Reduction of SystemiC Inflammation after ischemic stroke by intravenous DNase administration (ReSCInD)

2024-516701-22-00 Protocol RESCIND-1-2023 Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 5 sites · Protocol RESCIND-1-2023

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 36
Countries 1
Sites 5

Reduction of SystemiC Inflammation after ischemic stroke by intravenous DNase administration

To test the hypothesis that DNase 1 administration leads to a reduction of systemic immune response as measured by blood interleukin-1 beta concentration at 24±6 hours after symptom onset (primary end point) in patients after acute ischemic stroke compared with control treatment.

Key facts

Sponsor
Klinikum der Universitaet Muenchen AöR
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Decision date (initial)
2024-10-31
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Else Kröner-Fresenius Stiftung

External identifiers

EU CT number
2024-516701-22-00
EudraCT number
2022-003410-37
ClinicalTrials.gov
NCT05880524

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To test the hypothesis that DNase 1 administration leads to a reduction of systemic immune response as measured by blood interleukin-1 beta concentration at 24±6 hours after symptom onset (primary end point) in patients after acute ischemic stroke compared with control treatment.

Secondary objectives 1

  1. To test the hypothesis that DNase 1 treatment leads to a reduction in post-stroke infections, improves functional outcome (NIHSS, mRS) of stroke patients, and results in positive changes in immunological parameters without compromising patient safety.

Conditions and MedDRA coding

Reduction of SystemiC Inflammation after ischemic stroke by intravenous DNase administration

VersionLevelCodeTermSystem organ class
22.1 PT 10061256 Ischaemic stroke 100000004852

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

  1. - Patients with urgent suspected acute ischemic stroke with symptom onset (last-seen-well) to investigational drug application of less than 12 hours - Consent to participate in the study - Age ≥ 18 years - NIHSS ≥10 at admission

Exclusion criteria 1

  1. - Presence of any of the following: Sinus or cerebral venous thrombosis, intracerebral hemorrhage, subarachnoid hemorrhage on qualifying imaging (cCT with CT-A or MRI with MR-A). However, petechial hemorrhagic transformation of index infarct and cerebral microhemorrhage may be included. - Active malignant tumor disease in the past 6 months. - Current known immunosuppression due to immunomodulatory medication with immunosuppressive dose or underlying immunosuppressive disease (e.g., HIV) - Acute fulminant infectious disease in the last 7 days (fever > 38.5°C or suspected by investigator) - Breastfeeding or pregnant woman, women of childbearing age (under 55 years) without known contraceptive use with positive urine or serum beta-human choriogonadotropin tests - Ischemic stroke or myocardial infarction in the previous 30 days - Surgery in the previous 30 days, except minor dermatologic, urologic, oral surgery, or gynecologic surgery without anesthesia and wound healing problems, and patients with thrombectomy - Estimated or known weight > 100 kg - Known allergies or intolerance to dornase alfa (Pulmozyme) or recombinant protein products derived from Chinese hamster ovary cells - Thrombocytopenia, leukocyte count <1500/μl - Known participation in another clinical trial investigating a drug and/ or medical device in the 7 days prior to study enrollment - Severe renal insufficiency with GFR≤29 ml/min/ 1.73m3 and/or renal insufficiency requiring dialysis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary endpoint, IL-1 β concentration in the blood within 24±6 hrs after symptom onset, will be analyzed in the full analysis set, which comes as close as possible to the IIT principle. A mixed linear regression model is calculated with the IL-1 β value (at 24±6hrs & 3 d) as the dependent variable, the randomized group, the IL-1 β value at baseline & the time point, the interaction of time + group, as independent variables and the patient as a random effect.

Secondary endpoints 1

  1. All secondary endpoints are analyzed descriptively, and differences between the two study arms are explored according to their level of measurement.

