Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
112
Countries
1
Sites
1
Primary Sclerosing Cholangitis (PSC)
The primary objective of this exploratory, indication-finding basket trial is to evaluate and compare the safety and the relationship between the magnitude of Treg responses and clinical responses elicited by low-dose IL-2 therapy in participants with active Pemphigus vulgaris / foliaceus (PV/PF), Mucous Membrane Pemph…
Key facts
- Sponsor
- Universitaetsklinikum Schleswig-Holstein AöR
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 27 Dec 2024 → ongoing
- Decision date (initial)
- 2024-04-04
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Deutsche Forschungsgemeinschaft (DFG)
External identifiers
- EU CT number
- 2023-510297-14-00
- WHO UTN
- U1111-1300-8854
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Safety, Efficacy
The primary objective of this exploratory, indication-finding basket trial is to evaluate and compare the safety and the relationship between the magnitude of Treg responses and clinical responses elicited by low-dose IL-2 therapy in participants with active Pemphigus vulgaris / foliaceus (PV/PF), Mucous Membrane Pemphigoid (MMP), Polymyositis/ Dermatomyositis (PM/DM) and Primary Sclerosing Cholangitis (PSC).
Secondary objectives 1
- Secondary objectives are to estimate the clinical efficacy of low-dose IL-2 therapy assessed by changes in disease-specific measures of disease activity compared to placebo-treated participants.
Conditions and MedDRA coding
Primary Sclerosing Cholangitis (PSC)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10012503 | Dermatomyositis | 100000004858 |
| 20.0 | LLT | 10057069 | Pemphigus foliaceus | 10040785 |
| 20.0 | LLT | 10052802 | Pemphigus vulgaris | 10040785 |
| 20.0 | PT | 10036102 | Polymyositis | 100000004859 |
| 25.0 | PT | 10087064 | Mucous membrane pemphigoid | 100000004858 |
| 20.1 | LLT | 10036732 | Primary sclerosing cholangitis | 10019805 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Single-center, randomized, double-blind and placebo-controlled phase 2 clinical basket trial IL-2-ID is an interdisciplinary, investigator-initiated, randomized, double-blind and placebo-controlled phase 2, proof-of concept, indication-finding basket trial aiming to explore and compare the safety, clinical efficacy, biological responses and the relationship between biological and clinical efficacy of low-dose IL-2 therapy with aldesleukin versus placebo in participants with active Pemphigus vulgaris / foliaceus (PV/PF), Mucous Membrane Pemphigoid (MMP), Polymyositis/ Dermatomyositis (PM/DM) and Primary Sclerosing Cholangitis (PSC).
|
Randomised Controlled | Double | [{"id":103458,"code":2,"name":"Investigator"},{"id":103459,"code":1,"name":"Subject"}] | Low-dose interleukin-2 (aldesleukin): The therapeutic regimen consists of one treatment cycle with daily subcutaneous injections of 1.5 million IU of aldesleukin or placebo for five consecutive days (induction period) followed by seven weekly subcutaneous injections of either 1.5 million IU of aldesleukin or placebo (maintenance period) until the End-of-Treatment (EOT) visit at day 57 (+/- 1). Placebo (Glucose 5%): The therapeutic regimen consists of one treatment cycle with daily subcutaneous injections of 1.5 million IU of aldesleukin or placebo for five consecutive days (induction period) followed by seven weekly subcutaneous injections of either 1.5 million IU of aldesleukin or placebo (maintenance period) until the End-of-Treatment (EOT) visit at day 57 (+/- 1). |
Regulatory references
- Plan to share IPD
- Yes
- IPD plan description
- Will be provided at a later time point.
