TestOsterone TreatmEnt on neuroprotection and Myelin repair in Relapsing Remitting Multiple Sclerosis (TOTEM-RRMS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Patients

Age range

18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

3 Oct 2024 → ongoing

Decision date (initial)

2024-10-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

BAYER PHARMA · DGOS · GRUNENTHAL · FHU Neurogenycs

External identifiers

EU CT number

2024-517845-14-00

EudraCT number

2018-002648-10

ClinicalTrials.gov

NCT03910738

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate the remyelinating and neuroprotective effect of testosterone
treatment used for 54 weeks in patients with RRMS treated with
natalizumab , fingolimod, ponesimod, ocrelizumab or ofatumumab on a
criterion combining the analysis of thalamus atrophy and diffusion
tensor measured by MRI.

Secondary objectives 3

1. - To Evaluate the effectiveness of the treatment on advanced parameters in MRI.
2. To evaluate the clinical effectiveness of the treatment and its tolerance.
3. Identify new biomarkers predictive of the evolution of the disease through the establishment of a biobank of blood samples

Conditions and MedDRA coding

Relapsing Remitting Multiple sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Man between 18 and 55 years
2. Confirmed and documented diagnosis of MS, as defined by the revised McDonald criteria
3. Patients who have been receiving one of the following diseasemodifying therapies for at least one year prior to randomization: natalizumab , fingolimod, ponesimod, ocrelizumab, or ofatumumab, in accordance with their prescribing information. . Switching from one molecule to another during the previous year is also permitted, provided that the switch was motivated by a non-neurological reason (relapse, MRI activity).Patients receiving ocrelizumab within 6 to 9 months are eligible, provided they have received full-dose ocrelizumab for at least 2 years".
4. Biological hypogonadism defined by serum total testosterone levels below 20 nmol / L (checked by blood sampling during the screening visit)
5. For patients under natalizumab :Negative status for JC virus or JC virus synthesis index ≤ 1.5 (within 6 months prior to screening visit)
6. No relapses in the year prior to inclusion
7. Stable neurological state in the month preceding randomization

Exclusion criteria 12

1. Patients with progressive MS (primary or secondary)
2. Patients with hypogonadism with clinical symptoms and treated with androgens
3. Patients with PSA (prostate specific antigen)> 2.5 ng / ml (for an age less than 49 years old) or> 3.5 ng / ml (for age ≥ 50 years) (checked by a blood test at screening visit)
4. Patients with a hematocrit level > 54% (checked by blood sampling during the screening visit)
5. Patients with any other disease other than MS that may contribute to neurological symptoms and signs or affect their evaluation
6. Patients with neurological signs compatible with PML or confirmed PML
7. Patients diagnosed with untreated sleep apnea
8. Patients with or having had cancer or tumors of the liver, heart, kidney, XML File Identifier: 0bHUQtIJ9JZx4QdRJTxm0++LBOc= Page 12/24 prostate or mammary gland
9. Patients with cardiovascular, renal, hepatic, hematological, gastrointestinal, pulmonary, uncontrolled diseases
10. Patients with chronic infectious disease
11. Patients with a history of hypersensitivity to Nebido® or any of the excipients, or drugs of similar chemical classes
12. Patients who used experimental drugs and / or who participated in clinical drug trials in the 6 months prior to selection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Binary criterion comparing the success rate in each treatment group, defined by thalamic atrophy less than 0.5% per year and / or a decrease in transverse diffusivity in lesions less than 0.5% per year.

Secondary endpoints 5

1. Efficiency of treatment by imaging: XML File Identifier: 0bHUQtIJ9JZx4QdRJTxm0++LBOc= Page 13/24 • evolution of conventional MRI parameters: volume and number of T1 hypointense lesions, volume and number of new or enlarged T2 lesions, total volume of hyper-intensity FLAIR. • evolution of unconventional MRI parameters: diffusion tensor imaging (NODDI), quantitative magnetization transfer imaging (MPF).
2. Clinical efficiency of treatment: • Brief International Cognitive Assessment for Multiple Sclerosis, test consisting of the symbol digit modalities test, the California Verbal Learning Test Second Edition, and the Brief Visuospatial Memory Test Revised test • Changes in quality of life and health-related quality of life as measured by the SF-36 and EQ-5D questionnaires respectively.
3. Clinical efficiency of treatment:Impact of MS on workplace productivity and day-to-day activities, as assessed by the WPAI (Work productivity and activity impairment) questionnaire. • Impact on fatigue, as measured by the Multi-Dimensional Fatigue Impact Scale (MFIS),
4. Clinical efficiency of treatment:Hospital assessment scale for anxiety and depression, as measured by the hospital anxiety and depression scale (HADS) questionnaire. • Evolution of handicap by the EDSS Score
5. Safe use of the treatment: number and nature of adverse events, evaluation of vital signs at each visit, clinical and neurological examinations, biological results, locally interpreted MRI for tolerance (non-MS pathology of the CNS) and monitoring of concomitant medications ( outside Tysabri®).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Place De L Hopital, Cs 80426 Cs 80426

City

Strasbourg Cedex

Postcode

67091

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Nicolas COLLONGUES

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Nicolas COLLONGUES

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 9 files

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

Application history

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