Immune- and miRNA-response to Recombinant Interferon Beta in Healthy Volunteers and Patients With Relapsing Remitting Multiple Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 13 June 2016
• Main ID: NCT02364986
• Date of registration: 10/12/2014
• Prospective Registration: Yes
• Primary sponsor: PD Dr. Marcus Müller
• Public title: Immune- and miRNA-response to Recombinant Interferon Beta in Healthy Volunteers and Patients With Relapsing Remitting Multiple Sclerosis RESI
• Scientific title: Immune- and miRNA-response to Recombinant Interferon Beta in Healthy Volunteers and Patients With Relapsing Remitting Multiple Sclerosis
• Date of first enrolment: January 2015
• Target sample size: 50
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02364986
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Germany

Contacts

• Name: Marcus Müller, PD Dr.
• Affiliation: Department of Neurology University Hospital Bonn

• Name: Verena Dykstra, Dr.

Key inclusion & exclusion criteria

Inclusion Criteria:

- Voluntary participation in this study as proven by written informed consent

- Female or male patients with relapsing remitting MS according to McDon-ald-criteria
(2010 revision) and decision for IFN-b treatment according to routine clinical
criteria (not applying for healthy volunteers)

- Expanded Disability Status Scale (EDSS) between 0.0 and 6.0 (not applying for healthy
volunteers)

- Naïve for IFN-b therapy (not applying for RRMS patients already under treatment)

- Age between 18 and 65 years

- Ability to follow study instructions and likely to attend and complete all required
visits

- Adequate organ function as described below:

- Adequate bone marrow reserve:

- White blood cell (WBC) count = 3000/µl,

- granulocyte count > 1500/µl,

- platelets = 100000/µl,

- haemoglobin = 10 g/dl

- Adequate liver function

- bilirubin < 1.5 times above upper limit of normal range (ULN) (the higher
concentrations are only allowed for patients with RRMS)

- alanine transaminase (ALT/SGPT) and aspartate transaminase (AST/SGOT) < 3
times ULN (the higher concentrations are only allowed for patients with
RRMS)

- Adequate renal function: creatinine < 1.5 times ULN (the higher concentrations
are only allowed for patients with RRMS)

- TSH within normal limits

- Adequate blood clotting:

- INR and PTT within normal limits

- Male and female patients with reproductive potential must use an approved
contraceptive method during and for 3 months after the trial (Pearl index <1; Oral
hormonal contraception must be used in combination with a barrier device due to
elevated risk of nausea. Use of an intrauterine device made of copper is not allowed
for healthy volunteers due to MRI)

- Pre-menopausal female patients with childbearing potential: a negative serum
pregnancy test must be obtained prior to treatment start

- MRI study: only healthy participants

Exclusion Criteria:

- Subjects not able to give consent

- Subject without legal capacity who is unable to understand the nature, scope,
significance and consequences of this clinical trial

- Patients suffering from a form other than relapsing remitting Multiple Sclerosis (not
applying for healthy volunteers)

- Patients with a MS relapse within 30 days before study inclusion

- EDSS >6.0 (not applying for healthy volunteers)

- Patients with known allergy or hypersensitivity to Interferon-beta or ingredients of
the injection solution

- Subjects with a physical or psychiatric condition/ a systemic disease which at the
investigator's discretion may compromise safety of the subject, may confound the
trial results, may interfere with the subject's participation in this clinical trial
or may prevent sufficient compliance

- Known or persistent abuse of medication, drugs or alcohol

- Prior malignancy (unless adequately treated carcinoma in situ of the cervix or
nonmelanoma skin cancer). If prior malignancy was diagnosed and definitively treated
at least 5 years previously with no subsequent evidence of recurrence the subject can
be enrolled at the discretion of the investigator

- Prior chemotherapy, systemic or local treatment with DNA-damaging and
immune-modulating agents, tyrosine kinase inhibitors or anti-angiogenic agents for
any cancer

- History of major depression, suicide attempt in the past, ongoing suicidal thoughts

- Cardiac insufficiency (NYHA III or IV), cardiomyopathy, significant cardiac
dysrhythmia, unstable or advanced ischemic heart disease, or significant hypertension
at rest (BP > 180/110 mmHg)

- HIV, Hepatitis B or C infection or any relevant infectious disease which might
interfere with the study procedures and results (at the discretion of the
investigator)

- Women who are pregnant or breast-feeding

- Comedication with corticosteroids

- Female Patients with reproductive potential who do not accept to use contraception
during the trial and 3 months thereafter

