Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - First administration to humans
Status
Ongoing, recruitment ended
Participants planned
69
Countries
7
Sites
18
Frontotemporal Dementia (FTD)
Part A - To investigate the safety and tolerability of single doses of DNL593 in healthy participants Part B - To investigate the safety and tolerability of multiple doses of DNL593 in participants with FTD-GRN. Part C - To investigate the safety and tolerability of multiple doses of DNL593 in participants with FTD-GRN…
Key facts
- Sponsor
- Denali Therapeutics Inc.
- Participant type
- Patients, Healthy volunteers
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 13 Nov 2024 → ongoing
- Decision date (initial)
- 2024-05-24
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Denali Therapeutics Inc & Takeda Pharmaceuticals Ltd - Commercial
External identifiers
- EU CT number
- 2023-508697-28-00
- EudraCT number
- 2021-005733-16
- ClinicalTrials.gov
- NCT05262023
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Pharmacokinetic, Safety, Others
Part A
- To investigate the safety and tolerability of single doses of DNL593 in healthy participants
Part B
- To investigate the safety and tolerability of multiple doses of DNL593 in
participants with FTD-GRN.
Part C
- To investigate the safety and tolerability of multiple doses of DNL593 in
participants with FTD-GRN up to 18 months.
Secondary objectives 1
- Part A: - To characterize the serum PK of DNL593 following single doses in healthy participants - To characterize the concentration of DNL593 in CSF following single doses of DNL593 in healthy participants Part B: - To characterize the serum PK of DNL593 following multiple doses of DNL593 in participants with FTD-GRN. - To characterize the concentration of DNL593 in CSF following multiple doses in participants with FTD-GRN. - To evaluate change in plasma Nfl following multiple doses of DNL594 in participants with FTD-GRN. Part C: - To characterize the serum PK of DNL593 following multiple doses of DNL593 in participants with FTD-GRN. - To characterize the concentration of DNL593 in CSF following multiple doses of DNL593 in participants with FTDGRN.
Conditions and MedDRA coding
Frontotemporal Dementia (FTD)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10068968 | Frontotemporal dementia | 100000004852 |
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Part A Dose Escalation Part A will evaluate the safety, tolerability, PK, and PD of single doses of DNL593 in healthy male and healthy female participants of nonchildbearing potential.
|
Randomised Controlled | Double | [{"id":187721,"code":5,"name":"Carer"},{"id":187722,"code":3,"name":"Monitor"},{"id":187719,"code":1,"name":"Subject"},{"id":187720,"code":2,"name":"Investigator"}] | Invetigational arm: DNL593 (Healthy Participant) Placebo arm: Placebo (Healthy Participant) |
| 2 | Part B Multiple Dose Part B will evaluate the safety, tolerability, PK, and PD of multiple doses of DNL593 in participants with frontotemporal dementia (FTD) over 25 weeks.
|
Randomised Controlled | Double | [{"id":187726,"code":1,"name":"Subject"},{"id":187725,"code":2,"name":"Investigator"},{"id":187724,"code":3,"name":"Monitor"},{"id":187727,"code":5,"name":"Carer"}] | Invetigational arm: DNL593 (Participants with FTD) Placebo arm: Placebo (Participants with FTD) |
| 3 | Part C Optional OLE Part B will be followed by Part C, an optional 18-month OLE period available for all participants who complete Part B.
|
Not Applicable | None | Participants from Cohort B1: DNL593 (Participants with FTD) Participants from Cohort B2: DNL593 (Participants with FTD) Participants from Cohort B3: DNL593 (Participants with FTD) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Part A: - Women of non-childbearing potential (surgically sterilized or post menopausal) or men, aged ≥18 to ≤ 55 years - BMI of ≥ 18 to ≤ 32 kg/m² - When engaging in sex with a woman of child bearing potential, both the male participant and his female partner must use highly effective contraception Part B: - Women of non-childbearing potential (surgically sterilized or post menopausal) or men, aged ≥18 to ≤ 80 years. Women who are of childbearing potential but on highly effective, low user dependent contraceptive methods will be allowed. - BMI of ≥ 18 to ≤ 32 kg/m² - Have a Clinical Dementia Rating® plus National Alzheimer's Coordinating Center frontotemporal lobar degeneration global score ≥ 0.5 - Have confirmed granulin (GRN) mutation via genetic testing or historical records available for review by investigator - When engaging in sex with a woman of child bearing potential, both the male participant and his female partner must use highly effective contraception Part C: All participants who completed Part B of this trial are eligible for an 18-month OLE if the participant has no unresolved clinically significant TEAEs, where continued dosing may represent a risk to participant safety.
