Calcific Uremic Arteriolopathy, Calciphylaxis
Conditions
Keywords
Calciphylaxis, Calcific Uremic Arteriolopathy, Dialysis, End Stage Renal Disease, Rare disease (ORPHA280062), Calcification, Calcium Metabolism Disorders, Calcinosis, Metabolic Diseases
Brief summary
To evaluate the effect of SNF472 on top of standard of care on promoting wound healing and other parameters of therapeutic response in haemodialysis patients with calciphylaxis (calcific uraemic arteriolopathy, CUA).
Interventions
DRUGSNF472
SNF472 for calciphylaxis
Sponsors
Sanifit Therapeutics S. A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with either newly diagnosed CUA OR recurrent CUA that has been dormant with no skin lesion involvement for at least 90 days from study start (new or recurrent diagnosis must be made within 5 weeks of study start) 2. Patients who signed the written informed consent to participate in this clinical trial (prior to any clinical trial-related procedures being performed), after reading the Patient Information Sheet and Informed Consent Form (ICF), and who had the opportunity to discuss the clinical trial with the Investigator or designee 3. Males or females aged ≥18 4. Patients on maintenance haemodialysis (HD) 5. Patients with at least a minimum level of pain on Visual Analog Scale (VAS) scale or on pain-killers stronger than non-steroidal anti-inflammatory drugs (NSAIDs) 6. Females of child-bearing potential should use a highly effective contraceptive measure throughout the study and have a negative serum pregnancy test at entry. Male patients having sexual relationship in which pregnancy can occur should take adequate contraceptive precautions (wear a condom)
Exclusion criteria
1. Body weight above 150 kg 2. BMI \>35 and central(abdominal) ulcers 3. History of bisphosphonate treatment within 12 months before entering into the study 4. Severely ill patients without reasonable expectation of survival for \> 6 months according to the treating physician 5. Patients with scheduled parathyroidectomy during the run-in or study period 6. Female patients who are either intending to get pregnant or are undergoing treatment to get pregnant, as well as breast-feeding females 7. Participation in another clinical trial with an experimental drug within 90 days prior the inclusion 8. Any psychological, emotional problems, any disorders or resultant therapy that is likely to invalidate informed consent, or limit the ability of the patient to comply with the Clinical Trial Protocol requirements 9. Patients who, in the opinion of the Investigator, are considered unsuitable for any other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Wound Healing | 12 weeks | Absolute change in Bates-Jensen Wound Assessment (BWAT) total score between baseline (Week 1) and Week 12 for the primary lesion (the largest one). The Bates-Jensen Wound Assessment (BWAT) is a standardized tool for quantitative assessment of wound healing that includes the 13 items listed below. * Size * Depth * Edges * Undermining or pockets * Necrotic tissue type * Necrotic tissue amount * Exudate type * Exudate amount * Surrounding skin color * Peripheral tissue edema * Peripheral tissue induration * Granulation tissue * Epithelialization Each item was rated on a scale of 1 (best) to 5 (worst). The Bates-Jensen Wound Assessment (BWAT) total score is the sum of the individual items with a possible range of 13 (best) to 65 (worst). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wound Pain | 12 weeks | Absolute change from baseline (Week 1) and Week 12 in the Pain Visual Analogue Scale (VAS) Score. The Pain Visual Analogue Scale (VAS) Score is a horizontal line, 100 mm in length, anchored by word descriptors at each end. The subject marked the point on the line that represented his/her perception of his/her current pain status. The Pain Visual Analogue Scale (VAS) Score was determined by measuring in millimeters from the left hand end of the line (no pain) to the point that the subject marked. The Pain Visual Analogue Scale (VAS) Score range 0 (best) to 100 (Worst). |
| Wound-QoL Global Score | 12 weeks | Absolute change from baseline (Week 1) and Week 12 in the Wound-QoL global score. The Wound-QoL questionnaire measures the disease-specific, health related QoL of patients with chronic wounds. It consists of 17 items on impairments that are assessed in retrospect to the preceding 7 days and rated on a 0 (best) to 4 (worse) scale with possible responses from not at all to very much. The total score is the average of the 17 responses. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SNF472 SNF472 for calciphylaxis | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Withdrawal by Subject | 1 |
| Overall Study | Withdrawal from HD | 1 |
Baseline characteristics
| Characteristic | SNF472 |
|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 14.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United Kingdom | 1 participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 14 |
| other Total, other adverse events | 13 / 14 |
| serious Total, serious adverse events | 7 / 14 |
Outcome results
Primary
Wound Healing
Absolute change in Bates-Jensen Wound Assessment (BWAT) total score between baseline (Week 1) and Week 12 for the primary lesion (the largest one). The Bates-Jensen Wound Assessment (BWAT) is a standardized tool for quantitative assessment of wound healing that includes the 13 items listed below. * Size * Depth * Edges * Undermining or pockets * Necrotic tissue type * Necrotic tissue amount * Exudate type * Exudate amount * Surrounding skin color * Peripheral tissue edema * Peripheral tissue induration * Granulation tissue * Epithelialization Each item was rated on a scale of 1 (best) to 5 (worst). The Bates-Jensen Wound Assessment (BWAT) total score is the sum of the individual items with a possible range of 13 (best) to 65 (worst).
Time frame: 12 weeks
Population: Subjects who received at least 1 dose of SNF472 and had at least 1 postbaseline efficacy measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SNF472 | Wound Healing | -8.1 units on a scale | Standard Deviation 8.5 |
p-value: <0.001t-test, 2 sided
Secondary
Wound Pain
Absolute change from baseline (Week 1) and Week 12 in the Pain Visual Analogue Scale (VAS) Score. The Pain Visual Analogue Scale (VAS) Score is a horizontal line, 100 mm in length, anchored by word descriptors at each end. The subject marked the point on the line that represented his/her perception of his/her current pain status. The Pain Visual Analogue Scale (VAS) Score was determined by measuring in millimeters from the left hand end of the line (no pain) to the point that the subject marked. The Pain Visual Analogue Scale (VAS) Score range 0 (best) to 100 (Worst).
Time frame: 12 weeks
Population: Subjects who received at least 1 dose of SNF472 and had at least 1 postbaseline efficacy measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SNF472 | Wound Pain | -23.6 units on a scale | Standard Deviation 30 |
p-value: 0.015t-test, 2 sided
Secondary
Wound-QoL Global Score
Absolute change from baseline (Week 1) and Week 12 in the Wound-QoL global score. The Wound-QoL questionnaire measures the disease-specific, health related QoL of patients with chronic wounds. It consists of 17 items on impairments that are assessed in retrospect to the preceding 7 days and rated on a 0 (best) to 4 (worse) scale with possible responses from not at all to very much. The total score is the average of the 17 responses.
Time frame: 12 weeks
Population: Subjects who received at least 1 dose of SNF472 and had at least 1 postbaseline efficacy measurement
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SNF472 | Wound-QoL Global Score | -0.9 units on a scale | Standard Deviation 0.87 |
p-value: 0.003t-test, 2 sided