Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
64
Countries
2
Sites
17
Tuberous sclerosis complex (TSC)
Neuropsychologic outcome at 24 months of age assessed by rater blinded neuropsychologic testing measured by the cognitive scale on the Bayley Scales of Infant and Toddler Development III (BSID-III) compared with Standard of Care (SOC) alone.
Key facts
- Sponsor
- Heidelberg University Hospital AöR
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 15 Nov 2023 → ongoing
- Decision date (initial)
- 2025-03-17
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- BMFTR · Pfizer
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Therapy, Safety
Neuropsychologic outcome at 24 months of age assessed by rater blinded neuropsychologic testing measured by the cognitive scale on the Bayley Scales of Infant and Toddler Development III (BSID-III)
compared with Standard of Care (SOC) alone.
Secondary objectives 12
- Neuropsychologic outcome at 12 months of age assessed by rater blinded neuropsychologic testing using the cognitive scale on the BSID-III in both groups. Cognitive impairment will be defined as BSID-III cognitive scale score <70 similar to the EPISTOP trial.
- Adaptive behaviour assessed by the Vineland Adaptive Behaviour Scales (VABS-3; digital) at the age of 12 months and 24 months.
- Evidence for autism spectrum disorder measured at 12 months and 24 months of age by the Autism Diagnostic Observation Schedule (ADOS-2). Suspicion of autism spectrum disorder will be defined as ADOS >12, similar to the EPISTOP trial.
- Evidence for autism spectrum disorder measured by the Modified Checklist for Autism in Toddlers revised (M-CHAT-R/F).
- TSC-associated Neuropsychiatric Disorders (TAND) severity assessed by the TAND-L Checklist (German version) at 12 and 24 months
- Assessment of seizure frequency and the occurrence/severity of infantile spasms (IS) measured by seizure diaries, care giver questionnaires and electroencephalogram (EEG) recordings
- Reduction of number and size of cardiac rhabdomyoma and arrhythmia (if present).
- Reduction of cerebral tumor number and size on cranial magnetic resonance imaging (cMRI) (if present)
- Adverse events (AE), serious adverse events (SAE) and Adverse Events of Special Interest (AESI), assessed by the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0, or most recent version).
- Assessment of safety laboratory data and vital signs
- Assessment of EEG recordings for the occurrence of hypsarrhythmia and epileptiform discharges.
- Renal changes in abdominal sonography: Volume and size of angiomyolipomas (if present), kidney size, renal pelvis dilation, echogenicity.
Conditions and MedDRA coding
Tuberous sclerosis complex (TSC)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10045138 | Tuberous sclerosis | 10010331 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Standard of Care + Sirolimus Pal formulation: 1 mg/ml oral solution; Routes of administration: oral; Dosage: Sirolimus will be administered as oral solution adapted to body surface area with a starting dose of 0.5 mg/m2/day (0- <1 months of age) to
0.9 mg/m2/day (3- <4 months of age) divided BID (twice daily) until 2 years of age. Sirolimus 12h trough levels will be measured at every study visit and doses titrated and adapted to reach target trough levels of 5-10 ng/ml.
|
Randomised Controlled | None | ||
| 2 | Standard of Care Treatment duration: starting within the first 4 months of life and continued until
the 2nd birthday.
|
Randomised Controlled | None |
Regulatory references
- Scientific advice from competent authorities
- Federal Institute For Drugs And Medical Devices
- Plan to share IPD
- Yes
- IPD plan description
- Please refer to section 14.4 Declaration regarding Data Sharing in the protocol.
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Definite diagnosis of TSC according to the 2021 Updated International Tuberous Sclerosis Complex Diagnostic Criteria
- <4 months of age at the time of enrolment (randomization and treatment initiation must occur before 4 months of age; infants born prematurely must have a corrected age of at least 39 weeks, calculated by subtracting the number of weeks born before 40 weeks gestation from the actual chronological age, in weeks)
- Signed informed consent from legal guardian(s) prior to any study specific procedure.
Exclusion criteria 7
- Has a TSC-associated condition for which mTOR treatment is clinically indicated, i.e. subependymal giant cell astrocytoma (SEGA).
- Has been treated in the past or is currently being treated at the time of enrolment with systemic mTOR inhibitors (such as rapamycin, sirolimus, or everolimus)
- Contraindication to study medication. Rapamune® oral solution contains soya oil. Patients allergic to peanut or soya must not take this medicine
- Current enrolment, or observation period of competing clinical trials at any time during enrolment in the study.
- History of significant prematurity, defined as gestational age < 30 weeks at the time of delivery, or other significant medical complications at birth or during the neonatal period that, apart from TSC, would convey additional risk of seizures or neurodevelopmental delay (i.e. hypoxic ischemic encephalopathy (HIE), severe neonatal infection, major surgery, prolonged ventilatory or other lifesaving supportive care or procedures)
- Abnormal laboratory values at screening (i.e., renal function, liver function, or bone marrow production) that are in the opinion of the investigator clinically significant and may jeopardize the safety of the study subject.