Exclusion criteria 1
- • Have any history of clinically significant neurologic, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematologic, immunologic, or allergic disease, or other major disorders • Have a history of malignancy, except fully resected basal cell carcinoma or other malignancies at low risk of recurrence • Have a clinically significant history of stroke, cognitive impairment due to causes other than FTD, seizure within 5 years of screening, or head trauma with loss of consciousness within 2 years of screening • Have a positive serum pregnancy test or are currently lactating or breastfeeding
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs) [Timeframe: Up to 18 months]
- Change from baseline in safety laboratory values, vital sign measurements, ECG results, and physical/neurological examination findings [Timeframe: Up to 18 months]
Secondary endpoints 4
- DNL593 serum PK parameters (when feasible): Cmax, tmax, Ctrough, AUClast, AUCt , t 1/2, Accumulation ratio [Timeframe: Up to 18 months]
- Concentration of DNL593 in cerebrospinal fluid (CSF) [Timeframe: Up to 18 months]
- DNL593 CSF:serum concentration ratio [Timeframe: Up to 18 months]
- Percentage change from baseline in plasma Nfl at Week 25
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD9649687 · Product
- Active substance
- DNL593
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS
- Authorisation status
- Not Authorised
- MA holder
- DENALI THERAPEUTICS INC.
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
DNL593 Placebo, Sterile lyophilisate in single-dose glass vials
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
- Orphan designation
- No
Auxiliary 3
-
R06A · Product
- Pharmaceutical form
- -
- Route of administration
- ORAL AND IV
- Authorisation status
- Authorised
- ATC code
- R06A — ANTIHISTAMINES FOR SYSTEMIC USE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
-
H02AB · Product
- Pharmaceutical form
- PHF00170MIG
- Route of administration
- ORAL AND IV
- Authorisation status
- Authorised
- ATC code
- H02AB — GLUCOCORTICOIDS
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP127871 · ATC
- Active substance
- Famotidine
- Route of administration
- ORAL AND IV
- Authorisation status
- Authorised
- ATC code
- A02BA03 — FAMOTIDINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Denali Therapeutics Inc.
- Sponsor organisation
- Denali Therapeutics Inc.
- Address
- 161 Oyster Point Boulevard
- City
- South San Francisco
- Postcode
- 94080-2042
- Country
- United States
Scientific contact point
- Organisation
- Denali Therapeutics Inc.
- Contact name
- Amy Berger
Public contact point
- Organisation
- Denali Therapeutics Inc.
- Contact name
- Clinical Trials Group
Third parties 14
| Organisation | City, country | Duties |
|---|---|---|
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | Laboratory analysis |
| Fisher Clinical Services GmbH ORG-100017323
|
Weil Am Rhein, Germany | Code 14 |
| PPD Development L.P. ORG-100011560
|
Wilmington, United States | Code 12, Code 2, Code 5, Code 8, Code 9 |
| Scout Clinical ORG-100042228
|
Dallas, United States | Other |
| Primevigilance Limited ORG-100027742
|
Guildford, United Kingdom | Code 8 |
| Aperio Clinical Outcomes LLC ORG-100046387
|
Durham, United States | Data management |
| Thermo Fisher Scientific Inc. ORG-100045666
|
Waltham, United States | Other |
| Preventiongenetics LLC ORG-100043377
|
Marshfield, United States | Other |
| IQVIA Limited ORG-100008655
|
Reading, United Kingdom | Interactive response technologies (IRT) |
| Eresearchtechnology Inc. ORG-100013039
|
Pittsburgh, United States | E-data capture |
| Bioagilytix Labs LLC ORG-100013030
|
Durham, United States | Other |
| Cogstate Limited ORG-100044403
|
Melbourne, Australia | Other |
| Kcas LLC ORG-100043073
|
Olathe, United States | Other |
| Redenlab Pty Limited ORG-100051311
|
Melbourne, Australia | Other |
Locations
7 EU/EEA countries · 18 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruitment ended | 5 | 2 |
| Czechia | Ended | 5 | 1 |
