SIZOMUS Safety of Ixazomib Targeting Plasma Cells in Multiple Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03783416
• Date of registration: 10/12/2018
• Prospective Registration: Yes
• Primary sponsor: Queen Mary University of London
• Public title: SIZOMUS Safety of Ixazomib Targeting Plasma Cells in Multiple Sclerosis SIZOMUS
• Scientific title: Safety of Ixazomib Targeting Plasma Cells in Multiple Sclerosis: A Phase 1b Randomised, Double-blind, Placebo-controlled Trial.
• Date of first enrolment: June 1, 2019
• Target sample size: 72
• Recruitment status: Not yet recruiting
• URL: https://clinicaltrials.gov/show/NCT03783416
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Contacts

• Name: Sharmilee Gnanapavan, MD

Key inclusion & exclusion criteria

Inclusion Criteria:

- Each participant must meet all of the following inclusion criteria to be enrolled in the
study:

1. Male and female patients 18 to 65 years old at screening

2. Must have a diagnosis of MS, and:

- Patients with RRMS must be on DMT

- Patients with progressive MS must not be on DMT

3. Participants with RRMS must be on stable DMT (i.e. must not have had a relapse within
1 month prior to the screening visit). Patients on tecfidera, cladribine, ocrelizumab,
alemtuzumab, fingolimod or natalizumab must be enrolled with caution, at Chief
Investigator's (CI) discretion because of the lymphopenia caused by these drugs and
the risk of thrombocytopenia in 1-2 % of people after alemtuzumab

4. OCB positive CSF either from a previous CSF analysis or from the screening CSF
analysis

5. Able and willing to give written informed consent and comply with protocol
requirements with the understanding that consent may be withdrawn by the patient at
any time without prejudice to future medical care.

6. Agree to the use of effective contraception as follows:

Female patients must:

- Be postmenopausal for at least 1 year before the screening visit (postmenopausal
status confirmed by serum Follicle Stimulating Hormone (FSH) and oestrogen levels
at screening or from a historical sample), OR

- Surgically sterile, OR

- If they are of childbearing potential, must agree to practice two effective
methods of contraception concurrently from the time of signing the informed
consent form until 90 days after the last dose of study drug, OR

- Agree to practice true abstinence when this is in line with the preferred and
usual lifestyle of the subject. Periodic abstinence e.g. calendar, ovulation,
symptothermal, post-ovulation methods and withdrawal are not acceptable methods
of contraception

Male patients must:

- Even if surgically sterilized (post-vasectomy with documentation of azoospermia),
agree to practice effective barrier contraception during the entire study
treatment period and through to 90 days after the last dose of study drug, OR

- Agree to practice true abstinence when this is in line with the preferred and
usual lifestyle of the subject. Periodic abstinence e.g. calendar, ovulation,
symptothermal, post-ovulation methods and withdrawal are not acceptable methods
of contraception

7. Clinical laboratory values:

1. Absolute neutrophil count (ANC) = 1 x 109/L

2. Platelet count = 100 x 109/L

3. Total bilirubin = 1.5 × the upper limit of the normal range (ULN)

4. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) = 3 × ULN.

5. Calculated creatinine clearance = 30 mL/min

Exclusion Criteria:

- Participants meeting any of the following exclusion criteria are not to be enrolled in
the study:

1. EDSS > 8.5 at screening

2. MS relapse within 1 month prior to screening

3. Female patients who are lactating or have a positive serum pregnancy test at
screening

4. Major surgery within 14 days before baseline

5. Any clinically relevant malignancy or infection, as per CI/PI (or delegate)
decision, including a possible diagnosis of multiple myeloma: raised erythrocyte
sedimentation rate (ESR) and positive urine Bence Jones protein at screening

6. Infection requiring systemic (intravenous) antibiotic therapy or other serious
infection within 14 days before study enrolment. Urinary tract infections (UTIs)
will be treated prior to baseline and may delay baseline

7. Evidence of current uncontrolled cardiovascular conditions, including
uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic
congestive heart failure, unstable angina, or myocardial infarction within 6
months of screening

8. Systemic treatment, within 14 days before the first dose of ixazomib, with strong
Cytochrome P450 Isoform 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin,
carbamazepine, phenytoin, phenobarbital), or use of St. John's Wort

9. History of active hepatitis B or C virus infection, or human immunodeficiency
virus (HIV) positive or positive Tuberculin (TB) ELISPOT. If there is positive TB
ELISPOT and the TB team decides to treat as latent TB, participants can be
reassessed for inclusion after treatment

10. Any serious medical or psychiatric illness that could, in the investigator's
opinion, potentially interfere with the completion of treatment according to this
protocol

11. Known GI disease or GI procedure that could interfere with the oral absorption or
tolerance of ixazomib including difficulty swallowing

12. Diagnosed or treated for malignancy within 2 years before study enrolment or
previously diagnosed with another malignancy and have any evidence of residual
disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type
are not excluded if they have undergone complete resection

13. Patient has = Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical
examination during the screening period

14. Participation in other clinical trials involving investigational (unlicensed)
medicinal products, licensed medicinal products or alternative medicinal
therapies, within 30 days of screening and throughout the duration of this trial.
Participation in non-interventional, questionnaire or observational studies
whilst enrolled in this study is permitted.

15. Patients that have previously been treated with ixazomib or participated in a
study with ixazomib whether treated with ixazomib or placebo

16. Known allergy to any of the study medications, their analogues, or excipients in
the various formulations of any agent

17. Any pre-existing central nervous system disease or involvement other than MS

18. History of uncontrolled drug or alcohol abuse within 6 months prior to screening.



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

Health Condition(s) or Problem(s) studied

Relapsing Remitting Multiple Sclerosis

Secondary Progressive Multiple Sclerosis

Primary Progressive Multiple Sclerosis

Intervention(s)

Drug: Ixazomib (NINLARO®) capsules / Matching placebo capsules

Primary Outcome(s)

Safety - Adverse events (AE) will be compared between active and placebo arm [Time Frame: Baseline to 24 months]

Efficacy - the proportion of OCB IgG negative subjects will be compared between active and placebo arm [Time Frame: Baseline to 24 months]

Secondary Outcome(s)

Change In Expanded Disability Status Scale (EDSS) with Ixazomib versus placebo arm at 24 months. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist [Time Frame: Baseline to 24 months]

Magnetic Resonance Imaging (MRI) [Time Frame: Baseline to 24 months]

Secondary ID(s)

2018-003686-34

012436

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Takeda Pharmaceuticals International, Inc.