Clinical Trials Register

Summary
EudraCT Number:	2017-001028-23
Sponsor's Protocol Code Number:	T1010-01
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-06-06
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2017-001028-23

A.3

Full title of the trial

Validation Study to Investigate the Effect of T4P1010 treatment in Patients with Osteoarthritic Pain of Knee or Hip.

Etude de validation de l’effet du traitement T4P1010 chez des patients souffrant de douleur ostéoathritique du genou ou de la hanche.

A.3.1

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

A Study to Validate a New Treatment in Patients with Chronic Pain Associated to Osteoarthritis.

Etude de validation d'un nouveau traitement chez des patients souffrant de douleurs chroniques dues à de l'athrose du genou ou de la hanche

A.4.1

Sponsor's protocol code number

T1010-01

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	Tools4Patient
B.1.3.4	Country	Belgium
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	Tools4Patient SA
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Tools4Patient SA
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	48, Rue Auguste Piccard
B.5.3.2	Town/ city	Gosselies
B.5.3.3	Post code	6041
B.5.3.4	Country	Belgium
B.5.6	E-mail	T1010-01@tools4patient.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	T4P1010
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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)	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	Yes
D.3.11.13.1	Other medicinal product type	No active substance; IMP made of cornstarch

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

Osteoarthritic pain of knee or hip.

Douleur osteoarthritique du genou ou de la hanche.

E.1.1.1

Medical condition in easily understood language

Chronic pain associated with osteoarthritis of knee or hip.

Douleur chronique due à de l'arthrose du genou ou de la hanche.

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

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	10023476
E.1.2	Term	Knee osteoarthritis
E.1.2	System Organ Class	100000004859

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	10020108
E.1.2	Term	Hips osteoarthritis
E.1.2	System Organ Class	100000004859

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 study the relationship between the patient’s profile (as defined by his/her disease history, personality characteristics, expectations, genetic profile and demographic characteristics) and his/her placebo response, as defined by the analgesic effect measured by Average Pain Score (APS) reduction after a placebo treatment on osteoarthritic (OA) pain of knee or hip.

Etudier la relation entre le profil du patient (tel que défini par l’historique de sa pathologie, sa personnalité, ses attentes, son profil génétique et ses caractéristiques démographiques) et sa réponse placebo, telle que définie par l’effet antalgique d’un placebo sur la douleur ostéoarthritique (DOA) du genou ou de la hanche, mesuré par la réduction de l’intensité de douleur moyenne (Average Pain Score ; APS) suite à un traitement placebo.

E.2.2

Secondary objectives of the trial

• To investigate the placebo effect compare to the control group.
• To assess the predictability of placebo response based upon draft algorithm developed in previous study.
• To study the relationship between the genetic variation of dopamine, serotonin, opioid and endocannabinoid pathways and the analgesic effect measured by APS reduction after T4P1010 treatment:
o Single nucleotide polymorphisms (SNPs) variation of catechol-O-
methyltransferase (COMT); monoamine oxidase; dopamine B hydroxylase; dopamine receptor 3 and brain-derived neurotropic factor genes;
o SNPs variation of tryptophan hydroxylase-2, 5-Hydroxytryptamine transporter and 5-Hydroxytryptamine receptor 2A;
o SNP variation of opioid receptor mu 1 gene;
o SNP variation of fatty acid amide hydrolase gene.
• To assess the stability of the MPSQ over trial duration.

• Evaluer l’effet placebo par comparaison avec le groupe contrôle.
• Evaluer la prédictibilité de la réponse placebo en se basant sur l’algorithme développé grâce à l’étude précédente.
• Evaluer la relation entre les variations génétiques de la voie dopaminergique, de la voie sérotoninergique, de la(les) voie(s) activée(s) par les opioïdes et/ou cannabinoïdes endogènes et l’effet antalgique mesuré par la diminution de l’intensité de l’APS suite au traitement T4P1010: polymorphisme nucléotidique des gènes
o catéchol-O-méthyltransférase (COMT), monoamine oxydase, dopamine beta-hydroxylase, récepteur D3 de la dopamine et facteur neurotrophique dérivé du cerveau;
o tryptophane hydroxylase-2, transporteur 5-hydroxytryptamine et récepteur 5-hydroxytryptamine 2A;
o récepteur opiacé mu 1;
o hydrolase des amides d'acides gras.
• Evaluer la stabilité du questionnaire de caractérisation de l’effet placebo (MPSQ) sur la durée de l’étude.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Men or women of at least 18 years of age.
• OA of knee or hip diagnosed since at least 6 months.
• Pain scores reported during the baseline period preceding randomization
with a mean APS on the last 14 reported values before Visit 2 between 3.6 and 8.4 inclusive and to have completed at least 2/3 of each pain score in their diary between Visit 1 and Visit 2.
• Patient with a unilateral or bilateral OA of the knee or hip diagnosed according to the American College of Rheumatology (ACR) criteria based on clinical and radiographic evidence (Altman et al., 1986) (in case of bilateral OA or OA of both knee and hip, the joint to consider should be the most affected one). The clinical diagnosis of OA will be confirmed by the ACR clinical criteria and medical imaging criteria for classification of OA of the knee or hip based upon the following criteria:
a. Knee or hip pain as an average at least half of the time for the last 3 months before screening visit.
b. OA of the knee, at least 1 of the following 3 conditions:
i. age > 50,
ii. morning stiffness <30 minutes,
iii. crepitus on active motion and osteophytes.
OA of the hip, at least 2 of the following 3 conditions:
i. erythrocyte sedimentation rate (ESR) < 20mm/hour,
ii. femoral and/or acetabular osteophytes,
iii. joint space narrowing (superior, axial, and/or medial).
c. Kellgren and Lawrence grade > 1 as assessed by a recent medical imaging of the referred joint to confirm the diagnosis. If no imaging available, a new anterior- posterior view will be obtained and reviewed by Investigator or his/her delegate(s) to verify that the patient meets the disease diagnostic criteria.

• Hommes ou femmes d'au moins 18 ans.
• Diagnostic de DOA du genou ou de la hanche posé depuis au moins 6 mois.
• Présentant un score moyen compris entre 3,6 et 8,4 inclus pour les 14 derniers APS rapportés avant la Visite 2 et ayant complété au moins 2/3 de chacun des scores devdouleur dans leur carnet entre la Visite 1 et la Visite 2.
• Ostéoarthrite (OA) unilatérale ou bilatérale du genou ou de la hanche diagnostiquée selon les critères de l’American College of Rheumatology (ACR) basé sur des données cliniques et radiographiques (Altman et al., 1986) (dans le cas d’une OA bilatérale ou d’une OA à la hanche et au genou, l’articulation la plus affectée est à considérer). Le diagnostic clinique de l’OA sera confirmé par les critères cliniques et d’imagerie médicale de l’ACR suivants:
a. Douleur de la hanche ou du genou en moyenne au moins la moitié du temps les 3 mois précédant la Visite 1.
b. OA du genou, au moins une des 3 conditions suivantes:
i. âge > 50,
ii. raideur le matin <30 minutes,
iii. crépitation lors de mouvement et ostéophytes.
OA de la hanche, au moins 2 des 3 conditions suivantes:
i. vitesse de sédimentation (VS) < 20mm/heure,
ii. ostéophytes au niveau du fémur et/ou de l’acetabulum,
i. pincement de l'interligne articulaire (supérieur, axial et/ou médian).
c. Grade Kellgren and Lawrence > 1 tel qu’évalué récemment par imagerie médicale de l’articulation touchée pour confirmer le diagnostic. En l’absence de donnée récente d’imagerie médicale, une nouvelle vue antéro-postérieure sera obtenue et revue par l’Investigateur ou son délégué pour vérifier que le patient rencontre bien le critère diagnostic.

