Clinical Trials Register

Summary
EudraCT Number:	2018-001703-37
Sponsor's Protocol Code Number:	D-FR-52120-244
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-08-02
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

UK - MHRA

A.2

EudraCT number

2018-001703-37

A.3

Full title of the trial

A double-blind, randomised, placebo controlled, proof-of-concept study in subjects with abdominal or thoracic chronic scar pain to assess the analgesic properties of intradermal doses of Dysport®

A.3.1

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

Dysport in Post-Surgical Neuralgia (RESPITE)

A.3.2

Name or abbreviated title of the trial where available

Dysport in Post-Surgical Neuralgia (RESPITE)

A.4.1

Sponsor's protocol code number

D-FR-52120-244

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	Ipsen Innovation SAS
B.1.3.4	Country	France
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	Ipsen Innovation SAS
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	St Pancras Clinical Research
B.5.2	Functional name of contact point	Dr Stuart Ratcliffe
B.5.3	Address:
B.5.3.1	Street Address	285-287 Gray's Inn Road
B.5.3.2	Town/ city	London
B.5.3.3	Post code	WC1X 8QD
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02038651142
B.5.5	Fax number	02078377707
B.5.6	E-mail	stuartratcliffe@stpancrasclinical.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	Dysport
D.2.1.1.2	Name of the Marketing Authorisation holder	IPSEN Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Dysport
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	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Clostridium botulinum type A toxin-haemagglutin complex
D.3.9.1	CAS number	953397-35-8
D.3.9.3	Other descriptive name	Dysport
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	equal
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Lyophilisate for solution for injection
D.8.4	Route of administration of the placebo	Intradermal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Post-Surgical neuralgia

E.1.1.1

Medical condition in easily understood language

Chronic scar-related pain after surgery

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10054095
E.1.2	Term	Neuropathic pain
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

The primary objective is to describe the pharmacodynamic analgesic profile (time of onset of meaningful analgesic effect, peak-effect, time to peak-effect, duration of effect) of intradermal doses of Dysport in subjects with abdominal or thoracic chronic scar pain.

E.2.2

Secondary objectives of the trial

The secondary objectives are to compare the efficacy of intradermal doses of Dysport to placebo, and to assess the safety and tolerability of a range of intradermal doses of Dysport.

In addition, exploratory objectives are to explore improvement of quality of life (QoL) using SF-36 questionnaire, and assess the concomitant use of rescue medication (analgesia).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

In order to be considered eligible for enrolment in the study, subjects must fulfil all of the following criteria:
1) Male and female subjects aged between 18 and 80 years inclusive at the time of giving informed consent.
2) Subjects suffering from an area of chronic pain post-abdominal or thoracic surgery, chronic abdominal or thoracic scar pain
3) Longitudinal axis of the pain area of 10 cm long maximum (as mapped upon screening).
4) Subjects with moderate to severe pain, i.e. spontaneous NRS score of 4-8 stable for the previous month before screening.
5) Stable use of analgesics (or any medication impacting pain perception) during the month before screening and expected to be stable for the study duration.
6) Time from surgery which caused the painful scar more than six months and less than five years at screening.
7) No other distracting pain either chronic or acute.
8) Female subjects of childbearing potential must have a negative urine pregnancy test result and be willing to use reliable contraceptive measures throughout study participation. Reliable forms of contraception include but are not limited to hormonal contraceptives (e.g. oral, patch, injection), double-barrier (e.g. male condom plus spermicide, or female diaphragm plus spermicide), intrauterine device, male partner has had a vasectomy, total abstinence from intercourse with male partners (periodic abstinence is not acceptable). Female subjects meeting any of the following criteria are not considered to be of childbearing potential: postmenopausal (≥ 47 years of age and amenorrhoeic for at least 12 consecutive months), have been sterilised surgically (e.g. bilateral tubal ligation), have had a hysterectomy, have had a bilateral oophorectomy.

