Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
50
Countries
1
Sites
7
Multiple sclerosis
The objective of the study is to determine the safety of TAF as an add-on therapy to natalizumab.
Key facts
- Sponsor
- Helse Bergen HF
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 6 Feb 2024 → 14 Nov 2025
- Decision date (initial)
- 2023-11-20
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Gilead Sciences · The norwegian MS patient organization "MS Forbundet" · Helse Vest
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety
The objective of the study is to determine the safety of TAF as an add-on therapy to natalizumab.
Secondary objectives 1
- Determine the effect of TAF on Epstein-Barr virus activity in patients with RRMS
Conditions and MedDRA coding
Multiple sclerosis
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | 6 month treatment phase There are two treatment arms in the study - test and comparator.
|
Randomised Controlled | Double | [{"id":87683,"code":5,"name":"Carer"},{"id":87684,"code":4,"name":"Analyst"},{"id":87686,"code":2,"name":"Investigator"},{"id":87685,"code":1,"name":"Subject"},{"id":87687,"code":3,"name":"Monitor"}] | TAF 25 mg: Test Placebo: Comparator |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- 1. Age ≥ 18 to ≤ 70 years, both male and female patients
- 2. Diagnosis of RRMS using revised McDonald criteria of clinically definite MS.1
- 3. Currently treated with natalizumab
- 4. Demonstrated shedding of EBV in salvia (Shedding is defined as at least one salvia sample with >5.8 virus copies/µL cut-off)
Exclusion criteria 16
- 1. Known hypersensitivity or other serious adverse reaction to the active agent or other component of the study medication.
- 10. ALAT more than 2 times the upper normal reference limit (ULN)
- 11. Serum creatinine > 200 µmol/L
- 12. Serum bilirubin > 2 times the ULN
- 13. Any other disease that can influence the patient safety and compliance, or the evaluation of outcome
- 14. Currently enrolled in other trials of an investigational drug, or less than 30 days since ending another investigational drug.
- 15. Contraindications to undergo MRI such as a history of claustrophobia, inability to lie flat for approximately one hour, or metal implants (metal pins or plates, extensive non-removable dental work, cerebral aneurysm clips, pacemaker) as assessed by a standardized screening form
- 2. Women who are pregnant, as verified by a serum pregnancy test at screening and during follow-up, or lactating
- 3. Any ongoing infection with HIV, chronic active hepatitis, hepatitis C, or hepatitis B surface antigen positivity
- 4. History of pancreatitis
- 5. Prior or current disorders influencing the patient’s ability to give an informed consent or to comply with treatment and follow-up of the protocol
- 6. Current users of medications that could interact with the study medication (listed in paragraph 5.6)
- 7. Patients who previously have been treated with hematopoietic stem cell transplantation (HSCT)
- 8. WBC < 1.5 x 109 /L if not caused by a reversible effect of documented ongoing medication. If WBC < 1.5 x 109 /L is caused by a reversible effect of documented ongoing medication the WBC count must be > 1,5 x 109 /L before start of study treatment.
- 9. Platelet (thrombocyte) count < 100 x 109 /L
- Creatinin clearance < 15 ml/min
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Total number of SAEs from baseline to 24 weeks after start of study treatment
Secondary endpoints 3
- Change in IgG antibodies to EBNA1 and other EBV antigens from baseline to 2, 8 and 24 weeks after start of study treatment.
- Change in EBV viral load in saliva from baseline to 2, 8 and 24 weeks after start of study treatment.
- Key secondary endpoints Change in EBV shedding in saliva
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Vemlidy 25 mg film-coated tablets.
PRD4659207 · Product
- Active substance
- Tenofovir Alafenamide
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 180 Day(s)
- Authorisation status
- Authorised
- ATC code
- J05AF13 — -
- Marketing authorisation
- EU/1/16/1154/001
- MA holder
- GILEAD SCIENCES IRELAND UC
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- Route of administration
- ORAL
- Max daily dose
- 0 mg milligram(s)
- Max total dose
- 0 mg milligram(s)
- Max treatment duration
- 6 Week(s)
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 1
Tysabri 300 mg concentrate for solution for infusion
PRD10194542 · Product
- Active substance
- Natalizumab
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INFUSION
- Max daily dose
- 300 mg milligram(s)
- Max total dose
- 1200 mg milligram(s)
- Max treatment duration
- 6 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AA23 — -
- Marketing authorisation
- EU/1/06/346/001
- MA holder
- BIOGEN NETHERLANDS B.V.
- MA country
- Iceland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Helse Bergen HF
- Sponsor organisation
- Helse Bergen HF
- Address
- Jonas Lies Vei 65
- City
- Bergen
- Postcode
- 5021
- Country
- Norway
Scientific contact point
- Organisation
- Helse Bergen HF
- Contact name
- Øivind Torkildsen
Public contact point
- Organisation
- Helse Bergen HF
- Contact name
- Øivind Torkildsen
Locations
1 EU/EEA country · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Norway | Ended | 50 | 7 |
| Rest of world | — | 0 | — |
Investigational sites
Helse Stavanger HF
Department of Neurology, Stavanger University Hospital, P. O. Box 8100, 4068, Stavanger
Helse Bergen HF
Department of Neurology Haukeland University Hospital, Jonas Lies Vei 65, 5021, Bergen
Oslo University Hospital HF
Department of Neurology, Oslo University Hospital, P. O. Box 4953, 0424, Oslo
Helse Fonna HF
Department of Neurology, P. O. Box 2170, 5504, Haugesund
Drammen Sykehus
Department of Neurology, Dronninggata 28, 3004, Drammen
Helse Forde HF
Department of Neurology, Svanehaugvegen 2, 6812, Foerde
Akershus University Hospital
Department of Neurology, Sykehusveien 27, 1478, Lorenskog
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 |
|---|---|---|---|---|---|
| Norway | 2024-02-06 | 2025-11-14 | 2024-02-06 | 2025-03-26 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 3 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_ Protocol EU CT 2023-503814-62-00 | 6.0 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC_Vemlidy | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_NO EU CT number 2023-503814-62-00 | 4.0 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-08-11 | Norway | Acceptable 2023-11-16
|
2023-11-20 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-03-26 | Norway | Acceptable 2024-05-10
|
2024-05-16 |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-10-09 | Norway | Acceptable 2024-11-08
|
2024-11-08 |