| EU CT number | Title | Sponsor |
|---|---|---|
| 2013-001599-40 | Evaluation of the safety, tolerability, efficacy and immunological responses of the interleukin-2 analogue Aldesleukin (Proleukin®) in the treatment of systemic lupus erythematosus as prototypic autoimmune disease (PRO-IMMUN). A COMBINED PHASE I/IIA, PROSPECTIVE, OPEN-LABEL AND UNCONTROLLED SINGLE-CENTER STUDY TO ANALYSE SAFETY, TOLERABILITY, EFFICACY AND IMMUNOLOGICAL RESPONSES OF LOW-DOSE SUBCUTANEOUS INTERLEUKIN-2 (ALDESLEUKIN, PROLEUKIN®) IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND INCREASED DISEASE ACTIVITY REFRACTORY TO STANDARD THERAPIES. , Sicherheit, Verträglichkeit, Wirksamkeit und immunologische Effekte des Interleukin-2 Analogs Aldesleukin (Proleukin®) in der Behandlung des Systemischen Lupus Erythematodes als prototypische Autoimmunerkrankung (PRO-IMMUN). EINE KOMBINIERTE PHASE I/IIA, PROSPEKTIVE, OFFENE UND NICHT-KONTROLLIERTE MONO-ZENTRISCHE STUDIE ZUR ANALYSE DER SICHERHEIT, VERTRÄGLICHKEIT, WIRKSAMKEIT UND DER IMMUNOLOGISCHEN EFFEKTE VON NIEDRIG-DOSIERTEM, SUBKUTAN VERABREICHTEN INTERLEUKIN-2 (ALDESLEUKIN, PROLEUKIN®) BEI PATIENTEN MIT SYSTEMISCHEN LUPUS ERYTHEMATODES UND ERHÖHTER KRANKHEITSAKTIVITÄT UNTER STANDARDTHERAPIE., Sicherheit, Verträglichkeit, Wirksamkeit und immunologische Effekte des Interleukin-2 Analogs Aldesleukin (Proleukin®) in der Behandlung des Systemischen Lupus Erythematodes als prototypische Autoimmunerkrankung (PRO-IMMUN). EINE KOMBINIERTE PHASE I/IIA, PROSPEKTIVE, OFFENE UND NICHT-KONTROLLIERTE MONO-ZENTRISCHE STUDIE ZUR ANALYSE DER SICHERHEIT, VERTRÄGLICHKEIT, WIRKSAMKEIT UND DER IMMUNOLOGISCHEN EFFEKTE VON NIEDRIG-DOSIERTEM, SUBKUTAN VERABREICHTEN INTERLEUKIN-2 (ALDESLEUKIN, PROLEUKIN®) BEI PATIENTEN MIT SYSTEMISCHEN LUPUS ERYTHEMATODES UND ERHÖHTER KRANKHEITSAKTIVITÄT UNTER STANDARDTHERAPIE., Sicherheit, Verträglichkeit, Wirksamkeit und immunologische Effekte des Interleukin-2 Analogs Aldesleukin (Proleukin®) in der Behandlung des Systemischen Lupus Erythematodes als prototypische Autoimmunerkrankung (PRO-IMMUN). EINE KOMBINIERTE PHASE I/IIA, PROSPEKTIVE, OFFENE UND NICHT-KONTROLLIERTE MONO-ZENTRISCHE STUDIE ZUR ANALYSE DER SICHERHEIT, VERTRÄGLICHKEIT, WIRKSAMKEIT UND DER IMMUNOLOGISCHEN EFFEKTE VON NIEDRIG-DOSIERTEM, SUBKUTAN VERABREICHTEN INTERLEUKIN-2 (ALDESLEUKIN, PROLEUKIN®) BEI PATIENTEN MIT SYSTEMISCHEN LUPUS ERYTHEMATODES UND ERHÖHTER KRANKHEITSAKTIVITÄT UNTER STANDARDTHERAPIE. | |
| 2016-000488-17 | A Phase II, multi-centre, randomized, double blind, placebo-controlled study to evaluate the efficacy, safety and pharmacokinetics of ILT-101 in patients with active moderate to severe systemic lupus erythematosus (SLE), Estudio multicentrico en fase II, aleatorizado, doble ciego y controlado con placebo para evaluar la eficacia, la seguridad y la farmacocinetica de ILT-101 en pacientes con lupus eritematoso sistemico (LES) activo moderado a grave, Фаза II, многоцентрово, рандомизирано, двойно-сляпо, контролирано с плацебо изпитване за оценка на ефикасността, безопасността и фармакокинетиката на ILT-101 при пациенти с активен умерен до тежък системен лупус еритематозус (СЛЕ), Фаза II, многоцентрово, рандомизирано, двойно-сляпо, контролирано с плацебо изпитване за оценка на ефикасността, безопасността и фармакокинетиката на ILT-101 при пациенти с активен умерен до тежък системен лупус еритематозус (СЛЕ), Фаза II, многоцентрово, рандомизирано, двойно-сляпо, контролирано с плацебо изпитване за оценка на ефикасността, безопасността и фармакокинетиката на ILT-101 при пациенти с активен умерен до тежък системен лупус еритематозус (СЛЕ), A Phase II, multi-centre, randomized, double blind, placebo-controlled study to evaluate the efficacy, safety and pharmacokinetics of ILT-101 in patients with active moderate to severe systemic lupus erythematosus (SLE) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Participants with pemphigus vulgaris / foliaceus (PV/PF) and having mild to moderate disease activity as defined by a PDAI ≥ 6 and ≤ 45.