Investigational products

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

Test 1

Pulmozyme 2.500 E./2,5 ml, Lösung für einen Vernebler

PRD365105 · Product

Active substance
Dornase Alfa
Pharmaceutical form
NEBULISER SOLUTION
Route of administration
INTRAVENOUS BOLUS USE
Max daily dose
100 mg milligram(s)
Max total dose
100 mg milligram(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
R05CB13 — DORNASE ALFA (DESOXYRIBONUCLEASE)
Marketing authorisation
30289.00.00
MA holder
ROCHE PHARMA AG
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Nebuliser solution used for intravenous injection

Placebo 1

Isotonische Kochsalzlösung

PRD2503464 · Product

Active substance
Sodium Chloride
Substance synonyms
SODIUM CHLORID
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS USE
Max daily dose
100 ml millilitre(s)
Max total dose
100 ml millilitre(s)
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
B05BB01 — ELECTROLYTES
Marketing authorisation
6948822.00.00
MA holder
FRESENIUS KABI DEUTSCHLAND GMBH
MA country
Germany
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum der Universitaet Muenchen AöR

14 Total trials 5 Recruiting 7 Ended
Academic / Non-commercial
Sponsor organisation
Klinikum der Universitaet Muenchen AöR
Address
Feodor-Lynen-Strasse 17, Hadern Hadern
City
Munich
Postcode
81377
Country
Germany

Scientific contact point

Organisation
Klinikum der Universitaet Muenchen AöR
Contact name
Arthur Liesz

Public contact point

Organisation
Klinikum der Universitaet Muenchen AöR
Contact name
Arthur Liesz

Third parties 2

OrganisationCity, countryDuties
Charite Universitaetsmedizin Berlin KöR
ORG-100008480
 Berlin, Germany On site monitoring
University Medical Center Hamburg-Eppendorf
ORG-100008810
 Hamburg, Germany Code 12, Data management

Locations

1 EU/EEA country · 5 investigational sites

By country

CountryMS statusPlanned subjectsSites
Germany Authorised, recruitment pending 36 5
Rest of world — 0 —

Investigational sites

Germany

5 sites · Authorised, recruitment pending
University Medical Center Hamburg-Eppendorf
Neurology, Martinistrasse 52, Eppendorf, Hamburg
Charite Universitaetsmedizin Berlin KöR
Neurology, Hindenburgdamm 30, Lichterfelde, Berlin
Klinikum der Universitaet Muenchen AöR
Institute for Stroke and Dementia Research, Feodor-Lynen-Strasse 17, Hadern, Munich
Medizinische Hochschule Hannover
Neurology, Carl-Neuberg-Strasse 1, Gross Buchholz, Hanover
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
Neurology, Ismaninger Strasse 22, Au-Haidhausen, Munich

Results and documents

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

Documents 13 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-516701-22-00_FP 4
Recruitment arrangements (for publication) K1_Recrutiment arrangements_Placeholder 1
Subject information and informed consent form (for publication) L1_Information to Follow-up Physician_2024-516701-22-00_FP 1.3
Subject information and informed consent form (for publication) L1_SIS and ICF for Follow-Up of pregnancy_2024-516701-22-00_FP 1.3
Subject information and informed consent form (for publication) L1_SIS and ICF_authorised person or legal guardian_2024-516701-22-00_FP 1.4
Subject information and informed consent form (for publication) L1_SIS and ICF_Independent Physician_2024-516701-22-00_FP 1.4
Subject information and informed consent form (for publication) L1_SIS and ICF_Subjects capable of giving consent_2024-516701-22-00_FP 1.4
Subject information and informed consent form (for publication) L1_SIS and ICF_Subjects recovered to be informed and give constent_2024-516701-22-00_FP 1.4
Subject information and informed consent form (for publication) L2_Patient Card_2024-516701-22-00_FP 2
Subject information and informed consent form (for publication) L2_Patients CoR_Copy ICF_Insurance_2024-516701-22-00_FP 1.2
Summary of Product Characteristics (SmPC) (for publication) G2_Pharmacy Manual IMPs_clean_2024-516701-22-00 1.3
Summary of Product Characteristics (SmPC) (for publication) G2_SMPC Pulmozyme_Roche_042017 1
Synopsis of the protocol (for publication) D1_Protocol Synopsis_2024-516701-22-00_not applicable 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-10-11 Germany Acceptable
2024-10-30
 2024-10-31
2 SUBSTANTIAL MODIFICATION SM-1 2025-01-31 Germany Acceptable
2025-03-06
 2025-03-07
3 SUBSTANTIAL MODIFICATION SM-4 2025-05-06 Germany Acceptable
2025-06-03
 2025-06-04
4 SUBSTANTIAL MODIFICATION SM-5 2026-01-21 Germany Acceptable 2026-01-30
5 SUBSTANTIAL MODIFICATION SM-6 2026-03-26 Germany Acceptable
2026-04-20
 2026-04-21
6 NON SUBSTANTIAL MODIFICATION NSM-1 2026-04-23 Germany Acceptable
2026-04-20
 2026-04-23

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