E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Uremic Pruritus |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to Severe Uremic Pruritus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
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 | 10060884 |
E.1.2 | Term | Uremic pruritus |
E.1.2 | System Organ Class | 100000004858 |
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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 |
To compare the efficacy of orally administered DS107 versus placebo, in the treatment of adult haemodialysis patients with moderate to severe Uremic Pruritus (UP). |
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E.2.2 | Secondary objectives of the trial |
To assess the safety of orally administered DS107 versus placebo, in adult haemodialysis patients with UP. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Limited pharmacokinetics of dihomo-gamma-linolenic acid (DGLA) at Baseline, Week 2, Week 4 and Week 12 (selected centres, only) with blood withdrawals at trough, 4 hours, 23 hours and 24 hours post investigational medicinal product (IMP) administration.
Total fatty acid analysis (selected centres only) with samples to be taken at Baseline, Week 4 and Week 12. |
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E.3 | Principal inclusion criteria |
1. Male or female patients who are aged 18 years and older on the day of signing the informed consent form (ICF). 2. Patients who are on stable haemodialysis 3 times a week for at least 3 months prior to screening with a urine production of less than 300 ml per day. 3. Patients with continued (uncontrolled) pruritus despite standard of care in the institution. 4. Patients with moderate to severe pruritus, as determined by qualifying mean worst NRS score in a day of ≥5 (on 11 point NRS) at the screening visit. 5. Female patients and male patients with female partners of child bearing potential must use highly effective birth control methods or have a sterilised partner for the duration of the study. Highly effective birth control methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include systemic hormonal contraceptives, intrauterine device or sexual abstinence. Note: Hormonal contraceptives must be on a stable dose for at least one month before baseline. Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject 6. Patients whose pre-study clinical laboratory findings do not interfere with their participation in the study, in the opinion of the Investigator. 7. Patients who are able to communicate well with the Investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent. |
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E.4 | Principal exclusion criteria |
1. Patients who are known to be non-compliant with dialysis treatment (i.e., has missed more than 2 dialysis sessions in the past 2 months because of non-compliance). 2. Patients who are anticipated to receive a kidney transplant during the study. 3. Patients on peritoneal dialysis. 4. Patients with substantial residual renal output (>300 ml per day). 5. Patients with pruritus only during the dialysis session (by patient report). 6. Patients with pruritus probably or definitely attributed to a cause other than end stage renal disease or its complications (e.g., patients with concomitant pruritic dermatological disease or cholestatic liver disease will be excluded). 7. Patients with a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the reference upper limit of normal (ULN), or total bilirubin greater than 2 times ULN at screening. 8. Patients with a history of clinically significant drug or alcohol abuse in the opinion of the investigator in the last year prior to Baseline (Day 0). 9. Patients using any topical agents with potential antipruritic activity, excluding emollients, during the 2 weeks before the baseline visit. 10. Patients with systemic antipruritic treatment during the 2 weeks before the baseline visit. Second and third generation oral antihistamines are allowed if the patient is on stable dose of antihistamine and this dose is not changed during the study period. First generation oral antihistamines are disallowed. 11. Patients on immuno-suppressant treatment such as Cyclosporine A (CsA), Methotrexate, Glucocorticoid steroids and similar compounds. 12. Patients who have received ultraviolet B treatment in the 4 weeks prior to the start of Screening or anticipated to receive such treatment during the study. 13. Patients who have participated in any other clinical study with an investigational medicinal product (IMP) within 3 months before the first day of administration of study treatment. 14. Patients who are pregnant, planning pregnancy, breastfeeding and/or are unwilling to use adequate contraception (as specified in inclusion criterion 5) during the trial. 15. Patients, in the opinion of the Investigator, not suitable to participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in worst-itching over the last 24 hours on the 11- point Numerical Rating Scale (NRS) in DS107 treated population compared to placebo at Week 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change from baseline in mean itching over the last 24 hours on the 11 point NRS in DS107 treated population compared to placebo at Week 2, 4, 6, 8, 10, 12 and 14.
Change from Week 12 (end of treatment/early termination visit) in worst-itching on the 11-point NRS in DS107 treated population compared to placebo at Week 14 (follow-up).
Change from baseline in worst-itching on the 11-point NRS in DS107 treated population compared to placebo at Week 2, 4, 6, 8, 10 and 14.
Percentage of patients achieving improvement of worst-itch pruritus of at least 2.7 points based on NRS at Week 2, 4, 6, 8, 10, 12 and 14.
Change from baseline in worst itching on the Dynamic Pruritus Score (DPS) in DS107 treated population compared to placebo at Week 2, 4, 6, 8, 10, 12 and 14.
Change from baseline in ItchyQoL assessment in DS107 treated population compared to placebo population from baseline to Week 2, 4, 6, 8, 10, 12 and 14.
Change in sleep quality assessment in DS107 treated population compared to placebo population from baseline to Week 2, 4, 6, 8, 10, 12 and 14.
Change in xerosis scoring in DS107 treated population compared to placebo population from baseline to Week 2, 4, 6, 8, 10, 12 and 14.
Change from baseline to Week 2, 4, 6, 8, 10, 12 and 14, in worst-itching on the 11-point NRS in the DS107 treated population compared to placebo treated sub-populations of subjects with a normal white blood cell count defined by a white blood cell (WBC) count of 3.5 -11.1 x109/L and a Neutrophil count of 1.8 -7.0 x109/L
Change from baseline to Week 2, 4, 6, 8, 10, 12 and 14, in worst-itching on the 11-point NRS in the DS107 treated population compared to placebo treated sub-populations of subjects with a normal eosinophil count (< 0.3 x109/L).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 2, 4, 6, 8, 10, 12 and 14 |
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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 | 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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | No |
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 |
Estonia |
Georgia |
Germany |
Latvia |
Poland |
Ukraine |
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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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |