E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complex regional pain syndrome |
|
E.1.1.1 | Medical condition in easily understood language |
Complex regional pain syndrome type 1 is a chronic pain syndrome of the extremities, that often follows minor trauma or surgeries. Patients suffer from severe and often chronic pain and disability. |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Biological Phenomena [G16] |
MedDRA Classification |
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 |
To assess the safety, and ability of subcutaneously administered ARA 290 to reduce pain, assessed by Numerical Rating Score of "pain now" and Global Health self-assessment, during and after 4 weeks of treatment with ARA 290 or placebo |
|
E.2.2 | Secondary objectives of the trial |
• Assess the predictive effect of sensory tests as determined by quantitative sensory testing (QST, for example deep muscle pressure pain threshold) on the efficacy of treatment;
• Assess the effect of ARA 290 treatment on quality of life and overall mood-related parameters;
• Assess the effect of ARA 290 on daily functioning
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1) Continuing pain, which is disproportionate to any inciting event;
(2) Must report at least one symptom in three of the four following categories:
a. Sensory: reports of hyperesthesia and/or allodynia;
b. Vasomotor: reports of temperature asymmetry and/or skin color changes and/or color asymmetry;
c. Sudomotor/edema: reports of edema and/or sweating changes and sweating asymmetry;
d. Motor/trophic: reports of decreased motor ranges and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin);
(3) Must display at least one sign at time of evaluation in two or more of the following categories:
a. Sensory: hyperalgesia (to pinprick) and/or allodynia (to light touch and/or deep somatic pressure and/or joint movement);
b. Vasomotor: evidence of temperature asymmetry and/or skin color changes and/or color asymmetry;
c. Sudomotor/edema: evidence of edema and/or sweating changes and sweating asymmetry;
d. Motor/trophic: evidence of decreased motor ranges and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin);
(4) There is no other diagnosis that better explains the signs and symptoms.
(5) Pharmacotherapy for CRPS symptoms (e.g., analgesics, antidepressants, and/or anticonvulsants ) has been stable for at least 4 weeks
|
|
E.4 | Principal exclusion criteria |
• Inability to give informed consent;
• Patients suffering from other pain syndromes;
• Clinically relevant abnormal history of physical and mental health, as determined by medical history taking and physical examinations obtained during the screening visit and/or prior to the administration of the initial dose of the study drug (as judged by the investigator);
• A semi recumbent systolic blood pressure of >160 mmHg and/or diastolic blood pressure of > 95 mmHg at screening;
• History of alcoholism or substance abuse within three years prior to screening;
• Positive pregnancy test or lactation
• Male subjects habitually using more than 21 units of alcohol per week and female subjects using more than 14 units of alcohol per week;
• Subject has a history of severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food;
• Subjects that received a vaccination or immunization within the last month;
• Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug or more than 4 times per year;
• Subject has undergone major surgery within three months prior to screening;
• Inability or unwillingness to self-administer ARA 290 via subcutaneous injections
• Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The main study end-point is:
• Change in Numerical Rating Score of “pain now” as reported at the end of each treatment week and at the end of each week in the 4 weeks following treatment.
• Global Health self-assessment
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pre-treatment and at the end of each week for the four weeks of treatment and continuing weekly for an additional 4 weeks. |
|
E.5.2 | Secondary end point(s) |
Additional endpoints are:
• Change in Brief Pain Inventory
• Change in Short Form-36 questionnaire
• Change in Radboud Skills Questionnaire
• Change in the Walking Ability questionnaire
• Change in Hospital Anxiety and Depression Scale
• Change in Pain Coping Inventory
• Change in analgesic/antidepressant use
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pre-treatment and at the end of each week for the four weeks of treatment and continuing weekly for an additional 4 weeks. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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
|
The study will end prematurely in case the investigators in close cooperation with the ethics committee decide this. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |