Proof of concept study to assess the efficacy and safety of Danicopan (factor D inhibitor) in adult patients with chronic spontaneous urticaria resistant to H1-antihistamine treatment (DANICSU).

2024-512386-14-00 Protocol TMP-08012024-3 Therapeutic exploratory (Phase II) Ended

End 20 Oct 2024 · Status Ended · 1 EU/EEA countries · 4 sites · Protocol TMP-08012024-3

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ended
Participants planned 24
Countries 1
Sites 4

Chronic spontaneous urticaria

To assess the role of a complement Factor D inhibitor, Danicopan, by comparing the change in Urticaria Activity Score UAS7 from baseline (week 1, V1) to the end of the open label treatment phase (week 17, V5) in adult CSU patients exhibiting low total IgE (≤40 kU/l) and in patients with high total IgE levels (>40 kU/l…

Key facts

Sponsor
Fraunhofer Institute For Translational Medicine And Pharmacology ITMP
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
completed 20 Oct 2024
Decision date (initial)
2024-09-24
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Alexion Pharmaceuticals, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To assess the role of a complement Factor D inhibitor, Danicopan, by comparing the change in Urticaria Activity Score UAS7 from baseline (week 1, V1) to the end of the open label treatment phase (week 17, V5) in adult CSU patients exhibiting low total IgE (≤40 kU/l) and in patients with high total IgE levels (>40 kU/l).

Secondary objectives 8

  1. To assess the effect of Danicopan treatment on quality of life in patients who exhibit low - (≤40 kU/l) and high (>40 kU/l) total IgE levels
  2. To assess the effect of Danicopan treatment on rate and time to onset of clinically meaningful response (time before the patient experience clinical response for the first time) in patients who exhibit low - (≤40 kU/l) and high (>40 kU/l) total IgE levels
  3. To assess the time of complete response in patients who exhibit low - (≤40 kU/l) and high (>40 kU/l) total IgE levels
  4. To assess the time to non-response (symptoms recurrence after study-drug discontinuation) in patients who exhibit low - (≤40 kU/l) and high (>40 kU/l) total IgE levels
  5. To evaluate the use of rescue medication (oral corticosteroids and/or non-sedating H1-AH), (substance and/or substance class)
  6. To evaluate Pharmacokinetics (PK): Danicopan plasma concentrations pre- and post-dose at visit 1, 3 and 5
  7. To evaluate Pharmacodynamics (PD): a. Serum alternative pathway Wieslab (APW) b. Plasma Bb fragment of complement factor B (Bb) and Factor D at visit 1, 3 and 5
  8. To evaluate the safety of Danicopan in patients with CSU

Conditions and MedDRA coding

Chronic spontaneous urticaria

VersionLevelCodeTermSystem organ class
20.0 PT 10072757 Chronic spontaneous urticaria 100000004858

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Study duration per patient will be 31 (to 32) weeks
The duration of the screening period is up to three weeks, from visit 0 up to visit 1 (day 1 in week 1). The open-label treatment phase starts at week 1 until the end of week 16, followed by a 12-week follow-up phase.
 Not Applicable None

Regulatory references

Plan to share IPD
No
EU CT numberTitleSponsor
2023-508571-37-00 A Phase 2, Double-Masked, Placebo-Controlled, Dose Range Finding Study of Danicopan (ALXN2040) in Patients with Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD) Alexion Pharmaceuticals Inc.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Diagnosis of chronic spontaneous urticaria for >6 months
  2. Patient is ≥ 18 years of age
  3. Patient is diagnosed with moderate to severe CSU which is refractory to standard of care treatment at the time of enrollment, as defined by the following: o presence of itch and hives for ≥6 consecutive weeks at any time prior to enrollment despite concurrent use of H1- antihistamines o Urticaria activity score (UAS7; range 0-42) ≥ 16, in the week prior to stratification (Day 1)
  4. Complete vaccination against Neisseria meningitidis within 3 years prior to, or willingness to receive vaccinations or boosters against each serotype (MenACWY, MenB) as described in chapter 5.6.7 of the study protocol

Exclusion criteria 8

  1. Patients whose urticaria is solely due to inducible urticaria
  2. Hypersensitivity to the active substance or to any of the excipients present in the danicopan formulation
  3. Participants with unresolved N meningitidis infection
  4. History of N. meningitidis infection
  5. Other diseases with symptoms of urticaria or angioedema
  6. Any other skin disease associated with chronic itching that might confound the study evaluations and results
  7. Participation in other clinical trials, specifically with investigational non-biologics within the previous 30 days or reception of biologics and intravitreal treatments in the previous 3 months
  8. Other treatments for CSU (e.g., systemic corticosteroids or other immunosuppressive medication) within specified timelines

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The change in baseline to week 17 in UAS7 for patients exhibiting low total IgE (≤40 kU/L) and patients with high total IgE levels (>40 kU/L).