| France | Ongoing, recruitment ended | 8 | 4 |
| Italy | Ongoing, recruitment ended | 12 | 4 |
| Netherlands | Authorised, recruiting | 3 | 1 |
| Portugal | Ongoing, recruitment ended | 7 | 3 |
| Spain | Ongoing, recruitment ended | 15 | 3 |
| Rest of world
Brazil, Turkey, Colombia, United States
|
— | 14 | — |
Investigational sites
Antwerp University Hospital
Neurology, Drie Eikenstraat 655, 2650, Edegem
UZ Leuven
Neurology, Herestraat 49, 3000, Leuven
Centre Hospitalier Universitaire De Nantes
CentreMémoire Ressources et Recherche, Boulevard Du Professeur Jacques Monod, 44800, Saint Herblain
Assistance Publique Hopitaux De Paris
Institut de la mémoire et de la maladie d’Alzheimer, Num Voie 47 A 83, 47 Boulevard De L Hopital, Paris
Centre Hospitalier Universitaire De Toulouse
Department of Neurology, 1 Place Du Docteur Joseph Baylac, 31300, Toulouse
Centre Hospitalier Universitaire Rouen
Department of Neurology, 1 Rue De Germont, Bp 96031, Rouen Cedex
Istituto Auxologico Italiano IRCCS
U.O. Neurologia e Laboratorio di Neuroscienze, Piazzale Brescia 20, 20149, Milan
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Unità Operativa di Neurologia, Piazzale Spedali Civili 1, 25123, Brescia
Careggi University Hospital
Dipartimento Neuromuscoloscheletrico e degli organi di senso - (Padiglione 25 CTO-Neuromotorio), Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Pia Fondazione Di Culto E Religione Card G Panico
U.O.C. Malattie Neurodegenerative, Via Pio X 4, 73039, Tricase
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Neurology, Dr. Molewaterplein 40, 3015 GD, Rotterdam
CCAB Centro Clinico Academico Braga Associacao
Serviço de Neurologia, Lugar De Sete Fontes S Victor, 4710-243, Braga
CNS Saude Lda.
Unidade de Demências, Bairro De Santo Antonio 47, 2560-280, Torres Vedras
Hospital Pedro Hispano
Departamento de Neurologia, Rua Doutor Eduardo Torres 1, 4450-113, Matosinhos
University Hospital Virgen Del Rocio S.L.
Neurology Department, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Universitario Donostia
Neurology Department, Pasealeku Doct. Begiristain 109, 20014, Donostia
Hospital Clinic De Barcelona
Neurology Department, Calle Villarroel 170, 08036, Barcelona
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 |
|---|---|---|---|---|---|
| Belgium | 2023-05-16 | 2023-10-23 | 2026-01-07 | ||
| France | 2023-04-12 | 2023-04-14 | 2026-01-07 | ||
| Italy | 2023-03-28 | 2023-04-13 | 2026-01-07 | ||
| Netherlands | 2023-02-28 | ||||
| Portugal | 2023-03-14 | 2023-06-02 | 2026-01-07 | ||
| Spain | 2022-09-22 | 2022-10-11 | 2026-01-07 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 6 · Art. 38 CTR
Temporary halt TH-29646
- Halt date
- 2023-12-11
- Member states concerned
- Belgium
- Publication date
- 2024-06-14
- Reason
- Sponsor decision, Safety related (clinical or pre-clinical results)
- Explanation
- This temporary halt was previously notified to all participating Member States under the Clinical Trial Directive, and now that the study has been transitioned to the Clinical Trial Regulation during the halt, it is being notified again as required in CTIS.] Per Protocol Section 4.1.5 (version 5), dosing for all participants would be halted if 2 participants experience severe (Grade 3 or higher) or serious AEs related to IRRs. On 30 August 2023, a Grade 3 IRR consistent with anaphylaxis was observed in a participant in this study. On 6 December 2023, a Grade 2 IRR consistent with anaphylaxis was observed in a 2nd participant. Both participants recovered on the day of the event. Additional details in the form of CIOMS report have been shared with all investigators, per our serious AE case processing procedures. Given that cohort stopping criteria were met per protocol, the Dose Escalation Committee for Part B (DEC-B, consisting of: Dr. Harro Seelaar of Erasmus Medical Center, the Netherlands; Dr. Leonel Takada, University of Sãu Paolo, Brazil; and the Sponsor Medical Monitor) met on 11 December 2023 and agreed to pause dosing, screening, and enrollment for all participants, effective immediately.
