Clinical Trials Register

Summary
EudraCT Number:	2019-004016-58
Sponsor's Protocol Code Number:	WPD-201P
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-06-28
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2019-004016-58

A.3

Full title of the trial

A Phase 1, Multicenter, Open-label, Dose Escalation
Study of the Safety and Pharmacokinetics of
Intravenously Infused Berubicin® in Pediatric Patients
with Progressive, Refractory, or Recurrent High Grade
Gliomas

A.3.1

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

A Phase 1, Open-label , Dose Escalation
Study of Berubicin® in Pediatric Patients
with Progressive, Refractory, or Recurrent High Grade
Gliomas

A.4.1

Sponsor's protocol code number

WPD-201P

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	WPD Pharmaceuticals Sp. z o.o.
B.1.3.4	Country	Poland
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	WPD Pharmaceuticals Sp. z o.o.
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	WPD Pharmaceuticals Sp. z o.o.
B.5.2	Functional name of contact point	WPD Pharmaceuticals Sp. z o.o.
B.5.3	Address:
B.5.3.1	Street Address	Żwirki i Wigury 101
B.5.3.2	Town/ city	Warsaw
B.5.3.3	Post code	02-089
B.5.3.4	Country	Poland
B.5.6	E-mail	wpd-201@wpdpharmaceuticals.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	Berubicin
D.3.2	Product code	WP 744
D.3.4	Pharmaceutical form	Lyophilisate and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Nasal use Vaginal use In vitro use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Berubicin hydrochloride
D.3.9.1	CAS number	293736-67-1
D.3.9.2	Current sponsor code	WP 744
D.3.9.3	Other descriptive name	Berubicin hydrochloride
D.3.10	Strength
D.3.10.1	Concentration unit	mg/l milligram(s)/litre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
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

High Grade Gliomas

E.1.1.1

Medical condition in easily understood language

High Grade Gliomas

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

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

Dose Escalation Cohorts: To estimate the maximum tolerated dose
(MTD) and/or the recommended Phase 2 dose (RP2D) of single-agent
Berubicin administered after at least 1 prior line of therapy in pediatric
patients with progressive, refractory, or recurrent HGG.
• Expansion Cohort: To evaluate the safety of Berubicin administered at
the MTD or RP2D to pediatric patients with progressive, refractory, or
recurrent HGG who have completed at least 1 prior line of therapy.

E.2.2

Secondary objectives of the trial

-To define and describe the toxicities associated with single-agent
Berubicin administered after at least 1 prior line of therapy to pediatric patients with progressive, refractory, or recurrent HGG.
- To characterize the PK of Berubicin and its metabolite, Berubicinol, in
a pediatric population.
- To estimate the incidence and duration of objective response (as
described in Efficacy Outcome Measures) in pediatric patients with
progressive, refractory, or recurrent HGG administered Berubicin after
at least 1 prior line of therapy.
- To estimate the progression-free survival (PFS) and OS in paediatric
patients with progressive, refractory, or recurrent HGG administered
Berubicin after at least 1 prior line of therapy.
-To explore the effects of Berubicin on patient-reported health-related
quality of life outcome and neurocognitive functioning using the Paediatric
Quality of Life Inventory (PedsQL™) brain tumor module on patients

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Written informed consent of the patient’s LAR, and assent when
appropriate based on the patient’s age and institutional guidelines, prior
to any study-related procedure.
2. Patients must have progressive, refractory, or recurrent HGG (WHO
Grade III or IV).
3. Age ≥2 to <18 years at the tiem of the first Berubicin dose.
4. Performance status score ≥50 (Lansky for research patients aged
≤16 years and Karnofsky for patients ˃16 years). Patients who are
unable to walk because of paralysis but who are up in a wheelchair will
be considered ambulatory for the purpose of assessing the performance
score.
5. Patients must have completed at least 1 line of prior therapy.
6. Before the projected start of scheduled study treatment, the following
time periods must have elapsed:
a. 5 half-lives from any investigational agent.
b. 4 weeks from cytotoxic therapy (except 23 days from
temozolomide and 6 weeks from nitrosoureas).
c. 6 weeks from antibody therapies.
d. 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor
therapies.
e. Patients who have received radiation therapy must be ≥6 weeks
post the completion of local palliative radiation therapy (reirradiation
for progressive disease or upfront radiation therapy at
initial diagnosis).
7. Adequate organ function defined as:
a. Bone marrow:i. Peripheral absolute neutrophil count ≥1000/mm3
ii. Hemoglobin ≥8 g/dL (may have received packed red blood cell
transfusion)
iii. Platelet count ≥100,000/mm3 (transfusion-independent, defined
as not receiving platelet transfusions for at least 7 days prior to
enrollment)
b. Renal function:
i. Creatinine clearance or radioisotope glomerular filtration rate
≥70 mL/min/1.73 m2 or normal serum creatinine based on age
as shown below:
 Age <5 years: 0.8 mg/dL maximum
 Age ≥5 to <10 years: 1.0 mg/dL maximum
 Age ≥10 to <15 years: 1.2 mg/dL maximum
 Age ≥15 years: 1.5 mg/dL maximum
c. Hepatic function:
i. Total bilirubin (sum of conjugated + unconjugated) ≤1.5 × the
upper limit of normal (ULN) for the institution
ii. Alanine aminotransferase ≤3 × ULN for the institution
iii. Serum albumin ≥2 g/dLd. Neurologic function:
i. Patients with seizure disorder may be enrolled if the seizure
disorder is well controlled, as determined by the investigator.
e. Cardiac function (left ventricular ejection fraction [LVEF]):
i. Fractional shortening ≥27% or LVEF ≥50% by echocardiogram
or multigated radionuclide study (MUGA)
8. All adverse events (AEs) Grade >1 related to prior therapies
(chemotherapy, radiation therapy, and/or surgery) must be resolved to
Grade 1 or baseline level, except for alopecia and sensory neuropathy
Grade ≤2 or other Grade ≤2 AEs not constituting a safety risk based on
the investigator's judgment.
9.For postpubertal patients: Female patients must agree to use highly
effective contraception during the period of the study and for at least
90 days after completion of treatment. Male patients must be
surgically sterile or must agree to use highly effective contraception
during the period of the study and for at least 90 days after completion
of treatment. Details are provided in the full protocol.
10. Female patients of childbearing potential aged 10 years or older must
have a negative serum or urine pregnancy test.
11. MRI of the brain and entire spine (including all sites of disease), within
10 days prior to start of study drug.
12. Corticosteroid dose must be stable or decreasing for at least 5 days
prior to the baseline MRI scan.

