E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progressive multiple sclerosis, both primary and secondary progressive |
Progressieve multipele sclerose, zowel primair als secundair progressief |
|
E.1.1.1 | Medical condition in easily understood language |
Multipele sclerosis |
Multipele sclerose |
|
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 | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063401 |
E.1.2 | Term | Primary progressive multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063400 |
E.1.2 | Term | Secondary progressive multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053395 |
E.1.2 | Term | Progressive multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The aim of this pilot study is to determine whether uptake op the TSPO radioligand [18f}DPA-714 can be quantified in the cortex and/or hippocampus in vivo to discriminate progressive MS patients from controls. |
De primaire uitkomstmaat is het kwantificeren van het bindingspotentiaal van [18F]DPA-714 in de cortex en hippocampus in vivo en het onderscheid dat hiermee gemaakt kan worden tussen progressieve MS patiënten en gezonde controle personen. |
|
E.2.2 | Secondary objectives of the trial |
Secondarily we will determine whether:
1. Labeled microglial cells co-localize with MRI detected GML and cortical thinning.
2. Binding in cortex and/or hippocampus correlates with clinical disability and cognitive decline in progressive MS patients. |
1. De co-localisatie van de gelabelde microglia zoals afgebeeld met PET scan en de grijze stof lesies en corticale atrofie zoals gezien op de MRI scan.
2. De correlatie tussen de hoeveelheid binding van de tracer in de cortex en/of hippocampus en de hoogte van de scores op de neurologische en cognitieve testen. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- For the MS patient group: diagnosis primary or secondary progressive MS with EDSS scores 4.0 to 7.5 - 18 to 60 years
- Written informed consent
- No immunomodulating or immunosuppressive treatment in previous three months |
- Voor de MS patiënten groep: diagnose primair of secundair progressieve MS met een EDSS score van 4.0 tot 7.5
- 18 tot 60 jaar
- Ondertekend informed consent
- Geen immunomodulerende of immunosuppressieve behandeling in voorafgaande drie maanden |
|
E.4 | Principal exclusion criteria |
- Inability to undergo MRI, e.g. metal objects in or around the body, claustrophobia or inability to lie still in the scanner. For the MS patients: contra-indication for gadolinium administration, e.g. previous allergic reaction to gadolinium.
- Homozygote Ala(147)Thr genotype (low-affinity binders)
- Significant immune disease other than MS
- (History of) other relevant neurological disease
- History of malignancy
- Known significant cardiac disease
- Inadequate renal function: creatinine clearance <60 ml/min
- Loss or donation of blood over 500 mL within four months prior to screening.
- In male subjects Hb < 8.0 g/dL, in female subjects Hb < 7.0 g/dL
- Pregnant or breast feeding
- (History of) alcohol and/or drug abuse
- Exposure to previous radiation leading to annual cumulative dose of more than 10 mSV if participating in this protocol
- Use of benzodiazepines within 1 week of the PET scan |
- Niet mogelijk om MRI te ondergaan, zoals bij een metaal voorwerp in het lichaam, claustrophobie of niet sil kunnen liggen in de scanner. Bij de MS patiënten: contra-indicatie voor toedienen gadolinium, zoals een eerdere allergische reactie op gadolinium
- Homozygoot genotype Ala(147)Thr
- Significante immuun aandoening anders dan MS
- (Voorgeschiedenis met) andere relevante neurologische ziekte of aandoening
- Oncologische voorgeschiedenis
- Bekende relevante hart aandoening
- Inadequate nierfunctie: creatinine klaring <60 ml/min
- Verlies of donatie van bloed van meer dan 500cc in de 4 maanden voorafgaande aan screening
- Bij mannen Hb <8.0 g/dL, bij vrouwn Hb <7.0 g/dL
- Zwanger of borstvoeding gevend
- (Voorgeschiedenis) alcohol en/of drugs misbruik
- Eerdere stralingsbelasting waardoor de jaarlijkse cumulatieve dosering meer dan 10 mSV zou worden bij deelname aan deze studie
- Gebruik van een benzodiazepine in de week voorafgaande aan de PET scan |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The main study parameter is the [18F]DPA-714 binding potential (BP) which will be assessed in PPMS and SPMS patients and healthy control subjects with validated tracer kinetic models. BP is a measurement of microglial activation. |
De primaire uitkomstmaat is het bindings potentiaal (BP) van [18F]DPA-714 geanalyseerd in de primaire en secundair progressieve MS patiënten en de gezonde controles middels gevalideerde tracer kinetiek modellen. BP is hierin een maat van microglia activatie. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The BP will be assessed from the data collected during the 60 minute [18F]DPA-714 PET scan. Each patient and control subject will undergo one PET scan and therefore one administration of the tracer. |
Het BP zal geanalyseerd worden aan de hand van de data verzameld tijdens de 60 minute durende [18F]DPA-714 PET scan. Elke patiënt en gezonde controle zal één PET scan ondergaan en daarbij een eenmalige toediening van de tracer. |
|
E.5.2 | Secondary end point(s) |
- The relation between [18F]DPA-714 BP in the cerebral cortex and/or hippocampus and MRI detected grey matter lesions and cortical thinning.
- The relation between [18F]DPA-714 BP in the cerebral cortex and/or hippocampus and clinical disability and cognitive decline in progressive MS patients as measured with the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC) and Symbol Digit Modalities Test (SDMT). |
- De relatie tussen [18F]DPA-714 BP in de cerebrale cortex en/of hippocampus en de MRI gedetecteerd grijze stof lesies en cortical atrofie.
- De relatie tussen [18F]DPA-714 BP in de cerebrale cortex en/of hippocampus en klinische en cognitieve uitkomstmaten gemeten op de Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC) and Symbol Digit Modalities Test (SDMT). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Each patient and control will have three visits in a fixt order: 1. screening session 2. MRI scan 3. PET scan.
The end points will be evaluated after completion of these three visits. |
Elke patiënt en gezonde controle heeft drie visits in een vaste volgorde: 1. screening sessie 2. MRI scan 3. PET scan.
De uitkomstmaten zullen geanalyseerd worden na voltooiing van alle drie de visits. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |