Treatment of Keratolytic Winter Erythema in adults with systemic nitroxoline

2022-501726-38-00 Protocol 1.0 Therapeutic exploratory (Phase II) Ended

Start 30 Jun 2023 · End 19 Jul 2024 · Status Ended · 1 EU/EEA countries · 1 sites · Protocol 1.0

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ended
Participants planned 12
Countries 1
Sites 1

Keratolytic Winter Erythema

Determine the effectiveness of per os Nitroxoline treatment on total skin area affected by KWE over a 22 week time period

Key facts

Sponsor
Oslo University Hospital Hf, Oslo University Hospital Hf
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Skin and Connective Tissue Diseases [C17]
Trial duration
30 Jun 2023 → 19 Jul 2024
Decision date (initial)
2022-11-10
Transition trial
No
Low-intervention
No
Rare-disease indication
Yes
Vulnerable population
No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

Determine the effectiveness of per os Nitroxoline treatment on total skin area affected by KWE over a 22 week time period

Secondary objectives 11

  1. Determine the effectiveness of per os nitroxoline treatment on KWE skin area affection after 22 weeks treatment compared to baseline
  2. Determine the temporal effectiveness of per os nitroxoline treatment on KWE skin area affection
  3. Determine the effectiveness of per os nitroxoline treatment on erythema caused by KWE
  4. Determine the effectiveness of per os nitroxoline treatment on skin desquamation caused by KWE
  5. Determine the effect of per os nitroxoline treatment on water intolerability caused by KWE
  6. Determine the effect of per os nitroxoline treatment on hyperhidrosis caused by KWE
  7. Determine the effect of per os nitroxoline treatment on KWE mediated pain
  8. Determine the effect of per os nitroxoline treatment on KWE mediated itch
  9. Determine the effect of per os nitroxoline treatment on the quality of life of patients with KWE
  10. Determine the effect of per os nitroxoline treatment on skin inflammation and structure
  11. Determine the safety of 750 mg oral nitroxoline per day for 26 weeks in patients with KWE

Conditions and MedDRA coding

Keratolytic Winter Erythema

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Participant have the diagnosis of KWE (typical clinical features confirmed by genetic testing of the patient or a first degree relative)
  2. Participant is ≥ 18 years of age
  3. Body weight is ≥ 50 kg
  4. Fertile women must use effective contraception during the entire study period as defined in Appendix 4
  5. The participant must be capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion criteria 11

  1. Known allergy or intolerance to nitroxoline
  2. Hypersensitivity to any ingredients in the placebo capsule
  3. Known allergy or intolerance to any other ingredients in Nitroxolin Forte capsules (see SPC), in particular soy protein or Ponceau 4R (E124)
  4. Chronic renal failure stage 3b-5 (estimated glomerular filtration rate <45 mL/min/1,73m2)
  5. Abnormal liver test values of ALAT, ASAT or γ-GT >3 × above upper limit of normal (ULN), total bilirubin >2 × ULN or spontaneous INR >1.5
  6. Known unstable or progressive liver disease (e.g., liver cirrhosis, fatty liver, active hepatitis)
  7. The participant is pregnant
  8. The participant is breastfeeding
  9. The participant has a thrombocyte level below 100 x 109 per liter
  10. The participant must use other medication(s) incompatible with the simultaneous use of nitroxoline (including warfarin and other vitamin K-antagonists)
  11. Any condition that in the view of the investigator would suggest that the patient is unable to comply with the study protocol and procedures

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Relative change from baseline of area (% of cm2) affected by KWE (BSA) during the intervention period compared to that of the placebo period

Secondary endpoints 17

  1. Total area measured during the intervention period compared to that of the placebo period (area under the curve)
  2. Time (weeks) to 25%, 50%, 75%, 90% and 100% improvement of area affected by KWE (BSA)
  3. Change from baseline in erythema intensity (graded 0-4) caused by KWE during the intervention period compared to that of the placebo period
  4. Change from baseline in desquamation grade caused by KWE during the intervention period compared to that of the placebo period
  5. Visual analog scale (VAS) of water intolerability during the intervention period to that of the placebo period
  6. Visual analog scale (VAS) of hyperhidrosis during the intervention period to that of the placebo period
  7. Visual analog scale (VAS) of pain during the intervention period to that of the placebo period
  8. Mean visual analog scale (VAS) of itch during the intervention period to that of the placebo period
  9. Histologic analysis of skin biopsies obtained at baseline, week 26 and week 52
  10. DLQI scoring every visit during the intervention period compared to that of the placebo period (quality of life)
  11. SF-36v2®Health Survey at week 26 and 52 compared to baseline (quality of life)
  12. Chalder Fatigue Scale at week 26 and 52 compared to baseline (quality of life)
  13. Hospital Anxiety & Depression Scale at week 26 and 52 compared to baseline (quality of life)
  14. Adverse events due to study intervention (safety)
  15. Abnormalities in physical examination (safety)
  16. Abnormalities in laboratory investigations (safety)
  17. The compliance of capsule administration will be accounted for. The number of remaining capsules for each participant will be counted at every study control visit.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

—

SCP18755880 · ATC

Route of administration
ORAL USE
Max daily dose
750 mg milligram(s)
Max total dose
136.5 g gram(s)
Max treatment duration
26 Week(s)
Authorisation status
Authorised
ATC code
J01XX07 — NITROXOLINE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Capsules identical to Nitroxolin Forte 250 mg capusules.

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital Hf

73 Total trials 37 Recruiting 25 Ended
Academic / Non-commercial
Sponsor organisation
Oslo University Hospital Hf
Address
Taarnbygget, Kirkeveien 166 Kirkeveien 166
City
Oslo
Postcode
0450
Country
Norway

Scientific contact point

Organisation
Oslo University Hospital Hf
Contact name
Øystein Sandanger

Public contact point

Organisation
Oslo University Hospital Hf
Contact name
Øystein Sandanger

Oslo University Hospital Hf

73 Total trials 37 Recruiting 25 Ended
Academic / Non-commercial
Sponsor organisation
Oslo University Hospital Hf
Address
Taarnbygget, Kirkeveien 166 Kirkeveien 166
City
Oslo
Postcode
0450
Country
Norway

Scientific contact point

Organisation
Oslo University Hospital Hf
Contact name
Øystein Sandanger

Public contact point

Organisation
Oslo University Hospital Hf
Contact name
Øystein Sandanger

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Norway Ended 12 1
Rest of world — 0 —

Investigational sites

Norway

1 site · Ended
Oslo University Hospital Hf
Section of dermatology, Sognsvannsveien 20, 0372, Oslo

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Norway 2023-06-30 2024-07-19 2023-07-31 2024-02-01

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

TitleSubmission dateStatusType
Results
SUM-79361
 2025-04-16T12:40:48 Submitted Summary of Results

Documents 1 file

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Summary of results (for publication) Summary of results 1

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2022-08-26 Norway Acceptable
2022-11-10
 2022-11-10
2 NON SUBSTANTIAL MODIFICATION NSM-1 2023-06-26 Norway Acceptable
2022-11-10
 2023-06-26