E.4

Principal exclusion criteria

• Change in the « regular analgesic therapy » or introduction of a « regular analgesic therapy » (if none beforehand) for OA in the last 4 weeks prior to Visit 1 or during the study.
• Invariable pain scores reported between Visit 1 and Visit 2.
• Pregnant, breastfeeding, or willing to be pregnant during the study.
• Patients with a current or recent history, as determined by the Investigator,
a. of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, or cerebral disease;
b. any known hypersensitivity to corn and/or corn-derived products;
which would interfere with the patient's participation in the study.
• Any other relevant medical disorder/acute disease state/pain condition like fibromyalgia, lombalgia, generalized OA judged by the Investigator as likely to interfere with the trial or represent a risk for the patient.
• Having completed or withdrawn from this study or any study investigating T4P1001.
• Have planned total knee or hip replacement intervention of the referred joint.
• Reduced mobility due to OA (use of lower extremity assistive devices other than a cane or a knee sleeve such as crutches or walker or a knee brace or a “shoe lift” in relation to OA is not allowed).
• Use or plan to use systemic corticosteroids 4 weeks prior to Visit 1 or during the study; Intra-muscular corticosteroid injections or Intra-articular injection of steroids into the referred knee/hip within 3 months before Visit 1 or during the study; Intra-articular injection of corticosteroids into any other sites than the referred knee/hip within 4 weeks prior to Visit 1 or during the study (corticosteroids in topical use are allowed).
• Have used viscosupplementation or intra articular injection of hyaluronic acid in the referred joint within 3 months prior to Visit 1 or plan to use during the study.

• Changement ou introduction du « traitement antalgique régulier » pour la DOA endéans les 4 semaines précédant la Visite 1 ou pendant l’étude.
• Ayant rapporté des scores de douleur invariables entre la Visite 1 et la Visite 2.
• Femme enceinte, allaitant, ou désireuse d’etre enceinte pendant l’étude.
• Histoire récente ou en cours, telle que déterminée par l'investigateur,
a. de maladie rénale, hépatique, hématologique, gastro-intestinale, endocrinienne, pulmonaire, cardiaque, neurologique ou cérébrale grave, progressive, et/ou incontrolée,
b. de toute hypesensibilité connue au maïs ou à ses produits dérivés,
qui pourrait interférer avec la participation du patient dans l'étude.
• Tout autre trouble médical pertinent/état aigu/condition douloureuse telle que fibromyalgie, lombalgie, OA généralisée jugé par l’Investigateur comme pouvant interférer avec l’étude ou représenter un risque pour le patient.
• Ayant terminé ou participé à cette étude ou tout étude étudiant le T4P1001.
• Ayant prévu une intervention chirurgicale visant à remplacer l’articulation touchée.
• Utilisation en relation avec l’OA de dispositifs d’assistance pour les extrémités autres qu’une cane ou qu’une simple genouillère tels que béquilles, tribune, attelle ou dispositif
orthopédique.
• Ayant utilisé pour la DOA des corticoides systémiques 4 semaines avant la Visite 1 ou prévoyant d’en utiliser pendant l’étude; des injections intra-musculaires ou intra- articulaires de corticoides dans l’articulation touchée les 3 mois précédant la Visite 1 ou prévoyant d’en utiliser pendant l’étude; des injections intra-articulaires de corticoides dans tout autre site que l’articulation touchée les 4 semaines précédant la Visite 1 ou prévoyant d’en utiliser pendant l’étude (les corticoides en usage topique sont permis).
• Ayant eu une viscosupplémentation ou des injections intra-articulaires d’acide hyaluronique dans l’articulation touchée les 3 mois précédant la Visite 1 ou en planifiant pendant l’étude.

E.5 End points

E.5.1

Primary end point(s)

Patient’s change from baseline of pain severity, as measured by the weekly means of the daily APS in the last 24 hours in patients with OA pain of knee or hip during a 12-week treatment therapy period.

Changement par rapport aux valeurs de référence d'intensité de douleur telles que mesurées par la moyenne hebdomadaire des scores d'APS
quotidiens chez des patients souffrant de douleur ostéoarthritique du genou ou de la hanche durant une période de traitement de 12 semaines.

E.5.1.1

Timepoint(s) of evaluation of this end point

APS: from Visit 1 to Visit 5.

APS: de la visite 1 à la Visite 5.

E.5.2

Secondary end point(s)

• Analgesic outcomes:
o The patient’s change from baseline of pain severity as measured by the
weekly means of the worst pain score (WPS) in the last 24 hours;
o The patient’s change from baseline of pain severity as measured by the
weekly means of the least pain score (LPS) in the last 24 hours;
o The patient’s change from baseline of condition as measured by the
western Ontario and McMaster universities arthritis index (WOMAC);
o The patient’s change from baseline of pain severity as measured by the
brief pain inventory (BPI);
o The patient’s change from baseline of pain severity as measured by the
intermittent and constant osteoarthritis pain (ICOAP) questionnaire;
o The patient’s change from baseline of patient and Investigator global
assessment of changes (PGAC and IGAC).
• Personality characteristics outcomes:
o To assess the Crombach α of the MPSQ between the end and the start of study.

• Antalgique:
o Changement par rapport aux valeurs de référence de l'intensité de douleur telles que mesurées par la moyenne hebdomadaire du pire score de douleur (WPS) pendant les dernières 24 heures;
o Changement par rapport aux valeurs de référence de l'intensité de douleur telles que mesurées par la moyenne hebdomadaire du score de douleur le plus faible (LPS) pendant les dernières 24 heures;
o Changement par rapport aux valeurs de référence de la condition telles que mesurées par le Western Ontario and McMaster Universities Arthritis Index (WOMAC);
o Changement par rapport aux valeurs de référence de l'intensité de douleur telles que mesurées par le Brief Pain Inventory (BPI);
o Changement par rapport aux valeurs de référence de l'intensité de douleur telles que mesurées par le questionnaire intermittent and constant osteoarthritis pain (ICOAP);
o Changement par rapport aux valeurs de référence du Patient Global Assessment of Changes (PGAC) et du Investigator Global Assessment of Changes (IGAC).
• Caractéristiques de personnalité:
o Evaluer le Crombach α du MPSQ entre le début et la fin de l'étude.

E.5.2.1

Timepoint(s) of evaluation of this end point

• Analgesic outcomes:
o WPS: daily between Visit 1 and Visit 5;
o LPS: daily between Visit 1 and Visit 5;
o WOMAC: at each visit;
o BPI: at each visit;
o ICOAP: at Visit 2, 3, 4 and 5;
o PGAC and IGAC: at each visit.
• Personality characteristics outcomes:
o MPSQ: at Visit 2 and Visit 5.

• Antalgique:
o WPS: quotidiennement entre la Visite 1 et la Visite 5;
o LPS: quotidiennement entre la Visite 1 et la Visite 5;
o WOMAC: à chaque visite;
o BPI: à chaque visite;
o ICOAP: aux Visites 2, 3, 4 et 5;
o PGAC and IGAC: à chaque visite.
• Caractéristiques de personnalité:
o MPSQ: à la Visite 2 et à la Visite 5.

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

E.6.6

Pharmacokinetic

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

Yes

E.6.13.1

Other scope of the trial description

Psycho-sociology

Psycho-sociologie

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Groupe actif et groupe contrôle où dans le groupe actif, les patients recevront du placebo.

Active group and control group study where in the active group, patients will receive placebo.

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.8.5

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

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

End of the trial when approximately 66 patients (approximately 55 in the active group and 11 in the control group) complete the study.

Fin d'étude définie lorsqu'approximativement 66 patients terminent l’étude (approximativement 55 dans le groupe actif et 11 dans le groupe contrôle).

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:

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.

Aucun.

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

2017-06-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-08-02

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-08-24

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