E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Sclerosis, scleroderma digital ulcers |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042953 |
E.1.2 | Term | Systemic sclerosis |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039710 |
E.1.2 | Term | Scleroderma |
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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 efficacy of treprostinil diethanolamine on net ulcer burden compared to placebo in patients with systemic sclerosis (SSc) |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of treprostinil diethanolamine as compared to placebo on: 1. Formation of new ischemic digital ulcers 2. Healing of active baseline ulcers 3. Digital ulcer related pain (as measured by Visual Analogue Scale [VAS-Pain] and Short Form McGill Pain Questionnaire [SF MPQ]) 4. Raynaud’s phenomenon (as measured by the Scleroderma Specific Raynaud’s Visual Analogue Scale [SSRVAS] -- a subcomponent of the Scleroderma Health Assessment Questionnaire [SHAQ]) 5.Patient function (as measured by the SHAQ and Cochin Hand Function Scale [CHFS]) 6.Skin thickening (as measured by the modified Rodnan Skin Score [mRSS]) 7.Patient quality of life (as measured by the SF 36) 8.Patient and physician global assessment of ulcer (as measured by patient impression of change questionnaire [PIC] and Visual Analogue Scale [VAS-Global]) 9. Vascular and SSc associated biomarkers
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Subject gives voluntary written informed consent to participate in the study. 2) Subject has been diagnosed with systemic sclerosis (SSc) as defined by American College of Rheumatology (ACR) criteria. 3) Males and females age greater than 18 years at time of Screening. 4)Presence of at least one active digital ulcer (meets protocol defined qualifications for active digital ulcer, Section 3.3.1.1) at Baseline. 5) Females of childbearing potential must be willing to use a reliable form of medically acceptable contraception and have a negative pregnancy test at Screening and confirmed at Baseline. Women who are surgically sterile or have been post-menopausal for at least 2 years are not considered to be of child-bearing potential. 6) Subject is able to communicate effectively with study personnel and be considered reliable, willing and cooperative in terms of compliance with the protocol requirements.
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E.4 | Principal exclusion criteria |
1)Has diagnosis of pulmonary arterial hypertension (PAH). 2)Body weight less than 40 kg at time of Screening, confirmed at Baseline. 3)The subject has a history of postural hypotension, unexplained syncope, a blood pressure that is less than 95 mmHg systolic or 50 mmHg diastolic at Screening or Baseline. 4)Hemoglobin concentration less than 75% of the lower limit of the normal range at time of Screening. 5)Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C. 6)Intractable diarrhea, or severe malabsorption, defined as greater than 15% unintentional loss of body weight in the last 6 months prior to Screening; any severe organ failure (e.g., lung, kidney), bleeding diathesis or platelet disorder, or any life-threatening condition. 7)Pregnancy or breast-feeding. 8) Simultaneously fulfills criteria for a second connective tissue disease including systemic lupus erythematosus, rheumatoid arthritis, or inflammatory myopathy 9)Sympathectomy of the upper limb performed within 12 months of Baseline. 10)Receipt of prostanoid treatment (epoprostenol, treprostinil sodium, or other prostacyclin analog) within the previous 3 months of Baseline for conditions including Reynaud’s phenomenon, rest pain and / or digital ulcers. 11)Patients who have required systemic antibiotics for infected digital ulcers within 2 weeks of Screening. 12)Local injection of botulinum toxin in an affected finger within 1 month prior to Baseline. 13)Treatment with endothelin receptor antagonists within 1 month prior to Baseline. 14)Treatment with phosphodiesterase inhibitors such as sildenafil, except for intermittent treatment of male erectile dysfunction. 15)Treatment with statin within 1 month prior to Screening, unless for management of hyperlipidemia. 16)Received an investigational product within 1 month preceding Screening. 17)Known hypersensitivity to treprostinil diethanolamine or any of the excipients. 18)Tobacco or nicotine use at any level within the past 6 months prior to Screening. 19)Any condition or laboratory value that in the opinion of the investigator might interfere with the subject's participation in the study, poses an added risk for the subject, could prevent understanding the objectives, nature, or consequences of the trial, compliance with the protocol, adherence to therapy or that would interfere with the interpretation of study assessments.
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction in net ulcer burden |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 2 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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Last visit of last subject undergoing trial |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |