Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
250
Countries
6
Sites
16
Huntington's Disease
Safety - Evaluate the long-term safety of Votoplam in participants with Huntington’s disease (HD) Efficacy - Evaluate the pharmacodynamic effects of Votoplam through the reduction in blood total huntingtin (tHTT) levels
Key facts
- Sponsor
- Novartis Pharma AG
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 31 Oct 2023 → ongoing
- Decision date (initial)
- 2023-11-30
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Novartis Pharma AG
External identifiers
- EU CT number
- 2023-504628-24-00
- WHO UTN
- U1111-1291-8014
- ClinicalTrials.gov
- NCT06254482
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy, Dose response, Pharmacodynamic, Pharmacokinetic
Safety - Evaluate the long-term safety of Votoplam in participants with Huntington’s disease (HD)
Efficacy - Evaluate the pharmacodynamic effects of Votoplam through the reduction in blood total huntingtin (tHTT) levels
Secondary objectives 2
- Assess the long-term effects of Votoplam on change in caudate volume by volumetric magnetic resonance imaging (vMRI) Assess the long-term effect of PTC518 on change in composite Unified Huntington’s Disease Rating Scale (cUHDRS)
- Determine the long-term effect of Votoplam on mutant Huntingtin (mHTT) protein levels in cerebrospinal fluid (CSF) and blood
Conditions and MedDRA coding
Huntington's Disease
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10070668 | Huntington's disease | 100000004850 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Study design This is a double-blind, randomized, Phase 2b study to evaluate the long-term safety and efficacy of PTC518 in participants with HD. Participants who completed the Treatment Period in the Phase 2a Study PTC518-CNS-002-HD and fulfill the enrollment criteria and choose to enroll will all receive active PTC518.
Participants who received PTC518 in Study PTC518-CNS-002-HD will continue at the same dose level they received in that study in a blinded fashion (5, 10, or 20 mg). Participants who received placebo in Study PTC518-CNS-002-HD will be allocated to a PTC518 dose level according to the same dosing group in which they were previously randomized (5, 10, or 20 mg).
|
Randomised Controlled | Double | [{"id":183061,"code":1,"name":"Subject"},{"id":183064,"code":4,"name":"Analyst"},{"id":183062,"code":2,"name":"Investigator"},{"id":183063,"code":3,"name":"Monitor"}] |
Regulatory references
- Plan to share IPD
- No
| EU CT number | Title | Sponsor |
|---|---|---|
| 2020-003439-33 | Phase 1 Dose Escalation Study Assessing the Safety and Pharmacokinetics of PTC518 in Healthy Subjects. | |
| 2021-003852-18 | A PHASE 2A, RANDOMIZED, PLACEBO-CONTROLLED, DOSE-RANGING STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PTC518 IN SUBJECTS WITH HUNTINGTON'S DISEASE | |
| 2021-006463-23 | Phase 1 open-label, crossover study to evaluate the effect of food on the pharmacokinetics and safety of a single oral dose of PTC518 in healthy volunteers |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Ambulatory male or female participant aged 25 years and older, inclusive, who has completed the Treatment Period in Study PTC518-CNS-002-HD
- Participant is willing and able to provide informed consent and comply with all protocol requirements
- Women of childbearing potential (WOCBP) must agree to use highly effective methods of contraception during dosing and for 6 months after stopping the study medication.
- Sexually active and fertile males must use a condom during intercourse while taking study drug and for 6 months after stopping study drug and should neither father a child nor donate sperm in this period. A condom is required to be used also by vasectomized men in order to prevent potential delivery of the drug via seminal fluid.
Exclusion criteria 1
- Individuals are not eligible to participate in this study if they have not previously completed the Treatment Period in Study PTC518-CNS-002-HD.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Safety profile as characterized by TEAEs, laboratory abnormalities, vital signs, physical examination, C-SSRS
- Evaluate blood tHTT protein levels over time
Secondary endpoints 4
- Change in caudate volume as assessed by vMRI over time
- Change in cUHDRS scores over time
- Evaluate CSF mHTT protein levels over time
- Evaluate blood mHTT protein levels over time
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD12905244 · Product
- Active substance
- Votoplam
- Substance synonyms
- 2-(3-(2,2,6,6-tetramethylpiperidin-4-yl)-3H-[1,2,3]triazolo [4,5-c]pyridazin-6-yl)-5-(2H-1,2,3-triazol-2-yl)phenol, PTC518, PTC-0409973
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 48 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EMA/OD/0000184238
PRD12905245 · Product
- Active substance
- Votoplam
- Substance synonyms
- 2-(3-(2,2,6,6-tetramethylpiperidin-4-yl)-3H-[1,2,3]triazolo [4,5-c]pyridazin-6-yl)-5-(2H-1,2,3-triazol-2-yl)phenol, PTC518, PTC-0409973
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 48 Month(s)
- Authorisation status
- Not Authorised
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EMA/OD/0000184238
Placebo 2
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
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
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Novartis Pharma AG
- Sponsor organisation
- Novartis Pharma AG
- Address
- Lichtstrasse 35
- City
- Basel
- Postcode
- 4056
- Country
- Switzerland
Scientific contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Public contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Third parties 13
| Organisation | City, country | Duties |
|---|---|---|
| Suvoda LLC ORG-100043523
|
Conshohocken, United States | Interactive response technologies (IRT) |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | Other, E-data capture |
| Evotec International GmbH ORL-000001438
|
Germany | Laboratory analysis |
| Curia Bio, Inc ORL-000001439
|
United States | Laboratory analysis |
| Clario ORL-000001443
|
United States | Other, Other |
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 2, Ireland | Code 12, Code 8 |
| Aptuit (Verona) S.r.l. ORG-100014738
|
Verona, Italy | Laboratory analysis |
| Kcas LLC ORG-100043073
|
Olathe, United States | Laboratory analysis |
| Ixico Technologies Limited ORG-100042142
|
London, United Kingdom | Code 13 |
| PPD Labs ORL-000001440
|
Belgium | Laboratory analysis |
| MD Group ORL-000001445
|
United Kingdom | Other |
| Symbiance ORL-000001444
|
United States | Data management |
| Worldwide Clinical Trials ORG-100030991
|
Grad Zagreb, Croatia | On site monitoring, Code 12, Other, Code 5, Data management, Code 8 |
Locations
6 EU/EEA countries · 16 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Austria | Ongoing, recruitment ended | 12 | 1 |
| France | Ongoing, recruitment ended | 28 | 3 |
| Germany | Ongoing, recruitment ended | 36 | 4 |
| Italy | Ongoing, recruitment ended | 40 | 3 |
| Netherlands | Ongoing, recruitment ended | 24 | 1 |
| Spain | Ongoing, recruitment ended | 32 | 4 |
| Rest of world
New Zealand, United Kingdom, Australia, Canada
|
— | 78 | — |
Investigational sites
Medizinische Universitaet Innsbruck
Universitäts-Klinik für Neurologie, Anichstrasse 35, 6020, Innsbruck
Centre Hospitalier Universitaire D Angers
Neurology, 4 Rue Larrey, 49933, Angers Cedex 9
Assistance Publique Hopitaux De Paris
Neurology, 47 Boulevard De L Hopital, 75651, Paris Cedex 13
Assistance Publique Hopitaux De Marseille
Service de Neurologie et pathologie du mouvement, 264 Rue Saint Pierre, 13005, Marseille
Katholisches Klinikum Bochum gGmbH
Huntington-Center NRW, Gudrunstrasse 56, Grumme, Bochum
Charite Universitaetsmedizin Berlin KöR
Neurology, Chariteplatz 1, Mitte, Berlin
Universitaetsklinikum Ulm AöR
Klinik für Neurologie, Oberer Eselsberg 45, Eselsberg, Ulm
George-Huntington-Institut GmbH
R&D-Campus / Technologiepark Münster, Wilhelm-Schickard-Strasse 15, Sentrup, Muenster
IRCCS Foundation Istituto Neurologico Carlo Besta
Department of Diagnostics and Technologies, Via Giovanni Celoria 11, 20133, Milan
Casa Sollievo Della Sofferenza
Research and Treatment of Huntington and Rare Diseases, Viale Convento Cappuccini 1, 71013, San Giovanni Rotondo
Azienda Unita Sanitaria Locale Di Bologna
Neurology, Via Castiglione 29, 40124, Bologna
Leids Universitair Medisch Centrum (LUMC)
Neurology, Albinusdreef 2, 2333 ZA, Leiden
Hospital Universitario De Cruces
Neurology, Cruces Plaza S/n, 48903, Barakaldo
Hospital Universitario De Burgos