- Parents / caregiver of the child who are, in the opinion of the investigator, unable to comply with the requirements of the study
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Neuropsychologic outcome at 24 months of age assessed by rater blinded neuropsychologic testing measured by the cognitive scale on the Bayley Scales of Infant and Toddler Development III (BSID-III) compared with Standard of Care (SOC) alone.
Secondary endpoints 12
- Neuropsychologic outcome at 12 months of age assessed by rater blinded neuropsychologic testing using the cognitive scale on the BSID-III in both groups. Cognitive impairment will be defined as BSID-III cognitive scale score <70 similar to the EPISTOP trial.
- Adaptive behaviour assessed by the Vineland Adaptive Behaviour Scales (VABS-3; digital) at the age of 12 months and 24 months.
- Evidence for autism spectrum disorder measured at 12 months and 24 months of age by the Autism Diagnostic Observation Schedule (ADOS-2). Suspicion of autism spectrum disorder will be defined as ADOS >12, similar to the EPISTOP trial.
- Evidence for autism spectrum disorder measured by the Modified Checklist for Autism in Toddlers revised (M-CHAT-R/F).
- TSC-associated Neuropsychiatric Disorders (TAND) severity assessed by the TAND-L Checklist (German version) at 12 and 24 months.
- Assessment of seizure frequency and the occurrence/severity of infantile spasms (IS) measured by seizure diaries, care giver questionnaires and electroencephalogram (EEG) recordings.
- Reduction of number and size of cardiac rhabdomyoma and arrhythmia (if present).
- Reduction of cerebral tumor number and size on cranial magnetic resonance imaging (cMRI) (if present)
- Adverse events (AE), serious adverse events (SAE) and Adverse Events of Special Interest (AESI), assessed by the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0, or most recent version).
- Assessment of laboratory data and vital signs.
- Assessment of EEG recordings for the occurrence of hypsarrhythmia and epileptiform discharges.
- Renal changes in abdominal sonography: Volume and size of angiomyolipomas (if present), kidney size, renal pelvis dilation, echogenicity.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Rapamune 1 mg/mL oral solution
PRD3342151 · Product
- Active substance
- Sirolimus
- Pharmaceutical form
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 0.9 mg/m2 milligram(s)/sq. meter
- Max total dose
- 657 mg/m2 milligram(s)/square meter
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AA10 — SIROLIMUS
- Marketing authorisation
- EU/1/01/171/001
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 13
SUB10941MIG · Substance
- Active substance
- Tetracosactide
- Pharmaceutical form
- SUSPENSION FOR INJECTION
- Route of administration
- INTRAMUSCULAR INJECTION
- Max daily dose
- 40 IU international unit(s)
- Max total dose
- 280 IU international unit(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB12318MIG · Substance
- Active substance
- Sodium Valproate
- Pharmaceutical form
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 30 mg/kg milligram(s)/kilogram
- Max total dose
- 21600 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09770MIG · Substance
- Active substance
- Phenobarbital
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 5 mg/kg milligram(s)/kilogram
- Max total dose
- 3600 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB06113MIG · Substance
- Active substance
- Carbamazepine
- Pharmaceutical form
- ORAL SUSPENSION
- Route of administration
- ORAL
- Max daily dose
- 35 mg/kg milligram(s)/kilogram
- Max total dose
- 25200 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB04091MIG · Substance
- Active substance
- Propranolol Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- SOLUTION FOR INJECTION
- Max daily dose
- 4 mg/kg milligram(s)/kilogram
- Max total dose
- 2880 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00015MIG · Substance
- Active substance
- Valproic Acid
- Pharmaceutical form
- CAPSULE, PROLONGED RELEASE, HARD
- Route of administration
- ORAL
- Max daily dose
- 4 mg/kg milligram(s)/kilogram
- Max total dose
- 2880 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB03289MIG · Substance
- Active substance
- Midazolam Hydrochloride
- Pharmaceutical form
- OROMUCOSAL SOLUTION
- Route of administration
- BUCCAL USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 14400 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00048MIG · Substance
- Active substance
- Vigabatrin
- Pharmaceutical form
- GRANULES FOR ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 150 mg/kg milligram(s)/kilogram
- Max total dose
- 108000 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB07069MIG · Substance
- Active substance
