| Eligibility |
Inclusion Criteria:
- A diagnosis of systemic sclerosis based on the 2013 ACR-EULAR Classification Criteria
for SSc with a disease duration of =7 years as defined by the date of onset of the
first non-Raynaud's symptom. Systemic sclerosis may be of limited or diffuse type.
- A serum level of CCL24 =400 pg/mL at Screening
- Presence of one of the below confirming active disease at Screening:
a. Skin involvement with mRSS =15 b. Presence of interstitial lung disease at
Screening, evidenced by >10% involvement at HRCT (historic HRCT performed within 12
weeks of Screening may be used if the images are available to be sent to the central
reader) and at least one of the following at Screening: i. C-reactive protein (CRP) =6
mg/L, or ii. Erythrocyte sedimentation rate (ESR) =28 mm/hr, or iii. Platelet count
=(330,000/microliter), or iv. Serum level of CCL24 =1,000 pg/mL c. Current digital
ulcer and at least one of the following at Screening: i. CRP =6 mg/L, or ii. ESR =28
mm/hr, or iii. Platelet count =330,000/µL), or iv. Serum level of CCL24 =1,000 pg/mL
- If under active immunosuppressive treatment for SSc, treatment must be stable
=12 weeks before Screening with intention to continue with no change in dose from
Screening through the end of study. Hydroxychloroquine (or similar antimalarial such
as chloroquine) use is allowed and may be combined with up to one of the following:
1. Methotrexate (maximum dose 25 mg/week),
2. Azathioprine (maximum dose 200 mg/day),
3. Mycophenolate mofetil (MMF)/mycophenolic acid (MPA) (maximum dose 2 g/dayMMF or
equivalent).
- Oral corticosteroids of prednisone (or equivalent) =10 mg/day are allowed but not
required and if present, must be stable for 30 days prior to Screening.
- If under treatment with the following, treatment must be stable for =8 weeks before
Screening with the intention to continue with no change in dose from Screening through
the end of study:
1. Endothelin receptor antagonist, such as macitentan, bosentan, ambrisentan
2. Phosphodiesterase type 5 inhibitors, such as sildenafil and tadalafil.
- Negative serum pregnancy test for biologically female patients of childbearing
potential
- Men and women with reproductive potential are required to use a highly effective means
of contraception through the course of the study
Exclusion Criteria:
1. Systemic sclerosis-like illness associated with environmental or ingested agents such
as toxic rapeseed oil, vinyl chloride, or bleomycin.
2. Rheumatic autoimmune disease other than SSc, including but not limited to rheumatoid
arthritis, systemic lupus erythematosus, undifferentiated connective tissue disorder,
polymyositis, dermatomyositis, eosinophilic fasciitis, primary Sjögren's syndrome, and
eosinophilic myalgia syndrome when classification or diagnostic criteria for those
diseases are met.
3. Systemic sclerosis with end-stage organ involvement at Screening, including:
1. Currently or anticipating placement on an organ transplantation list, or has
received an organ transplant
2. Renal crisis within 6 months before Screening
3. Interstitial lung disease with FVC% < 45 or requiring constant oxygen therapy.
Oxygen used to aid sleep or exercise is allowed.
4. Pulmonary hypertension requiring constant oxygen therapy or continuous
intravenous treatment with prostaglandins. Oxygen used to aid sleep or exercise
is allowed.
5. Gastrointestinal dysmotility requiring total parenteral nutrition or
hospitalization within 6 months before Screening.
4. Use of following treatment(s) during the study or within the times noted:
1. Within 26 weeks prior to Screening: cyclophosphamide, rituximab
2. Within 12 weeks prior to Screening: tocilizumab, thalidomide, cyclosporine,
pirfenidone, or tyrosine kinase inhibitors (e.g., nintedanib)
3. Within 6 weeks prior to Screening: ultraviolet (UV) phototherapy
4. Within 30 days prior to Screening: systemic corticosteroids at doses greater than
10mg/day prednisone or equivalent
5. Other monoclonal antibodies not listed, please consult with the Medical Monitor
regarding appropriate discontinuation period
5. Anticipated to require the following treatments during the study: cell depleting
therapy, chlorambucil, total lymphoid radiation, anti-thymocyte globulin,
plasmapheresis, extra-corporeal photopheresis or bone marrow transplant. If prior use,
consult Medical Monitor.
6. Participation in another research study of an investigational drug or device within 10
weeks of Screening or received treatment with any investigational agent within 30 days
or 5 elimination half-lives (whichever is longer) of the investigational drug prior to
Screening.
7. Prior exposure to CM-101
8. Any major surgery (including joint surgery) within 8 weeks prior to Screening or have
surgery scheduled during the study duration.
9. Receipt of a live/attenuated vaccine within 10 days of study Screening.
10. Cancer, history of cancer or lymphoproliferative disorder within the previous 5 years
(other than adequately treated nonmetastatic basal cell skin cancer or squamous cell
skin cancer that has not recurred for at least 1 year prior to Screening; history of
cervical carcinoma in situ that has been adequately treated and that has not recurred
for at least 3 years prior to Screening).
11. Concurrent serious medical condition which, in the opinion of the Investigator, makes
the patient inappropriate for this study such as but not limited to poorly controlled
chronic heart failure, clinically meaningful arrhythmia, severe pulmonary or systemic
hypertension, hepatic impairment, poorly controlled diabetes, unstable atherosclerotic
cardiovascular disease, or severe peripheral vascular disease.
12. Any clinically significant disease or laboratory abnormality at Screening which may
interfere with the study evaluation and/or safety of the patient including the
following:
1. hemoglobin <9 g/dL
2. absolute neutrophils <1.0 × 10-9/L
3. white blood cells (WBC) <3,000/mm3
4. platelets <100,000/mm3
5. alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2× upper
limit of normal (ULN)
6. total bilirubin >1.5× ULN.
13. History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV), or a
previously positive result for hepatitis B surface antigen (HBsAg), anti-hepatitis C
virus (HCV), or anti-HIV 1 or 2. Local testing may be performed based on Investigator
judgment if there are no historical values or there is an indication for testing.
14. Known active bacterial, viral, fungal, mycobacterial, or other systemic infection
including any infected ulcer(s); or any major episode of infection requiring
hospitalization or treatment with IV antimicrobials within 8 weeks of Screening; or
any infection requiring antibiotic therapy within 2 weeks of Screening.
15. History of severe allergic or anaphylactic reactions to human, humanized, or murine
monoclonal antibodies.
16. Currently pregnant or breastfeeding at entry into this study.
17. History of severe depression, psychosis, or suicidal ideation, or a history of alcohol
abuse or drug addiction.
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