Secondary endpoints 4

  1. Disease control: Urticaria Control Test (UCT) score and change to baseline; Angioedema Activity Score (AAS), score and change to baseline, percentage of patients with a positive UCT and AAS, respectively
  2. Disease-specific quality of life: Dermatological Quality of Life Index, (DLQI), score and change to baseline; Chronic Urticaria Quality of Life Questionnaire ( CU-Q2oL), score and change to baseline; Angioedema Quality of Life Questionnaire (AE-QoL), score and change to baseline)
  3. Responder rates regarding UAS7 and UCT (none-, partial-, complete response)
  4. Rescue medication use (H1-AH, oral glucocorticoids) (substance and/or substance class)

Investigational products

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

Test 1

Danicopan

SUB189885 · Substance

Active substance
Danicopan
Pharmaceutical form
FILM COATED TABLET
Route of administration
ORAL
Max daily dose
600 mg milligram(s)
Max total dose
52500 mg milligram(s)
Max treatment duration
16 Week(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Auxiliary 2

MenQuadfi solution for injection Meningococcal Group A, C, W and Y conjugate vaccine

PRD8540920 · Product

Active substance
Neisseria Meningitidis, Serogroup C, Polysaccharide, Conjugated to Tetanus Toxoid
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
Max daily dose
0.5 ml millilitre(s)
Max total dose
0.5 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
J07AH08 — -
Marketing authorisation
EU/1/20/1483/001
MA holder
SANOFI PASTEUR
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Bexsero suspension for injection in pre-filled syringe Meningococcal group B Vaccine (rDNA, component, adsorbed)

PRD2149122 · Product

Active substance
Recombinant Neisseria Meningitidis Group B Nhba Fusion Protein Produced in E. Coli Cells by Recombinant DNA Technology Adsorbed on Aluminium Hydroxide
Pharmaceutical form
SUSPENSION FOR INJECTION
Route of administration
SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
Max daily dose
0.5 ml millilitre(s)
Max total dose
1.0 ml millilitre(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
J07AH09 — -
Marketing authorisation
EU/1/12/812/001
MA holder
GSK VACCINES S.R.L.
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fraunhofer Institute For Translational Medicine And Pharmacology ITMP

4 Total trials 3 Recruiting 1 Ended
Academic / Non-commercial
Sponsor organisation
Fraunhofer Institute For Translational Medicine And Pharmacology ITMP
Address
Theodor-Stern-Kai 7, Sachsenhausen Sachsenhausen
City
Frankfurt Am Main
Postcode
60596
Country
Germany

Scientific contact point

Organisation
Fraunhofer Institute For Translational Medicine And Pharmacology ITMP
Contact name
Dr. Melba Munoz Rodan

Public contact point

Organisation
Fraunhofer Institute For Translational Medicine And Pharmacology ITMP
Contact name
Dr. Isabel Dittmann

Third parties 2

OrganisationCity, countryDuties
The University Of Colorado Denver Anschutz Medical Campus
ORG-100031302
 Aurora, United States Laboratory analysis
Aliri USA Inc.
ORG-100052116
 Colorado Springs, United States Laboratory analysis

Locations

1 EU/EEA country · 4 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Ended 24 4
Rest of world — 0 —

Investigational sites

Germany

4 sites · Ended
Charite Universitaetsmedizin Berlin KöR
Institut of Allergology (IFA), Hindenburgdamm 30, Lichterfelde, Berlin
Philipps-Universitaet Marburg
Klinik für Dermatologie und Allergologie, Baldingerstrasse, 35043, Marburg
Universitaetsklinikum Muenster AöR
Klinik für Hautkrankheiten - Allergologie, Von-Esmarch-Strasse 58, Sentrup, Muenster
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Hautklinik und Polikinik / CRC Joha, Langenbeckstrasse 1, Oberstadt, Mainz

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
DANICOPAN Summary of results of the clinical study
SUM-102547
 2025-10-17T10:16:34 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
DANICOPAN Zusammenfassung der Ergebnisse der klinischen Prüfung für Laien 2025-10-17T10:17:06 Submitted Laypersons Summary of Results

Documents 15 files

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

TypeTitleVersion
Laypersons summary of results (for publication) DANICOPAN Zusammenfassung der Ergebnisse der klinischen Prufung fur Laien 1
Protocol (for publication) D1_Protocol 2024-512386-14-00_redacted 2
Protocol (for publication) D4_AAS Germany 1
Protocol (for publication) D4_AE-QoL 1
Protocol (for publication) D4_CU-Q2oL_GermanVersion 1
Protocol (for publication) D4_DLQI_German Version 1
Protocol (for publication) D4_Medication diary 1
Protocol (for publication) D4_UCT 1
Protocol (for publication) D4_Urticaria Patient Diary 1
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF adults 2
Subject information and informed consent form (for publication) L2_Other subject information material Patient Safety Card 1
Summary of results (for publication) DANICOPAN Summary of results of the clinical study 1
Synopsis of the protocol (for publication) D1_Protocol synopsis DE 2024-512386-14-00_clean 2
Synopsis of the protocol (for publication) D1_Protocol synopsis ENG 2024-512386-14-00_clean 2

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-07-31 Germany Acceptable
2024-09-20
 2024-09-24

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