- Follow-up measures
- As mentioned above, both participants who experienced IRRs recovered on the day of the event. Both were discontinued from study intervention per protocol-specified individual dose-stopping criteria.
Following analysis of the study data to-date, the protocol will be updated with the addition of safety measures to reduce the risk of IRRs prior to further dosing. Resumption of dosing in this study will require agreement of the DEC-B and appropriate regulatory and ethics approvals. - Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-29648
- Halt date
- 2023-12-11
- Member states concerned
- Spain
- Publication date
- 2024-06-14
- Reason
- Sponsor decision, Safety related (clinical or pre-clinical results)
- Explanation
- This temporary halt was previously notified to all participating Member States under the Clinical Trial Directive, and now that the study has been transitioned to the Clinical Trial Regulation during the halt, it is being notified again as required in CTIS.] Per Protocol Section 4.1.5 (version 5), dosing for all participants would be halted if 2 participants experience severe (Grade 3 or higher) or serious AEs related to IRRs. On 30 August 2023, a Grade 3 IRR consistent with anaphylaxis was observed in a participant in this study. On 6 December 2023, a Grade 2 IRR consistent with anaphylaxis was observed in a 2nd participant. Both participants recovered on the day of the event. Additional details in the form of CIOMS report have been shared with all investigators, per our serious AE case processing procedures. Given that cohort stopping criteria were met per protocol, the Dose Escalation Committee for Part B (DEC-B, consisting of: Dr. Harro Seelaar of Erasmus Medical Center, the Netherlands; Dr. Leonel Takada, University of Sãu Paolo, Brazil; and the Sponsor Medical Monitor) met on 11 December 2023 and agreed to pause dosing, screening, and enrollment for all participants, effective immediately.
- Follow-up measures
- As mentioned above, both participants who experienced IRRs recovered on the day of the event. Both were discontinued from study intervention per protocol-specified individual dose-stopping criteria.
Following analysis of the study data to-date, the protocol will be updated with the addition of safety measures to reduce the risk of IRRs prior to further dosing. Resumption of dosing in this study will require agreement of the DEC-B and appropriate regulatory and ethics approvals. - Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-29650
- Halt date
- 2023-12-11
- Member states concerned
- France
- Publication date
- 2024-06-14
- Reason
- Sponsor decision, Safety related (clinical or pre-clinical results)
- Explanation
- This temporary halt was previously notified to all participating Member States under the Clinical Trial Directive, and now that the study has been transitioned to the Clinical Trial Regulation during the halt, it is being notified again as required in CTIS.] Per Protocol Section 4.1.5 (version 5), dosing for all participants would be halted if 2 participants experience severe (Grade 3 or higher) or serious AEs related to IRRs. On 30 August 2023, a Grade 3 IRR consistent with anaphylaxis was observed in a participant in this study. On 6 December 2023, a Grade 2 IRR consistent with anaphylaxis was observed in a 2nd participant. Both participants recovered on the day of the event. Additional details in the form of CIOMS report have been shared with all investigators, per our serious AE case processing procedures. Given that cohort stopping criteria were met per protocol, the Dose Escalation Committee for Part B (DEC-B, consisting of: Dr. Harro Seelaar of Erasmus Medical Center, the Netherlands; Dr. Leonel Takada, University of Sãu Paolo, Brazil; and the Sponsor Medical Monitor) met on 11 December 2023 and agreed to pause dosing, screening, and enrollment for all participants, effective immediately.
- Follow-up measures
- As mentioned above, both participants who experienced IRRs recovered on the day of the event. Both were discontinued from study intervention per protocol-specified individual dose-stopping criteria.
Following analysis of the study data to-date, the protocol will be updated with the addition of safety measures to reduce the risk of IRRs prior to further dosing. Resumption of dosing in this study will require agreement of the DEC-B and appropriate regulatory and ethics approvals. - Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-29652
- Halt date
- 2023-12-11
- Member states concerned
- Portugal
- Publication date
- 2024-06-14
- Reason
- Sponsor decision, Safety related (clinical or pre-clinical results)
- Explanation
- This temporary halt was previously notified to all participating Member States under the Clinical Trial Directive, and now that the study has been transitioned to the Clinical Trial Regulation during the halt, it is being notified again as required in CTIS.] Per Protocol Section 4.1.5 (version 5), dosing for all participants would be halted if 2 participants experience severe (Grade 3 or higher) or serious AEs related to IRRs. On 30 August 2023, a Grade 3 IRR consistent with anaphylaxis was observed in a participant in this study. On 6 December 2023, a Grade 2 IRR consistent with anaphylaxis was observed in a 2nd participant. Both participants recovered on the day of the event. Additional details in the form of CIOMS report have been shared with all investigators, per our serious AE case processing procedures. Given that cohort stopping criteria were met per protocol, the Dose Escalation Committee for Part B (DEC-B, consisting of: Dr. Harro Seelaar of Erasmus Medical Center, the Netherlands; Dr. Leonel Takada, University of Sãu Paolo, Brazil; and the Sponsor Medical Monitor) met on 11 December 2023 and agreed to pause dosing, screening, and enrollment for all participants, effective immediately.
- Follow-up measures
- As mentioned above, both participants who experienced IRRs recovered on the day of the event. Both were discontinued from study intervention per protocol-specified individual dose-stopping criteria.
Following analysis of the study data to-date, the protocol will be updated with the addition of safety measures to reduce the risk of IRRs prior to further dosing. Resumption of dosing in this study will require agreement of the DEC-B and appropriate regulatory and ethics approvals. - Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-29643
- Halt date
- 2023-12-11
- Member states concerned
- Italy
- Publication date
- 2024-06-14
- Reason
- Sponsor decision, Safety related (clinical or pre-clinical results)
- Explanation
- This temporary halt was previously notified to all participating Member States under the Clinical Trial Directive, and now that the study has been transitioned to the Clinical Trial Regulation during the halt, it is being notified again as required in CTIS.] Per Protocol Section 4.1.5 (version 5), dosing for all participants would be halted if 2 participants experience severe (Grade 3 or higher) or serious AEs related to IRRs. On 30 August 2023, a Grade 3 IRR consistent with anaphylaxis was observed in a participant in this study. On 6 December 2023, a Grade 2 IRR consistent with anaphylaxis was observed in a 2nd participant. Both participants recovered on the day of the event. Additional details in the form of CIOMS report have been shared with all investigators, per our serious AE case processing procedures. Given that cohort stopping criteria were met per protocol, the Dose Escalation Committee for Part B (DEC-B, consisting of: Dr. Harro Seelaar of Erasmus Medical Center, the Netherlands; Dr. Leonel Takada, University of Sãu Paolo, Brazil; and the Sponsor Medical Monitor) met on 11 December 2023 and agreed to pause dosing, screening, and enrollment for all participants, effective immediately.
- Follow-up measures
- As mentioned above, both participants who experienced IRRs recovered on the day of the event. Both were discontinued from study intervention per protocol-specified individual dose-stopping criteria.
Following analysis of the study data to-date, the protocol will be updated with the addition of safety measures to reduce the risk of IRRs prior to further dosing. Resumption of dosing in this study will require agreement of the DEC-B and appropriate regulatory and ethics approvals. - Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Temporary halt TH-29645
- Halt date
- 2023-12-11
- Member states concerned
- Netherlands
- Publication date
- 2024-06-14
- Reason
- Sponsor decision, Safety related (clinical or pre-clinical results)
- Explanation
- This temporary halt was previously notified to all participating Member States under the Clinical Trial Directive, and now that the study has been transitioned to the Clinical Trial Regulation during the halt, it is being notified again as required in CTIS.] Per Protocol Section 4.1.5 (version 5), dosing for all participants would be halted if 2 participants experience severe (Grade 3 or higher) or serious AEs related to IRRs. On 30 August 2023, a Grade 3 IRR consistent with anaphylaxis was observed in a participant in this study. On 6 December 2023, a Grade 2 IRR consistent with anaphylaxis was observed in a 2nd participant. Both participants recovered on the day of the event. Additional details in the form of CIOMS report have been shared with all investigators, per our serious AE case processing procedures. Given that cohort stopping criteria were met per protocol, the Dose Escalation Committee for Part B (DEC-B, consisting of: Dr. Harro Seelaar of Erasmus Medical Center, the Netherlands; Dr. Leonel Takada, University of Sãu Paolo, Brazil; and the Sponsor Medical Monitor) met on 11 December 2023 and agreed to pause dosing, screening, and enrollment for all participants, effective immediately.
