaxis with anti-infectives (antibacterials and antivirals).

E.5.2.1

Timepoint(s) of evaluation of this end point

• Infections throughout the study
• anti-infectives frequency throughout the study
• duration of prophylaxis throughout the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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

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

Russian Federation

United States

Denmark

Germany

Hungary

Italy

Poland

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

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:

225

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

225

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

180

F.4.2.2

In the whole clinical trial

450

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

2020-09-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-08-25

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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