Neurology, Avenida De Las Islas Baleares 3, 09006, Burgos
Hospital De La Santa Creu I Sant Pau
Neurology, Carrer De San Quinti 89, 08041, Barcelona
Hospital Universitario Ramon Y Cajal
Neurology, Carretera Del Colmenar Viejo Km 9 100, Por El Pardo, Madrid
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 | 2024-07-29 | 2024-08-22 | 2025-01-27 | ||
| France | 2023-11-07 | 2023-12-08 | 2025-02-05 | ||
| Germany | 2023-10-31 | 2023-11-16 | 2025-01-29 | ||
| Italy | 2024-06-19 | 2024-07-30 | 2025-02-04 | ||
| Netherlands | 2023-11-29 | 2023-12-14 | 2025-01-16 | ||
| Spain | 2025-01-03 | 2025-01-03 | 2025-02-05 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 84 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol - Signature Page_2023-504628-24-00_1_English_Red | v25Mar2026 |
| Protocol (for publication) | D1_Protocol_2023-504628-24-00_1_English_Red | 08 |
| Protocol (for publication) | D4_C-SSRS_SLV_ESP_es | 1.0 |
| Protocol (for publication) | D4_C-SSRS_SLV_ITA_it | 1.0 |
| Protocol (for publication) | D4_C-SSRS_SLV_NLD_Dutch | 1.0 |
| Protocol (for publication) | D4_CCI_NLD_Dutch_redacted | 1.0 |
| Protocol (for publication) | D4_FuRST_ESP_es_redacted | 1.0 |
| Protocol (for publication) | D4_FuRST_ITA_it_redacted | 1.0 |
| Protocol (for publication) | D4_FuRST_NLD_Dutch_redacted | 1.0 |
| Protocol (for publication) | D4_Pacient_facing_CCI_FRA_French_redacted | 1.0 |
| Protocol (for publication) | D4_Pacient_facing_CCI_German_redacted | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_C-SSRS_SLV_DEU | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_C-SSRS_SLV_FRA | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_FuRST_DEU_Redacted | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_FuRST_FRA_Redacted | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_PBA-s_DEU_Redacted | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_PBA-s_FRA_Redacted | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_UHDRS_DEU_Redacted | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_UHDRS_FRA_Redacted | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_VFT_FRA | 1.0 |
| Protocol (for publication) | D4_Patient_facing_document_VTF_DEU | 1.0 |
| Protocol (for publication) | D4_PBA-s_ESP_es_redacted | 1.0 |
| Protocol (for publication) | D4_PBA-s_ITA_it_redacted | 1.0 |
| Protocol (for publication) | D4_PBA-s_NLD_Dutch_redacted | 1.0 |
| Protocol (for publication) | D4_Precision Motion Verbal Instructions to Participants_FRENCH_redacted | 1.0 |
| Protocol (for publication) | D4_Precision Motion Verbal Instructions to Participants_GERMAN_redacted | 1.0 |
| Protocol (for publication) | D4_Precision Motion Verbal Instructions to Participants_NLD_DUTCH_redacted | 1.0 |
| Protocol (for publication) | D4_Precision Motor Verbal instructions_ESP_es_redacted | 1.0 |
| Protocol (for publication) | D4_Precision Motor Verbal instructions_ITA_it_redacted | 1.0 |
| Protocol (for publication) | D4_SDMT_Alt Form 1_English_Redacted | 1.0 |
| Protocol (for publication) | D4_SDMT_Alt Form 2_English_Redacted | 1.0 |
| Protocol (for publication) | D4_SDMT_English_Redacted | 1.0 |
| Protocol (for publication) | D4_STROOP_ESP_es_redacted | 1.0 |
| Protocol (for publication) | D4_STROOP_French_Redacted | 1.0 |
| Protocol (for publication) | D4_STROOP_German_Redacted | 1.0 |
| Protocol (for publication) | D4_STROOP_ITA_it_redacted | 1.0 |
| Protocol (for publication) | D4_STROOP_NLD_Dutch_redacted | 1.0 |
| Protocol (for publication) | D4_TNSc_ESP_es_redacted | 1.0 |
| Protocol (for publication) | D4_TNSc_ITA_it_redacted | 1.0 |
| Protocol (for publication) | D4_UDHRS_ESP_es_redacted | 1.0 |
| Protocol (for publication) | D4_UDHRS_ITA_it_redacted | 1.0 |
| Protocol (for publication) | D4_UHDRS_NLD_Dutch_redacted | 1.0 |
| Protocol (for publication) | D4_VFT_ESP_es | 1.0 |
| Protocol (for publication) | D4_VFT_ITA_it | 1.0 |
| Protocol (for publication) | D4_VFT_NLD_Dutch | 1.0 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 3.1 |
| Recruitment arrangements (for publication) | K1_Additional document_Redacted | na |
| Recruitment arrangements (for publication) | K1_NLD_Recruitment arrangements | 3.1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements ES_public | 3.1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_FR_Public | 3.0 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_ITA_Public | 3.1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_Track Changes | 3.1 |
| Recruitment arrangements (for publication) | K1_Recruitment_arrangements_AUT | 3.1 |
| Subject information and informed consent form (for publication) | L1_ICFs_Main_Redacted | 08.07.1 |
