E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Calciphylaxis (calcific uremic arteriolopathy [CUA]) |
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E.1.1.1 | Medical condition in easily understood language |
Rare disease of calcification of the small blood vessels in the fatty tissue and deeper layers of the skin. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
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 evaluate the efficacy of SNF472 compared with placebo when added to background care for the treatment of CUA • To evaluate the safety and tolerability of SNF472 compared with placebo when added to background care for the treatment of CUA |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥18 years of age 2. Receiving maintenance HD in a clinical setting for at least 2 weeks prior to screening 3. Clinical diagnosis of CUA by the Investigator including ≥1 CUA lesion with ulceration of the epithelial surface. A central wound rating group will review wound images to confirm the primary lesion is due to CUA. 4. CUA wound-related pain shown by a Pain VAS score ≥50 out of 100 5. Primary lesion that can be clearly photographed for the purpose of protocol-specified wound healing assessments 6. Willing and able to understand and sign the informed consent form and willing to comply with all aspects of the protocol |
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E.4 | Principal exclusion criteria |
1. Subjects whose primary lesion is due to causes other than CUA 2. History of treatment with bisphosphonates within 3 months of baseline (Week 1 Day 1) 3. Severely ill subjects without a reasonable expectation of survival for at least 6 months based on the assessment of the Investigator 4. Subjects with a scheduled parathyroidectomy during the study period 5. Expectation for kidney transplant within the next 6 months based on Investigator assessment or identification of a known living donor 6. Pregnant or trying to become pregnant, currently breastfeeding, or of childbearing potential (including perimenopausal women who have had a menstrual period within one year) and not willing to either completely avoid sexual intercourse with a person of the opposite sex or use a highly effective method of birth control from screening through at least 30 days after last dose of study drug 7. Significant noncompliance with dialysis treatment evidenced by repeated missed dialysis sessions (including if due to hospitalizations where dialysis treatment is unavailable) or significant noncompliance with medication regimen, in the judgment of the Investigator 8. Any history of active malignancy within the last year (history of localized basal cell or squamous cell carcinoma that has been excised/appropriately treated or a fully excised malignant lesion with a low probability of recurrence will not be considered exclusionary) 9. Clinically significant illness other than CUA within 30 days prior to screening that, in the judgment of the Investigator, could interfere with interpretation of study results, impair compliance with study procedures, or impact the safety of the subject (e.g., unstable angina, unstable heart failure, stroke, uncontrolled hypertension, or other illness requiring hospitalization) 10. Participation in an investigational study and receipt of an investigational drug or investigational use of a licensed drug (with the exception of intravenous STS) within 30 days prior to screening. If participating in an investigational study of intravenous STS, all visits of that study must be completed prior to screening for this study. Note: Off-label use of intravenous STS outside of an investigational study is not restricted. 11. Past or current participation in another clinical study with SNF472 12. History or presence of active alcoholism or drug abuse as determined by the Investigator within 6 months before screening or concurrent social conditions that, in the opinion of the Investigator, would potentially interfere with the subject's study compliance 13. Mental impairment or history of or current significant psychiatric disease that, in the opinion of the Investigator, may impair ability to provide informed consent or impact compliance with study procedures 14. Any other condition or circumstance that, in the opinion of the Investigator, may make the subject unlikely to complete the study or comply with study procedures and requirements, or may pose a risk to the subject's safety and well-being 15. Subjects whose CUA lesions exhibit significant improvement, in the opinion of the Investigator, between the first and second screening visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints; Applies to part 1. These endpoints will compare the placebo and SNF472 groups as follows;
Alternate Primary Efficacy Endpoints: • Absolute change from baseline to Week 12 in the BWAT-CUA score for the primary lesion • Absolute change from baseline to Week 12 in Pain VAS score
Safety Endpoints; Applies throughout part 1 and part 2 • Proportion of subjects with AEs, SAEs, and deaths • Changes from baseline in the following: o Laboratory parameters o QTc interval and other ECG parameters o Holter monitoring results o Vital signs • Proportion of subjects with a CUA wound-related infection, sepsis, hospitalization, or any CUA wound-related complication |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy (Part 1): Various timepoints from baseline to week 12 Safety: Proportion of subjects with AEs, SAEs, and deaths • Changes from baseline in the following: ▪ Laboratory parameters ▪ QTc interval and other ECG parameters ▪ Holter monitoring results ▪ Vital signs • Proportion of subjects with a CUA wound-related infection, sepsis, hospitalization, or any CUA wound-related complication |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints (assessed hierarchically): • Absolute change from baseline to Week 12 in the Wound-QoL score • Absolute change from baseline to Week 12 in the BWAT total score for the primary lesion • Qualitative wound image evaluation for the primary lesion (worsened, equal to, or improved relative to baseline) at Week 12 • Rate of change in opioid use as measured in morphine milligram equivalents (MME) from baseline to Week 12 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Various timepoints from baseline to week 12 |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Belgium |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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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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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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |