Randomized, double-blind, placebo-controlled, 3-arm, 36 weeks parallel-group study to evaluate the safety and tolerability of ORY-2001 in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS)

• Register: EUCTR
• Last refreshed on: 13 November 2017
• Main ID: EUCTR2017-002838-23-ES
• Date of registration: 21/07/2017
• Prospective Registration: Yes
• Primary sponsor: Oryzon Genomics S. A
• Public title: Randomized, double-blind, placebo-controlled, 3-arm, 36 weeks parallel-group study to evaluate the safety and tolerability of ORY-2001 in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS)
• Scientific title: Randomized, double-blind, placebo-controlled, 3-arm, 36 weeks parallel-group study to evaluate the safety and tolerability of ORY-2001 in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS)
• Date of first enrolment: 27/10/2017
• Target sample size: 24
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002838-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: Laia Torruella
• Affiliation: Trial Form Support

• Name: Laia Torruella
• Affiliation: Trial Form Support

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients aged 18-65 years, inclusive
2. Diagnosis of MS (McDonald Criteria 2010)
3. Relapsing-Remitting or Secondary Progressive MS phenotypes
4. Active MS within the previous 12 months, defined as:
a. At least one relapse, or
b. At least one T1 Gadolinium (Gd)-enhancing lesion*, or
c. At least one new or enlarging T2 lesion*
* Subjects without evidence of active MS in the last 12 months can be included if at least one of these two criteria are fulfilled at the screening MRI performed up to 7 days prior to randomization
5. Expanded Disability Status Scale (EDSS) at screening and baseline visit between 0 and 6.5
6. Fertile male and female must use highly efficient contraception from Screening visit until the last treatment day (including open-label period), defined as:
i. A method with less than 1% failure rate (e.g. permanent sterilisation, hormone implants, hormone injections, some intrauterine devices, or vasectomised partner)
OR
ii. The use of two methods of contraception (e.g. one barrier method [condom, diaphragm or cervical/vault caps] with spermicide and one hormonal contraceptive [e.g. combined oral contraceptives, patch, vaginal ring, injectables and implants])
7. Patient must sign and date a written informed consent prior to entering the study
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Previous history of central nervous system (CNS) or psychiatric clinical disease that according to the investigator might confound the assessment of the study endpoints
2. CNS or psychiatric current therapies specifically anti-depressants as tranylcypromine or phenelzine and Monoamine Oxidase (MAO) therapies
3. Cancer history or cancer therapies that according to the investigator might confound the assessment of the study endpoints
4. Patients with uncontrolled hypertension (uncontrolled in the opinion of the investigator), and diabetes (consistent glucose level >100 mg/dL) or hepatitis (persistent liver inflammation)
5. Inter-current illness or social situation that will limit compliance with study requirements
6. MS relapse in the 6 weeks prior to randomization
7. Treatment with any investigational medicinal product within twelve weeks prior to randomization or 5 half-lives, whichever is longer
8. Treatment with interferon beta or glatiramer acetate in the four weeks prior to randomization
9. Treatment with fingolimod or dimethyl fumarate in the twelve weeks prior to randomization
10. Treatment with azathioprine or methotrexate in the 6 months prior to randomization
11. Treatment with teriflunomide in the previous year unless a successful wash-out procedure has been performed (plasmatic levels below 0.02 mg/l) prior to randomization
12. Treatment with natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribine, mitoxantrone or cyclophosphamide in the year prior to randomization
13. Concomitant treatment with known MAO inhibitors (as rasagiline) or with other drugs with known incompatibility with MAO inhibitors or contraindications to receive MAO inhibitors
14. A known history of hypersensitivity to Gd
15. Participation in another clinical trial with an investigational drug product not completed within the 30 days prior to enrolment
16. Abnormal or clinically relevant haematology and biochemistry laboratory tests values (including kidney function profile)
17. Abnormal clinical evaluation
18. Abnormal or clinically relevant electrocardiogram (ECG) findings
19. Positive tuberculosis, human immunodeficiency virus (HIV), hepatitis C or hepatitis B (Hepatitis B surface antigen [HbsAg]) serology (test performed at screening)
20. Pregnancy or breast feeding
21. History of alcohol or substance abuse


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

patients with Relapsing-Remitting Multiple Sclerosis (RRMS) and Secondary Progressive Multiple Sclerosis (SPMS)
MedDRA version: 20.0 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: ORY2001
Product Code: ORY2001
Pharmaceutical Form: Capsule
INN or Proposed INN: Not yet requested
Current Sponsor code: ORY2001
Other descriptive name: PHENYLCYCLOPROPYLAMINE DERIVATIVES AND DUAL LSD1/MAO-B (LYSINE-SPECIFIC DEMETHYLASE 1 AND MONOAMINE OXIDASE-B) INHIBITOR
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 0.6-1.2
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): • Number, frequency and severity of Adverse Events (AEs).
• Number, frequency and severity of Serious Adverse Events (SAEs)
• Number and percentage of withdrawn patients due to AEs
• Change from baseline in physical examination, vital signs and ECG parameters
• Frequency of physical examination parameters, vital signs and ECG parameters of potential clinical concern
• Change from baseline in clinical laboratory parameters (hematology, clinical chemistry and urinalysis)
• Frequency of clinical laboratory parameters (hematology, clinical chemistry and urinalysis) of potential clinical concern
• Use of concomitant medication

Secondary Objective: To assess the effect of two doses of ORY-2001 on inflammatory Magnetic Resonance Imaging (MRI) measures compared to placebo in MS subjects.

Main Objective: To evaluate the safety and tolerability of two doses of ORY-2001 compared to placebo in multiple sclerosis (MS) subjects.

Timepoint(s) of evaluation of this end point: End points will be evaluated at the end of study vs the baseline values.

Secondary Outcome(s)

Secondary end point(s): • Cumulative number of Combined Unique Active lesions (CUAL) (defined as Gd-enhancing T1-weighted lesions and non-enhancing new/enlarging T2-weighted lesions) at weeks 8, 12, 24, 32 and 36 as assessed through MRI.

Timepoint(s) of evaluation of this end point: at weeks 8, 12, 24, 32 and 36

Secondary ID(s)

CL02-ORY-2001MS

Source(s) of Monetary Support

Oryzon Genomics S.A.