- Diazepam
- Pharmaceutical form
- RECTAL SOLUTION
- Route of administration
- RECTAL USE
- Max daily dose
- 30 mg milligram(s)
- Max total dose
- 21600 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10119MIG · Substance
- Active substance
- Propranolol
- Pharmaceutical form
- FILM COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 4 mg/kg milligram(s)/kilogram
- Max total dose
- 2880 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09510MIG · Substance
- Active substance
- Oxcarbazepine
- Pharmaceutical form
- ORAL SUSPENSION
- Route of administration
- ORAL
- Max daily dose
- 35 mg/kg milligram(s)/kilogram
- Max total dose
- 25200 mg/kg milligram(s)/kilogram
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB10018MIG · Substance
- Active substance
- Prednisolone
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 40 mg/kg milligram(s)/kilogram
- Max total dose
- 560 mg/Kg milligram(s)/kilogram
- Max treatment duration
- 2 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB00038MIG · Substance
- Active substance
- Verapamil
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 80 mg milligram(s)
- Max total dose
- 28800 mg milligram(s)
- Max treatment duration
- 24 Month(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
Heidelberg University Hospital AöR
- Sponsor organisation
- Heidelberg University Hospital AöR
- Address
- Im Neuenheimer Feld 672, Neuenheim Neuenheim
- City
- Heidelberg
- Postcode
- 69120
- Country
- Germany
Scientific contact point
- Organisation
- Heidelberg University Hospital AöR
- Contact name
- Sektion für Pädiatrische Epileptologie
Public contact point
- Organisation
- Heidelberg University Hospital AöR
- Contact name
- Sektion für Pädiatrische Epileptologie
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Universitaetsklinikum Heidelberg AöR ORG-100013733
|
Heidelberg, Germany | On site monitoring, Code 10, Code 12, Code 5, Data management, Code 8 |
Locations
2 EU/EEA countries · 17 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruiting | 4 | 1 |
| Germany | Ongoing, recruiting | 60 | 16 |
| Rest of world | — | 0 | — |
Investigational sites
Medical University Of Vienna
Universitätsklinik für Kinder- und Jugendheilkunde, Epilepsie-Monitoring-Unit, Waehringer Guertel 18-20, Alsergrund, Vienna
Universitaetsklinikum Frankfurt AöR
Dpt. of Neuropediatrics, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Klinikum der Universitaet Muenchen AöR
Department of Pediatric Neurology, Lindwurmstrasse 4, Ludwigsvorstadt-Isarvorstadt, Munich
Vestische Kinder Und Jugendklinik Datteln
Department of Neuropediatrics, Developmental Neurology and Social Pediatrics, Dr.-Friedrich-Steiner-Strasse 5, 45711, Datteln
Universitaetsklinikum Bonn AöR
Dpt. of Neuropediatrics, Venusberg-Campus 1, Venusberg, Bonn
Universitaetsklinikum Tuebingen AöR
Neuropediatrics (Dep. III), Hoppe-Seyler-Strasse 1, Nordstadt, Tuebingen
University Medical Center Hamburg-Eppendorf
Klinik und Poliklinik für Kinder- und Jugendmedizin, Martinistrasse 52, Eppendorf, Hamburg
Katholisches Klinikum Bochum gGmbH
Klinik für Kinder- und Jugendmedizin der Ruhr Universität Bochum, Gudrunstrasse 56, Grumme, Bochum
Charite Universitaetsmedizin Berlin KöR
Dpt. of Neuropediatrics, Augustenburger Platz 1, Wedding, Berlin
AMEOS Krankenhausgesellschaft Oberhausen mbH
Klinik für Kinder- und Jugendmedizin, Wilhelmstrasse 34, Sterkrade-Mitte, Oberhausen
Universitaet Leipzig
Department of Pediatric Neurology and Social Pediatrics, Liebigstrasse 20a, Zentrum-Suedost, Leipzig
Medical Center - University Of Freiburg
Center of Pediatrics, Department of Neuropediatrics and Muscle Disorders, Breisacher Strasse 62, Stuehlinger, Freiburg Im Breisgau
Universitaetsklinikum Giessen und Marburg GmbH
Kinderklinik, Abteilung für Kinderneurologie, Rudolf Buchheim Strasse 8, 35392, Giessen
Universitaetsklinikum Muenster AöR
General Paediatrics / Child Neurology, Albert-Schweitzer-Campus 1, Sentrup, Muenster
Universitaetsklinikum Erlangen AöR
Kinder- und Jugendklinik, Abteilung Neuropädiatrie, Loschgestrasse 15, Innenstadt, Erlangen
Universitaetsklinikum Heidelberg AöR
Zentrum für Kinder- und Jugendmedizin, Im Neuenheimer Feld 430, Neuenheim, Heidelberg
Universitaetsklinikum Essen AöR
Klinik für Kinderheilkunde I, Hufelandstrasse 55, Holsterhausen, Essen
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 |
|---|---|---|---|---|---|
| Austria | 2025-07-16 | 2026-01-14 | |||
| Germany | 2023-11-15 | 2024-03-01 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 46 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_PROTECT_public | 7.1 |
| Protocol (for publication) | D2_PROTECT_StudyProtocolSummaryOfChanges | 7 |
| Recruitment arrangements (for publication) | 20230703_list_German_trial_sites_Number_of_participants_V01 | 3 |