E.4

Principal exclusion criteria

Subjects who meet any of the following criteria will not be considered eligible for enrolment in the study.
1) Previous treatment with BTX (any serotype) during the past six months before screening.
2) History of hypersensitivity to any of the components of the Dysport formulation (which includes human serum albumin and lactose) or allergy to cow's milk protein.
3) Known hypersensitivity to lidocaine or other anaesthetics of the amide type, known hypersensitivity to hydroxybenzoates, complete heart block, hypovolaemia.
4) Any medical condition that may put the subject at risk with exposure to BTX, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disease that might interfere with neuromuscular function.
5) Neuroma in the scar pain area, diagnosed per ultrasound.
6) Use of agents that could interfere with neuromuscular transmission, including calcium channel blockers, penicillamine, aminoglycosides, lincosamides, polymixins, magnesium sulphate, anticholinesterases, succinylcholine and quinidine.
7) Need of any prohibited medication.
8) Any abnormal laboratory value, physical examination, vital signs, or electrocardiogram (ECG) that, in the opinion of the investigator, is clinically significant and that would compromise the safety of the subject in the study.
9) Positive for hepatitis B antigen or hepatitis C virus ribonucleic acid, positive results for human immunodeficiency virus, or who receives diagnosis for acquired immunodeficiency syndrome.
10) Positive urine screen for drugs of abuse (except for cotinine and unless explained by the investigator for therapeutic use of medication) or any history of drug or alcohol abuse, misuse, physical or psychological dependence, mood changes, sleep disturbance and functional capacity which have an impact on pain perception.
11) Significant neurological or psychiatric disorders including mental instability (unrelated to the pain) that could interfere with pain assessments; other pre-existing pain syndromes, acute or chronic, that might impair the assessment of the scar pain.
12) Any medical history of significance and/or inadequately controlled such as cardiovascular (e.g. uncontrolled high blood pressure, high risk of cardiovascular events, severe heart failure), pulmonary (e.g. uncontrolled asthma or emphysema), heamatologic, (e.g. coagulopathy/bleeding disorders), neurological (e.g. swallowing problems, blurred or double vision, trouble saying words clearly (dysarthria), hoarseness or change or loss of voice (dysphonia)), liver disease (e.g. severe hepatic impairment), kidney disease (e.g. impaired renal function in subjects taking diuretics, angiotensin converting enzyme (ACE)-inhibitors, or angiotensin II antagonists), endocrine, immunologic, dermatologic painful conditions or any other conditions that may compromise in the opinion of the investigator the ability of the subject to participate in the study.
13) If in the investigator’s opinion there are any factors that may confound the analysis of the study regarding efficacy and safety (e.g. an NRS > 9).
14) The subject’s primary care physician has provided evidence which can be used to confirm that within the last 12 months of dosing that there is nothing in their medical history that would preclude their enrolment into a clinical study.
15) Previous randomisation in this study.
16) Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days before screening.
17) Subjects who are incapable of complying with the protocol in the judgment of the investigator.

E.5 End points

E.5.1

Primary end point(s)

The primary objective of the study is describe the pharmacodynamic analgesic profile (time of onset of meaningful analgesic effect, peak-effect, time to peak-effect, duration of effect) of intradermal doses of Dysport in subjects with abdominal or thoracic chronic scar pain. Therefore, the primary outcome measure is a composite of the following, based upon the Numerical Rating Scores (NRS) as recorded by the patients:
• Time to onset, i.e. time to decrease from baseline of two points in the spontaneous NRS score,
• Peak-effect, i.e. maximal decrease from baseline in the spontaneous NRS score,
• Time to peak-effect, i.e. time to reach the peak-effect,
• Duration of effect, i.e. duration between time to onset and last timepoint with change from baseline in the spontaneous NRS score is ≥ two points,
• Change from baseline in the spontaneous NRS score to each scheduled timepoint,
• Change from baseline in the stimulus-evoked NRS score to each scheduled timepoint.

E.5.1.1

Timepoint(s) of evaluation of this end point

The subjects will be assessed for up to 16 weeks post-dosing of Dysport or placebo.

E.5.2

Secondary end point(s)

The secondary and exploratory endpoints are:

Secondary
• To compare the efficacy of intradermal doses of Dysport to placebo.
• To assess the safety and tolerability of a range of intradermal doses of Dysport.
Exploratory
• To explore improvement of quality of life (QoL) using SF-36 questionnaire.
• To explore concomitant use of rescue medication (analgesia).

E.5.2.1

Timepoint(s) of evaluation of this end point

The subjects will be assessed for up to 16 weeks post-dosing of Dysport or placebo.

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

E.6.4

Safety

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)

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

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

Last patient last visit.

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