Clinical Trials Register

Summary
EudraCT Number:	2013-000321-31
Sponsor's Protocol Code Number:	rhLAMAN-09
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-02-21
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2013-000321-31

A.3

Full title of the trial

A multi-center, un-controlled, open-labeled trial of the long-term safety of Velmanase Alfa aftercare
treatment of subjects with alpha-Mannosidosis whom previously participated in Velmanase Alfa - trials

A.3.1

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

A long-term safety trial of repeated Velmanase Alfa treatment of subjects with Alpha-Mannosidosis

A.3.2

Name or abbreviated title of the trial where available

Phase IIIb

A.4.1

Sponsor's protocol code number

rhLAMAN-09

A.5.4

Other Identifiers

Name:

EudraCT

Number:

2013-000321-31

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	Chiesi Farmaceutici S.p.A.
B.1.3.4	Country	Italy
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	Chiesi Farmaceutici S.p.A
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Chiesi Farmaceutici S.p.A
B.5.2	Functional name of contact point	Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Via Palermo
B.5.3.2	Town/ city	Parma
B.5.3.3	Post code	43122
B.5.3.4	Country	Italy
B.5.4	Telephone number	003905211689176
B.5.6	E-mail	clinicaltrials_info@chiesi.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/260
D.3 Description of the IMP
D.3.1	Product name	Velmanase Alfa
D.3.2	Product code	rhLAMAN
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	velmanase alfa
D.3.9.1	CAS number	1492823-75-2
D.3.9.2	Current sponsor code	rhLAMAN
D.3.9.3	Other descriptive name	recombinant human alpha-mannosidase
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	2
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.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

Treatement of Alpha-Mannosidosis

E.1.1.1

Medical condition in easily understood language

Treatement of Alpha-Mannosidosis

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10032658
E.1.2	Term	Other specified disorders of carbohydrate transport and metabolism
E.1.2	System Organ Class	100000004850

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 overall objective of this trial is to provide aftercare treatment with Velmanase- Alfa and to evaluate the safety and efficacy of repeated Velmanase- Alfa i.v. treatment of subjects with alpha-Mannosidosis whom previously participated in Velmanase- Alfa -trial. This protocol only concern subjects, where compassionate use program was not accepted (OR NO PHYSICIAN COULD BE IDENTIFIED)
Efficacy will be evaluated once yearly to follow the subject’s progress in clinical parameters and at one additional comprehensive evaluation visit (2500) to evaluate additional efficacy parameters.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The subject must have participated in previous Velmanase- Alfa -trials: phase 2b: 2011-004355-40 or phase 3: 2012-000979-17
2. Subject or subjects legally authorized guardian(s) must provide signed, informed consent prior to performing any trial-related activities
3. The subject and his/her guardian(s) must have the ability to comply with the protocol

E.4

Principal exclusion criteria

1. Presence of known clinically significant cardiovascular, hepatic, pulmonary, or renal disease or other medical conditions that, in the opinion of the Investigator, would preclude participation in the trial
2. Any other medical condition or serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, would preclude participation in the trial
3. Pregnancy: Pregnant woman is excluded. Before start of the treatment the investigators will for women of childbearing potential perform a pregnancy test and decide whether or not there is a need for contraception
4. Psychosis; any psychotic disease, also in remission, is an exclusion criteria
5. Planned major surgery that, in the opinion of the Investigator, would preclude participation in the trial

E.5 End points

E.5.1

Primary end point(s)

All endpoints are evaluated as change from baseline (pre-treatment in the subject’s original Velmanase- Alfa trial).
Safety Endpoints:
• Adverse events (AEs)
• Vital signs and change in physical examination
• Development of Velmanase- Alfa antibodies and neutralizing/inhibitory antibodies

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety will be assessed at every visit.
Development of antibodies are measured every 12th week

E.5.2

Secondary end point(s)

All endpoints are evaluated as change from baseline (pre-treatment in the subject’s original Velmanase- Alfa trial).
The Efficacy endpoints of the trial are evaluation of:
o Oligosaccharides in serum (visit 2500 only)
o Motor proficiency (BOT-2) (visit 2500 only)
o Three minute stair climb test (3MSCT)
o Leiter R
o Forced Vital Capacity (FVC)
o Six minute walk test (6MWT)
o Pure tone Audiometry
o Questionnaires
CNS parameters (visit 2500 only):
o Assessment of mannose-rich oligosaccharides in brain tissue as measured by MRS visual score (for patients who previously participated in rhLAMAN-02), MRI diffusion coefficient in white matter, gray matter and centrum semi oval
o Cerebrospinal fluid neuro-degeneration biomarker (Tau, NFL, GFAp)
o Oligosaccharides in CSF
Other laboratory parameters (visit 2500 only):
o Plasma PK profile
o Oligosaccharides in 24-h urine collection
o Measurement of in vivo biological activity

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy will be assessed yearly, counted from the latest evaluation in the subject's previous Velmanase- Alfa trial, and at one additional comprehensive evaluation visit (2500) to evaluate additional efficacy parameters.

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

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.8.3

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

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

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)

Yes

F.1.2.1

Number of subjects for this age range:

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Due to the disease related mental retardation the subjects are under gardianship of the parents

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)

When the trial is completed, given no safety concerns have arisen, all subjects will be offered to receive Velmanase- Alfa as post study therapy in the home country. This will last until the product is available on the market or until the sponsor decides to terminate the project. If the project is terminated, Chiesi has no further obligation to provide the study drug, even for post study therapy

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Wieslab AB (former BioMonitor)
G.4.3.4	Network Country	Sweden

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-06-27

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	Completed
P.	Date of the global end of the trial	2022-09-30

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