| Recruitment arrangements (for publication) | K1_list_German_trial_sites_PI | 1 |
| Recruitment arrangements (for publication) | K1_PROTECT_List Trial sites_AT | 2 |
| Recruitment arrangements (for publication) | K1_PROTECT_Recruitment Arr | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment_Arr_PROTECT_public | 1 |
| Recruitment arrangements (for publication) | K2__Recruitment_Mat_PROTECT_Adv_public | 2 |
| Recruitment arrangements (for publication) | K2_PROTECT_Recruitment_Mat_flyer_AT | 3.1 |
| Subject information and informed consent form (for publication) | D4_PFD_DE_PROTECT_diary_Control | 2 |
| Subject information and informed consent form (for publication) | D4_PFD_DE_PROTECT_diary_Control_en | 2 |
| Subject information and informed consent form (for publication) | D4_PFD_DE_PROTECT_diary_Control_TC | 2 |
| Subject information and informed consent form (for publication) | D4_PFD_DE_PROTECT_diary_Intervention | 2 |
| Subject information and informed consent form (for publication) | D4_PFD_DE_PROTECT_diary_Intervention_en | 2 |
| Subject information and informed consent form (for publication) | D4_PFD_DE_PROTECT_diary_Intervention_TC | 2 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC | 5 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Anlage_I_Zeitplan_ | 4 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Anlage_I_Zeitplan_AT | 5 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Anlage_I_Zeitplan_en | 4 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Anlage_II_Erganzende_Informationen_zu_Rapamune | 5_1 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Anlage_II_Erganzende_Informationen_zu_Rapamune_AT | 5_1 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Anlage_II_Erganzende_Informationen_zu_Rapamune_en | 5 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_AT | 2.2 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Begleitstudie-Impfantwort | 4 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Begleitstudie-Impfantwort_AT | 1.2 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Begleitstudie-Impfantwort_en | 4 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Begleitstudie-Individuelle Pradiktoren | 3 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Begleitstudie-Individuelle Pradiktoren_AT | 1.2 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Begleitstudie-Individuelle Pradiktoren_en | 3 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Begleitstudie-Neuropsychologische Nachbeobachtung | 3_1 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_Begleitstudie-Neuropsychologische Nachbeobachtung_AT | 1.2 |
| Subject information and informed consent form (for publication) | L1_PROTECT_IC_en | 5 |
| Subject information and informed consent form (for publication) | L1_PROTECT_Kontaktdaten_Wien_AT_public | 2 |
| Subject information and informed consent form (for publication) | L2_PROTECT_IC_Begleitstudie-Impfantwort_TC | 4 |
| Subject information and informed consent form (for publication) | L2_PROTECT_IC_Begleitstudie-Individuelle Pradiktoren_TC | 3 |
| Subject information and informed consent form (for publication) | L2_PROTECT_IC_Begleitstudie-Neuropsychologische Nachbeobachtung_TC | 3_1 |
| Subject information and informed consent form (for publication) | Placeholder_revised CTIS transparency rules | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Rapamune | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_Rapamune_202207vs202207_New_Representative_combined_comparison | 3 |
| Summary of Product Characteristics (SmPC) (for publication) | G1_Add_Info_Sirolimus_PROTECT | 4 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2022-502332-39-00_EN_PROTECT_TC | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2022-502332-39-00_ger_DE_PROTECT_TC | 4 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_2022-502332-39-00_Lay_ger_DE_PROTECT_TC | 1 |
| Synopsis of the protocol (for publication) | D1_Synopsis_en_PROTECT | 1 |
| Synopsis of the protocol (for publication) | D1_Synopsis_ger_DE_PROTECT | 5.1 |
| Synopsis of the protocol (for publication) | D1_Synopsis_Lay_ger_DE_PROTECT | 1 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-22 | Germany | Acceptable 2023-09-18
|
2023-09-20 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-02-22 | Germany | Acceptable 2024-03-27
|
2024-03-28 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-10-10 | Germany | Acceptable 2024-11-25
|
2024-11-26 |
| 4 | SUBSEQUENT ADDITION OF MSC | APP-4 | 2024-12-05 | Acceptable 2024-11-25
|
2025-03-17 | |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-08-25 | Germany | Acceptable 2024-11-25
|
2025-08-25 |
| 6 | SUBSTANTIAL MODIFICATION | SM-3 | 2026-03-24 | Acceptable 2026-05-26
|
2026-05-26 |