- Treatment in another clinical trial with therapeutic intervention or use of any other
investigational medicinal product (IMP) during the trial or within the 30 days but at
least 5 times the half life of the IMP before enrolment

- Very poor peripheral veins and pronounced fear of blood drawings

- Patients with history of epileptic seizures and / or under medical therapy with
antiepileptic drugs

- MRI study: Metal implants (eg pacemaker, inner-ear prosthesis, nerve stimulator,
implanted defibrillator, infusion pump, artificial joints), wearing of magnetic or
metallic objects that cannot be removed from the body (such as body piercing, dental
prosthesis, implanted electrodes, contraceptive coil, acupuncture needle), tattoos &
permanent makeup, claustrophobia, tinnitus, inability to lie on the back for an
extended period of time, previous surgery on heart or head



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Relapsing-remitting Multiple Sclerosis

Intervention(s)

Drug: Avonex

Drug: Rebif®

Primary Outcome(s)

Change of mRNA (IFN-b, CXCL10, IL-6, MxA and 5'-3'OAS) and protein expression (IFN-b, CXCL10, IL-6) in peripheral blood mononuclear cells/ serum [Time Frame: before / after 1hr / 6 hrs / 12 hrs / 24 hrs]

Secondary Outcome(s)

MRI: Changes in regional cerebral blood flow at rest (arterial spin labeling) and their correlation with psychometric outcome variables and with transcriptome data [Time Frame: before / day 9]

Correlation of Rebif/Avonex side effects in patients with RRMS and healthy volunteers with changes in IFN-b, CXCL10, MxA, 5'-3'OAS, IL-6 serum levels, gene- and miRNA expression pattern and functional immune tests [Time Frame: day 1 (+1 hr / 6hrs /12 hrs after 1. Rebif/Avonex application)]

Changes of IFN-b, CXCL10, MxA, 5'-3'OAS, IL-6 serum levels, gene- and miRNA-expression pattern and functional immune tests between healthy volunteers, RRMS-patients naïve to IFN-b and RRMS-patients with established IFN-b treatment [Time Frame: before / after 1hr / 6 hrs / 12 hrs / 24 hrs]

Correlation of Rebif/Avonex side effects in patients with RRMS and healthy volunteers with changes in IFN-b, CXCL10, MxA, 5'-3'OAS, IL-6 serum levels, gene- and miRNA expression pattern and functional immune tests [Time Frame: day 3 (48 hrs after 1.Rebif/Avonex application)]

Correlation of Rebif/Avonex side effects in patients with RRMS and healthy volunteers with changes in IFN-b, CXCL10, MxA, 5'-3'OAS, IL-6 serum levels, gene- and miRNA expression pattern and functional immune tests [Time Frame: day 9 (24 hrs after 4. Rebif/ 2. Avonex application)]

Change of mRNA and miRNA expression in peripheral blood mononuclear cells and serum in healthy volunteers as well as in patients with RRMS [Time Frame: before / after 1hr / 6 hrs / 12 hrs / 24 hrs]

Correlation of Rebif/Avonex side effects in patients with RRMS and healthy volunteers with changes in IFN-b, CXCL10, MxA, 5'-3'OAS, IL-6 serum levels, gene- and miRNA expression pattern and functional immune tests [Time Frame: day 8 (72 hrs after 3. Rebif application, +1 hr / 6hrs /12 hrs after 4. Rebif/ 2. Avonex application)]

Psychometric testing: correlation between Rebif/Avonex administration and scores in depression and anxiety scales [Time Frame: before / day 9]

Changes in functional neuroimaging endophenotypes in the limbic system or prefrontal cortex that constitute possible markers of anxiety and depression and their correlation with psychometric outcome variables [Time Frame: before / day 9]

Correlation of Rebif/Avonex side effects in patients with RRMS and healthy volunteers with changes in IFN-b, CXCL10, MxA, 5'-3'OAS, IL-6 serum levels, gene- and miRNA expression pattern and functional immune tests [Time Frame: day 2 (24 hrs after 1.Rebif/Avonex application)]

Correlation of Rebif/Avonex side effects in patients with RRMS and healthy volunteers with changes in IFN-b, CXCL10, MxA, 5'-3'OAS, IL-6 serum levels, gene- and miRNA expression pattern and functional immune tests [Time Frame: day 5 (48 hrs after 2.Rebif/ 96 hrs after 1. Avonex application)]

Secondary ID(s)

NEU-201201-RESI

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

BfARM, Bonn

DZNE, Bonn