- Participants with mucous membrane pemphigoid (MMP) and having mild to moderate disease activity as defined by a MMPDAI of ≥ 6 and ≤ 45.
- Participants with polymyositis (PM) or dermatomyositis (DM) and having elevated plasma concentrations of the creatine kinase (CK) of ≥ 300 U/L and ≤ 3000 U/L. Concomitant diagnoses of other rheumatic diseases (overlaps) are allowed.
- Participants with primary sclerosing cholangitis (PSC) and having elevated plasma concentrations of the alkaline phosphatase (AP) of ≥ 1.5 times above the upper limit of normal. Concomitant diagnosis of inflammatory bowel diseases is allowed.
- Age of participants: ≥ 18 years and ≤ 80 years.
Exclusion criteria 2
- Severe impairment of vital organ or life-threatening disease
- Chronically active infectious diseases
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- The IL-2 induced Treg response, defined as the increase in absolute numbers of CD3+CD4+FoxP3+CD127loCD25hi Treg according to the area under the curve (AUC) obtained between day 1 and day 57,
- The clinical response at day 57 assessed by absolute changes in disease-specific and z-standardized disease activity measures from day 1 to day 57. The respective disease activity measures for each of the investigated diseases are the Pemphigus Disease Area Index (PDAI), Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), plasma levels of Creatine-Kinase (CK) or Alkaline Phosphatase (AP).
Secondary endpoints 1
- The clinical response at day 57, assessed by absolute and relative changes in disease-specific measures (PDAI, MMPDAI, CK, AP) between day 1 and day 57 compared with placebo.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PROLEUKIN® S 18 x 106 IE Pulver zur Herstellung einer Injektionslösung oder Infusionslösung
PRD7367018 · Product
- Active substance
- Aldesleukin
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 1500000 IU international unit(s)
- Max total dose
- 18000000 IU international unit(s)
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- L03AC01 — ALDESLEUKIN
- Marketing authorisation
- 17152.00.00
- MA holder
- CLINIGEN HEALTHCARE B.V.
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/22/2578
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- 12 times lower single doses (single doses of 1.5 Mio IU) as in the marketing authorisation for subcutaneous injections will be used diluted as described in the IB.
Placebo 1
SUB13981MIG · Substance
- Active substance
- Glucose
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 10 ml millilitre(s)
- Max total dose
- 1000 ml millilitre(s)
- Max treatment duration
- 8 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitaetsklinikum Schleswig-Holstein AöR
- Sponsor organisation
- Universitaetsklinikum Schleswig-Holstein AöR
- Address
- Haus D6, Ratzeburger Allee 160 Ratzeburger Allee 160
- City
- Luebeck
- Postcode
- 23538
- Country
- Germany
Scientific contact point
- Organisation
- Universitaetsklinikum Schleswig-Holstein AöR
- Contact name
- PD Dr. Jens Humrich
Public contact point
- Organisation
- Universitaetsklinikum Schleswig-Holstein AöR
- Contact name
- PD Dr. Jens Humrich
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruiting | 112 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2024-12-27 | 2025-01-21 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 6 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_UKSH | 2 |
| Subject information and informed consent form (for publication) | Annex 3_Zusammenfassung der Studie Deutsch_2023-510297-14 | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main Study_GER_Redacted | 1.1 |
| Subject information and informed consent form (for publication) | L2_SIS and ICF_Accessory Biological Sampling_GER_Redacted | 1 |
| Subject information and informed consent form (for publication) | L3_SIS and ICF_Skin Biopsy_GER | 1 |
| Subject information and informed consent form (for publication) | L4_Information Leaflet_GER | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-01-26 | Germany | Acceptable 2024-04-03
|
2024-04-04 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-01-15 | Germany | Acceptable 2024-04-03
|
2025-01-15 |