MODAFIMS: An open-label, single-center clinical trial to evaluate predictors of response to MODAFinil in the treatment of cognitive deficits in patients with Multiple Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CCAB Centro Clinico Academico Braga Associacao

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Aug 2024 → ongoing

Decision date (initial)

2024-06-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Stichting Paeonia Foundation · CCAB Centro Clinico Academico Braga Associacao

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

- Identification of acute resting-state fMRI features that differentiate between responders and non-responders to modafinil at baseline.
- Identification of long-term resting-sate fMRI features that differentiate between responders and non-responders to modafinil after 3 months of treatment with modafinil.

Secondary objectives 8

1. Identification of acute fMRI features during task that differentiate between responders and non-responders to modafinil at baseline.
2. Identification of long-term fMRI features during task that differentiate between responders and non-responders to modafinil after 3 months of treatment with modafinil.
3. Assess the changes in the Perceived Deficits Questionnaire (PDQ), as compared to the baseline.
4. Assess the changes in processing speed as compared to the baseline.
5. Assess the changes in executive function as compared to the baseline.
6. Assess the changes in QoL as compared to the baseline.
7. Assess the changes in working ability as compared to the baseline.
8. Assess the changes in fatigue as compared to the baseline.

Conditions and MedDRA coding

Multiple sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Participant is willing and able to give informed consent for the participation in the trial
2. Patients that are able to read and write
3. Male or female, aged between 18 and 64 years old at the time of signing the ICF
4. Diagnosed with Relapsing-Remitting MS or Clinically Isolated Syndrome, according to McDonald 2017 diagnostic criteria (Thompson et al., 2018).
5. Expanded disability status score (EDSS) less than 6.5.
6. Presence of subjective cognitive complaints
7. SDMT score (number of correct responses within 90 seconds) at Screening ≤ 55 (Benedict et al., 2016; Parmenter et al., 2007).
8. Female participants of childbearing potential and male participants whose partner is of childbearing potential must be willing to ensure that they or their partner use protocol’s recommended effective contraception methods, which is not based only on hormonal methods, during all the 6 months of the trial (3 months of treatment plus 3 months of safety follow-up).
9. Male participants must agree to refrain from donation of semen from first study treatment administration up to at least 90 days after last administration.
10. Participants, that in the medical investigator’s opinion, are able and willing to comply with all trial requirements.

Exclusion criteria 26

1. Female participant who is pregnant, breastfeeding or planning pregnancy during the trial.
2. Significant neurological history aside from MS (e.g., Epilepsy).
3. Significant psychiatric history (e.g., Schizophrenia, Bipolar Disorder, Major Depression, severe anxiety disorder, aggressive or hostile behaviour).
4. A documented history of attempted suicide in the last 2 years OR suicidal ideation with intent, with or without a plan or method (e.g., positive response to items 4 or 5 in the assessment of suicidal ideation on the C-SSRS) over the 6 months prior to the Screening Visit.
5. Significant insomnia (grade > 1 according to Common Terminology Criteria for Adverse Events, CTCAE v5).
6. History of severe hypersensitivity reactions to any medicine
7. Presence of any clinically significant abnormality in ECG morphology or ECG parameters
8. Known immunodeficiency syndrome
9. Have serum alanine aminotransferase (ALT) values greater than 3 times the upper limit of normal at screening
10. Positive test for anti-Human Immunodeficiency virus 1 or 2 antibodies, Hepatitis B surface antigen (HBsAg) or anti Hepatitis C virus antibodies.
11. Creatinine clearance < 20 ml/min determined by Cockcroft-Gault equation.
12. Participants who have participated in another research trial involving an investigational product within the past 5 half-lives of the other investigational product
13. History of alcoholism or drug abuse.
14. Average daily consumption of more than 20 cigarettes.
15. Participants with disability that interferes with the performance of the CT procedures (for example, motor deficit in upper limb, decreased visual acuity even with correction).
16. Participants with increased risk of epileptic seizures, history of cardiac arrhythmias, or uncontrolled moderate to severe hypertension.
17. Participants taking warfarin or any other prohibited medication.
18. Any other condition that, in the opinion of the investigator, contra-indicates the participation of the patient.
19. Participants who have any disability that, in the opinion of the investigator, significantly interferes with the neuropsychological testing and/or the tasks in the functional MRI
20. Participants not able to undergo MRI scanning
21. Participants who have any contra-indication for taking modafinil, according to the prescribing information and SmPC, such as hypersensitivity to the active substance and any excipient present in the modafinil or any documented adverse reaction after modafinil intake
22. Participants with known hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption
23. Participants with a history of left ventricular hypertrophy or cor pulmonale and patients with mitral valve prolapse who developed mitral valve prolapse syndrome when previously treated with central nervous system stimulants
24. Current use of modafinil, armodafinil
25. Current use of other psychostimulants, including amphetamines, cocaine, bupropion, gingko biloba, among others, and beverages or food containing methylxanthines (e.g., coffee, tea, cola, caffeine, chocolate, sodas) exceeding 500 mg methylxanthines per day (for example, consumption of more than 5 espresso coffees or 100 mg of dark chocolate per day; Sanchez, 2017).
26. Sleep complaints confirmed by Epworth Sleepiness Scale (ESS) scale score >10 at screening visit OR known sleep disorder.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes in brain function and connectivity measured using resting state fMRI (at baseline and after 3 months of treatment with Modafinil). Functional MRI will be performed at baseline, before and 3h (±30 min) after Modafinil administration, and at the end of treatment (3-month visit).

Secondary endpoints 2

1. Changes in brain function and connectivity measured using a Go/no-Go task fMRI.
2. Changes in patient reported outcomes (PROs) and neuropsychological tests - Perceived Deficits Questionnaire (PDQ), Symbol Digit Modalities Test (SDMT), Stroop test measured as interference index, MS-specific QoL questionnaire, Work Productivity and Activity Impairment Questionnaire for MS (WPAI:MS) and Modified Fatigue Impact Scale (MFIS). These assessments will occur in the screening or baseline visits and at the end of treatment (3-month visit).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CCAB Centro Clinico Academico Braga Associacao

Sponsor organisation

CCAB Centro Clinico Academico Braga Associacao

Address

Lugar De Sete Fontes S Victor

City

Braga

Postcode

4710-243

Country

Portugal

Scientific contact point

Organisation

CCAB Centro Clinico Academico Braga Associacao

Contact name

Clinical Project Manager

Public contact point

Organisation

CCAB Centro Clinico Academico Braga Associacao

Contact name

Executive director

Locations

1 EU/EEA country · 1 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 10 files

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

Application history

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