| Subject information and informed consent form (for publication) | L1_ICFs_Pregnant_Partner_Redacted | 08.02.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF LAR_Redacted | (08.05).1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_ES_redacted | 08.05.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_Redacted | 08.05.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Personal Data and Privacy_Redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_ES | 08.02.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Pregnant Partner_ITA_Redacted | 08:02.1 |
| Subject information and informed consent form (for publication) | L1_SIS_and_ICF_Future_Research_redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS_and_ICF_Main_ICF_AUT_redacted | (08.05).1 |
| Subject information and informed consent form (for publication) | L1_SIS_and_ICF_Main_LAR_AUT_Redacted | 4.2 |
| Subject information and informed consent form (for publication) | L1_SIS_and_ICF_Main_redacted | (08.05).1 |
| Subject information and informed consent form (for publication) | L1_SIS_and_ICF_Pregnancy_Follow_Up_ICF_AUT_redacted | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS_and_ICF_Pregnant_Partner_DE_Public | (08:02).1 |
| Subject information and informed consent form (for publication) | L1_SIS_and_ICF_Pregnant_Partner_DE_Public | 1.2 |
| Subject information and informed consent form (for publication) | L1_SIS_and_ICF_Pregnant_Partner_ICF_AUT_redacted | (08:02).1 |
| Subject information and informed consent form (for publication) | L1_SIS_ICF_Main_redacted | (08.05).1 |
| Subject information and informed consent form (for publication) | L1_SIS_ICF_Pregnant_Partner_redacted | (08.02).1 |
| Subject information and informed consent form (for publication) | L2_Other-subject-information-material_MD-Group-welcome-letter_AUT_redacted | 1.0 |
| Subject information and informed consent form (for publication) | L2_site_details_for_ICF_AUT | 4.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Layperson Summary_Dutch_2023-504628-24-00_redacted | NA |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2023-504628-24-00_1_Dutch_Red | 05 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2023-504628-24-00_1_English_Red | 05 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2023-504628-24-00_1_French_Red | 05 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2023-504628-24-00_1_German_Red | 05 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2023-504628-24-00_1_Italian_Red | 05 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2023-504628-24-00_1_Spanish_Red | 05 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Technical Language_2023-504628-24-00_1_English_Red | 08 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Technical Language_2023-504628-24-00_1_French_Red | 08 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Technical Language_2023-504628-24-00_1_German_Red | 08 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Technical Language_2023-504628-24-00_1_Spanish_Red | 08 |
Application history
18 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-05-19 | Germany | Acceptable 2023-09-01
|
2023-09-04 |
| 2 | SUBSEQUENT ADDITION OF MSC | APP-2 | 2023-09-06 | Acceptable 2023-09-01
|
2023-11-30 | |
| 3 | SUBSEQUENT ADDITION OF MSC | APP-3 | 2023-09-06 | Acceptable 2023-09-01
|
2023-11-29 | |
| 4 | SUBSEQUENT ADDITION OF MSC | APP-4 | 2023-09-06 | 2023-12-04 | ||
| 5 | SUBSEQUENT ADDITION OF MSC | APP-5 | 2023-09-06 | Acceptable 2023-09-01
|
2023-11-13 | |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-01-11 | Germany | Acceptable 2023-09-01
|
2024-01-11 |
| 7 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-02-16 | Acceptable | 2024-04-01 | |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2024-05-21 | Germany | Acceptable | 2024-05-21 |
| 9 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2024-07-19 | Germany | Acceptable | 2024-07-19 |
| 10 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-07-25 | Germany | Acceptable | 2024-09-06 |
| 11 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-03-25 | Germany | Acceptable 2025-06-16
|
2025-06-17 |
| 12 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-07-09 | Germany | Acceptable 2025-09-24
|
2025-09-24 |
| 13 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-10-06 | Germany | Acceptable 2025-10-22
|
2025-10-22 |
| 14 | SUBSTANTIAL MODIFICATION | SM-7 | 2025-11-14 | Germany | Acceptable 2026-02-09
|
2026-02-10 |
| 15 | NON SUBSTANTIAL MODIFICATION | NSM-5 | 2026-02-26 | Germany | Acceptable 2026-02-09
|
2026-02-26 |
| 16 | NON SUBSTANTIAL MODIFICATION | NSM-6 | 2026-03-09 | Acceptable 2026-02-09
|
2026-03-09 | |
| 17 | NON SUBSTANTIAL MODIFICATION | NSM-7 | 2026-03-27 | Germany | Acceptable 2026-02-09
|
2026-03-27 |
| 18 | SUBSTANTIAL MODIFICATION | SM-9 | 2026-04-15 | Acceptable 2026-06-03
|
2026-06-03 |