Clinical Trials Register

Summary
EudraCT Number:	2017-005170-19
Sponsor's Protocol Code Number:	HP-CD-CL-2004
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-04-10
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

Sweden - MPA

A.2

EudraCT number

2017-005170-19

A.3

Full title of the trial

A Long-Term Follow-up Safety Study for Patients with Idiopathic Parkinson’s Disease (PD) Implanted with the DDS and/or Who Received Treatment in the Main Study and/or Extension Study

Långtidsuppföljningsstudie avseende säkerhet för patienter med idiopatisk Parkinsons sjukdom (PS) med en DDS inplanterad och/eller som har fått behandling i huvudstudien och/eller förlägningsstudien

A.3.1

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

A Long-Term Follow-up Safety Study for Patients with Parkinson’s Disease (PD) Implanted with the Drug Delivery System (DDS) and/or Who Received Treatment in the Main Study and/or Extension Study

A.3.2

Name or abbreviated title of the trial where available

Long-Term Follow-up Safety After DDS Implantation with/without CDNF Infusions

A.4.1

Sponsor's protocol code number

HP-CD-CL-2004

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	Renishaw Neuro Solutions Ltd.
B.1.3.4	Country	United Kingdom
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	Herantis Pharma Plc
B.4.2	Country	Finland
B.4.1	Name of organisation providing support	Renishaw Neuro Solutions Ltd.
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Renishaw Neuro Solutions Ltd.
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Wotton Road Charfield, Wotton-under-Edge
B.5.3.2	Town/ city	Gloucestershire
B.5.3.3	Post code	GL12 8JR
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441453 524395
B.5.6	E-mail	jim.baker@renishaw.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	Cerebral Dopamine Neurotrophic Factor
D.3.2	Product code	CDNF
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	Intracerebral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not Applicable
D.3.9.3	Other descriptive name	recombinant human Cerebral Dopamine Neurotrophic Factor
D.3.10	Strength
D.3.10.1	Concentration unit	µg/µl microgram(s)/microlitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
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	Yes
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

Idiopathic Parkinson's Disease

E.1.1.1

Medical condition in easily understood language

Parkinson's Disease

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

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	10013113
E.1.2	Term	Disease Parkinson's
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the long-term safety and tolerability of
– The implanted IMD, and,
– The previous administered bilateral intraputamenal IMP infusions

E.2.2

Secondary objectives of the trial

Evaluate the device:
• The patient’s skin healing after port removal
• The safety of the explantation procedures, when also subcutaneous and brainimplanted parts of the DDS are removed

Evaluate the long-term drug related effects:
• the severity of PD motor symptoms as measured by OFF-state UPDRS motor scores (part III)
• mobility as measured by OFF-state TUG test
• ON-state non-motor and motor function, motor complications, and ON- and OFF-state activities of daily living
• functional status by PD home diary
• health and daily activities as measured by PDQ-39 questionnaire
• treatment response on mental status as measured by CGI scale

Exploratory objectives:
To evaluate the drug related effects on
• the change in caudate and putamen dopamine transporter (DAT) availability after 7 months since last treatment infusion, using PET
imaging
• the daily activity measurement by Parkinson’s KinetiGraph

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients who completed Visit 4, implantation of the DDS, in the main study (HP-CD-CL-2002).
2. Patients that fulfil any of the following criteria:
a. Discontinued the main study (HP-CD-CL-2002) after Visit 4, or, the extension study (HP-CD-CL-2003), or,
b. Completed the main study (HP-CD-CL-2002) having received 6 doses of treatment, but did not continue in the extension study (HP-CD-CL-2003), or,
c. Patients that completed also the extension study, receiving a total of 12 doses of treatment (HP-CD-CL-2003).
3. Provision of informed consent. The patient is judged by the investigator to be alert and oriented to person, place, time and situation when giving the informed consent.

E.4

Principal exclusion criteria

None.