E.4

Principal exclusion criteria

1. Evidence of diffuse leptomeningeal disease or evidence of
cerebrospinal fluid (CSF) dissemination.
2. Known additional malignancy that is progressing or has required active
treatment within 3 years of start of study drug.
3. History of allergic reactions attributed to compounds of similar
chemical or biologic composition to Berubicin or its excipients.
4. Patients with any clinically significant, unrelated systemic illness (eg,
significant pulmonary, hepatic [including Gilbert’s syndrome], or other
organ dysfunction) or psychiatric illness/social situations that would
compromise the patient’s ability to tolerate the study drug or study
procedures or would likely interfere with the study procedures or
results.
5. Any known clinically significant active bacterial, fungal, or viral
infection including hepatitis B or hepatitis C, or any underlying disease
in the recent past that could compromise enrollment and the safety of
the patient.
6. Patient with a history of clinically significant, uncontrolled heart
disease and/or repolarization abnormalities as documented by a
standard 12-lead electrocardiogram (ECG).
7. Known history of cardiac arrhythmias including atrial fibrillation,
tachyarrhythmias, or bradycardia, unless arrhythmia is controlled and
after a cardiology consultation has cleared the patient to receive
Berubicin. Patients receiving therapeutic agents known to prolong QTinterval will be excluded; however, the use of ondansetron is permitted.
Patients with a history of congestive heart failure, myocardial
infarction, or stroke in the last 3 months will be excluded.
8. Congenital long QT syndrome or QTc >460 ms.
9. Patients receiving any other anticancer or investigational drug therapy.
10. Prior treatment with bevacizumab.
11. Current or planned participation in a study of another investigational
agent or using an investigational device.
12. Requirement for cytochrome P450 3A4 (CYP3A4)-inducing or
inhibiting agents, with the exception of corticosteroids.
Patients unable to return for follow-up visits or undergo follow-up
procedures required to assess toxicity of therapy.

E.5 End points

E.5.1

Primary end point(s)

• Dose Escalation Cohorts: MTD and/or RP2D of Berubicin in pediatric
patients with progressive, refractory, or recurrent HGG after at least
1 prior line of therapy.
• Expansion Cohort: Incidence of AEs at least possibly associated with
Berubicin when administered to pediatric patients with progressive,
refractory, or recurrent HGG after at least 1 prior line of therapy.

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary Endpoint Dose Escalation: MTD/RP2D will be assessed 21 days after last patient in a given cohort receives the 1st IMP dose
Primary Endpoint Dose Expansion: Incidence of AEs will be assessed at the end of the study (time point for AE reporting is 30 days after last dose for a given patient but AEs can be still reported thereafter if considered related to the IMP)

E.5.2

Secondary end point(s)

Secondary
Endpoint(s):
• Standard PK parameters for Berubicin and its metabolite, Berubicinol,
as derived from noncompartmental analysis of plasma drug
concentration-time data
• Objective response rate (ORR) (CR or PR to Berubicin within 6
months)
• Duration of response (DoR)
• Proportion of patients achieving CR within 6 months
• Proportion of patients achieving PR within 6 months
• Best overall response within 6 months
• PFS at 6 months
• OS at 6 months
• OS at end of the study
Exploratory
Endpoint(s):
• PedsQL brain tumor module scores

E.5.2.1

Timepoint(s) of evaluation of this end point

PK parameters will be evaluated at the same time points as MTD + at the end of the trial.
Efficacy parameters (all response parameters) and OS will be evaluated at the End of the trial.

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

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)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

First in Children

E.7.2

Therapeutic exploratory (Phase II)

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

Yes

E.8.1.7.1

Other trial design description

Dose escalation

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

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

tbc with WPD

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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)

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

2021-09-13

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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