- Follow-up measures
- As mentioned above, both participants who experienced IRRs recovered on the day of the event. Both were discontinued from study intervention per protocol-specified individual dose-stopping criteria.
Following analysis of the study data to-date, the protocol will be updated with the addition of safety measures to reduce the risk of IRRs prior to further dosing. Resumption of dosing in this study will require agreement of the DEC-B and appropriate regulatory and ethics approvals. - Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 102 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Denali_DNLI-H-0001_FR_ANSM_Approval_FR_ENG_Public | 5 |
| Protocol (for publication) | D1_Denali_DNLI-H-0001_FR_EC_Fav opinion_FR_ENG_Public | 5 |
| Protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_CZE_Public | 8.0 |
| Protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol_2023-508697-28_Public | 8.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_BE_ENG_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_BE_FRA_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_BE_NDL_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_CZ_CZE_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_CZ_ENG_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_ES_SPA_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_FR_FRA_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_IT_ITA_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_NL_NDL_Public | 1.0 |
| Protocol (for publication) | D4_Denali_DNLI-H-0001_All patient-facing materials_PT_POR_Public | 1.0 |
| Recruitment arrangements (for publication) | K1_DNLI-H-0001_Recruitment_and_Informed_consent_procedure_CZ_English | 1.0 |
| Recruitment arrangements (for publication) | K1_DNLI-H-0001_Recruitment-and-Informed-Consent-Procedure_PT_Public | 1 |
| Recruitment arrangements (for publication) | K1_DNLI-H-0001_Recruitment-Arrangements_BE_English_Public | 1.0 |
| Recruitment arrangements (for publication) | K1_DNLI-H-0001_Recruitment-Arrangements_ES_Public | 1 |
| Recruitment arrangements (for publication) | K1_DNLI-H-0001_Recruitment-Arrangements_FR_French_Public | 1 |
| Recruitment arrangements (for publication) | K1_DNLI-H-0001_Recruitment-Arrangements_IT_Public | 1.0 |
| Recruitment arrangements (for publication) | K1_DNLI-H-0001_Recruitment-arrangements_NL_English_Public | n/a |
| Recruitment arrangements (for publication) | K1_DNLI-H-0001_Referral-Letter_PT_Portuguese_clean_Public | 3.0 |
| Recruitment arrangements (for publication) | K2_DNLI-H-0001_GP letter_IT_Italian_Public | 2.0 |
| Recruitment arrangements (for publication) | K2_DNLI-H-0001_Referral-Letter_ES_Spanish_clean_Public | 3.0 |
| Recruitment arrangements (for publication) | K2_DNLI-H-0001_Referral-letter_IT_Italian_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Main-ICF-B_BE_Dutch_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Main-ICF-B_BE_English_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Main-ICF-B_BE_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Main-ICF-C_BE_Dutch_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Main-ICF-C_BE_English_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Main-ICF-C_BE_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Study-Partner-caregiver-ICF_BE_Dutch_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Study-Partner-caregiver-ICF_BE_English_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNL-H-0001_Study-Partner-caregiver-ICF_BE_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001 Main-ICF-Part B_ES_Spanish_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Caregiver ICF_FR_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Caregiver_ICF_IT_Italian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Future-Use-ICF_BE_Dutch_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Future-Use-ICF_BE_English_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Future-Use-ICF_BE_French_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Future-Use-ICF_FR_French_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_GDPR ICF_CZ_Czech_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_GUID ICF_CZ_Czech_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_GUID ICF_ES_Spanish_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_GUID-ICF_PT_Portuguese_clean_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Main ICF Part B_CZ_Czech_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Main ICF Part C_CZ_Czech_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Main part B ICF_FR_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Main part C ICF_FR_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Main-ICF-Part-C_ES_Spanish_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Main-Part B-ICF_PT_Portuguese_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Main-Part C-ICF_PT_Portuguese_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_MainB_ICF_IT_Italian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_MainC_ICF_IT_Italian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Optional Future Research ICF_CZ_Czech_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Optional-Genetic-Testing-ICF_PT_Portuguese_clean_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_PP