E.5 End points

E.5.1

Primary end point(s)

Device related
• Occurrence of adverse device effects (ADE), for either the whole system or the individual sub systems (guide tubes/catheters, subcutaneous components, port), evaluated separately for
o the explantation procedure (Week 55),
o the healing period (Weeks 55 to 57),
o the subsequent safety visits
during the entire study period outside of the explantation and healing period (Week 55 to Week 57), with serious adverse device effect (SADE), including long term pathological changes seen by MRI , neurological deficit (seizures), infection (local to components, in CNS), severe skin breakdown or necrosis requiring component removal and life threatening or major (requiring intervention) intracerebral haemorrhage up to 5 years since the initial surgical implantation of the DDS.

Drug related
• Change from study start (Week 49) until thirteen months after the last treatment infusion (Month 25) in adverse events (AEs), Electrocardiogram (ECGs), Beck Depression Inventory (BDI) score, questionnaire for impulsive-compulsive disorder in Parkinson’s disease rating scale (QUIP-RS), Montreal cognitive assessment (MoCA) score, physical examination, vital signs, clinical laboratory variables and anti-CDNF antibodies in serum.

E.5.1.1

Timepoint(s) of evaluation of this end point

Device related
• explantation procedure Week 55
• healing period Weeks 55 to 57
• subsequent safety visits during the entire study period up to 5 years

Drug related
• Change from study start (Week 49) until thirteen months after the last treatment infusion (Month 25)

E.5.2

Secondary end point(s)

Drug related
1. Change from baseline (Week -1), study start (Week 49) and after thirteen months of follow-up (Month 25) in severity of PD motor symptoms by UPDRS Part III motor scores.
2. Change from baseline (Week -1), study start (Week 49) and after thirteen months of follow-up (Month 25) in mobility by TUG test.
3. Change from baseline (Week -1), study start (Week 49) and after thirteen months of follow-up (Month 25) in severity of PD non-motor and motor symptoms by UPDRS Part I-IV total scores (Parts I, II and IV in ON-state; Part III in OFF-state).
4. Change from baseline (Week -1), study start (Week 49) and after thirteen months of follow-up (Month 25) in functional status by home diary score.
5. Change from baseline (Week -1), study start (Week 49) and after thirteen months of follow-up (Month 25) in health and daily activity by PDQ-39 questionnaire score.
6. Change from baseline (Week -1), study start (Week 49) and after thirteen months of follow-up (Month 25) in mental status as measured by CGI-I scale.

Exploratory Endpoints
Drug related (only for patients that have baseline DAT-PET and PKG TM data from HP-CD-CL-2002)
1. Change in caudate and putamen DAT availability from the previous DAT-PET image(s) in study HP-CD-CL-2002 (Week -2 and 22) or Study HP-CD-CL-2003 (Week47) and until seven months since the last treatment visit (Visit 33, Week 75) using PET imaging with [ 18 F]FE-PE2I to assess the integrity of the nigrostriatal system.
2. Change from inclusion (Week 49), after three months (Week 58) and until seven months since the last treatment visit (Week 71) in daily activity measurement by Parkinson’s KinetiGraph™ (PKG™) Data Logger.

E.5.2.1

Timepoint(s) of evaluation of this end point

Drug related
1. - 3. baseline (Week -1), study start (Week 49) and after thirteen months of follow-up (Month 25)
4. - 6. baseline (Week -1), study start (Week 49) and after thirteen months of follow-up (Month 25)

Exploratory Endpoints
Drug related
1. until seven months since the last treatment visit (Visit 33, Week 75)
2. inclusion (Week 49), after three months (Week 58) and until seven months since the last treatment visit (Week 71)

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

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

For patients who completed study HP-CD-CL-2002 and/or HP-CD-CL-2003, or who discont. in either study

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

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

Yes

E.8.2.3.1

Comparator description

different doses of the same product

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

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

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

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)

Yes

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)

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

2018-05-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-07-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-04-30

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