ICF_FR_French_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pre-ICF_Travel Reimbursement-Telephone-Data-Consent_ES_Spanish_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pre-Screening Genetic Test ICF_CZ_Czech_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pre-Screening-Genetic-Test_ES_Spanish_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pre-Screening-Genetic-Test-ICF_BE_Dutch_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pre-Screening-Genetic-Test-ICF_BE_English_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pre-Screening-Genetic-Test-ICF_BE_French_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pre-Screening-Genetic-Testing-ICF_PT_Portuguese_Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pregnancy and Newborn ICF_CZ_Czech_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pregnancy and Newborn ICF_IT_ITalian_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pregnancy-and-Newborn-ICF_ ES_Spanish_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pregnancy-and-Newborn-ICF_BE_Dutch_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pregnancy-and-Newborn-ICF_BE_English_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pregnancy-and-Newborn-ICF_BE_French_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Pregnancy-and-Newborn-ICF_PT_Portuguese_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_PreScreening ICF_FR_French_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_PreScreening_ICF_IT_Italian_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_SC_Pre-ICF Telephone-Data-Consent_PT_Portuguese_Public | 1.1 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Scout-ICF_ES_Spanish_clean_Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_SIS-and-ICF-Main-Part-B_NL_Dutch_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_SIS-and-ICF-Main-Part-C_NL_Dutch_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_SIS-and-ICF-Study-Partner_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Study Partner ICF_CZ_Czech_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Study-Partner-ICF_ES_Spanish_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Study-Partner-ICF_PT_Portuguese_Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Travel-Reimbursement-ICF_BE_Dutch_Public | 1.4 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Travel-Reimbursement-ICF_BE_English_Public | 1.4 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001_Travel-Reimbursement-ICF_BE_French_Public | 1.4 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-0001-Future-Use-ICF_PT_Portuguese_clean_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-001_Future Use ICF_IT_Italian_Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_DNLI-H-001_GUID ICF_IT_Italian_Public | 1.0 |
| Subject information and informed consent form (for publication) | L2_DNLI-H-0001_Country-Patient-Card_PT_Portuguese_Public | 2.0.0 |
| Subject information and informed consent form (for publication) | L2_DNLI-H-0001_S495-SC-PFD-Email Communication_PT_Portuguese_clean_Public | 2.0 |
| Subject information and informed consent form (for publication) | L2_DNLI-H-0001_S495-SC-PFD-ScoutPass-Reloadable-EUR_PT_Portuguese_Public | 1.1 |
| Subject information and informed consent form (for publication) | L2_DNLI-H-0001_S495-SC-PFD-Study Brochure_PT_Portuguese_Public | 1.0 |
| Subject information and informed consent form (for publication) | L2_DNLI-H-0001_ScoutPass-EUR_PT_Portuguese_Public | N/A |
| Subject information and informed consent form (for publication) | L2_DNLI-H-0001_Study-Partner-Autorization-Form_NL_Dutch_Public | 1.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_BE_DEU_Public | 8.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_BE_FRA_Public | 8.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_BE_NDL_Public | 8.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_ENG_Public | 8.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_ES_SPA_Public | 8.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_FR_FRA_Public | 8.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_IT_ITA_Public | 8.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_NL_NDL_Public | 8.0 |
| Synopsis of the protocol (for publication) | D1_Denali_DNLI-H-0001_Protocol Summary_2023-508697-28_PT_POR_Public | 8.0 |
Application history
10 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-08 | Netherlands | Acceptable 2024-05-15
|
2024-05-15 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-07 | Netherlands | Acceptable 2024-11-08
|
2024-11-08 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-12-30 | Acceptable | 2025-02-19 | |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-06-09 | Acceptable | 2025-07-18 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-06-13 | Acceptable | 2025-07-23 | |
| 6 | SUBSEQUENT ADDITION OF MSC | APP-6 | 2025-07-04 | 2025-09-05 | ||
| 7 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-09-19 | 2025-09-19 | ||
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-12-03 | Netherlands | 2025-12-03 | |
| 9 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-12-19 | Netherlands | Acceptable 2026-02-24
|
2026-02-24 |
| 10 | SUBSTANTIAL MODIFICATION | SM-6 | 2026-05-26 | Netherlands | Acceptable | 2026-05-29 |