Diffuse systemic sclerosis Scleroderma Systemic sclerosis (SSc)
Conditions
Interventions
Patients meeting all eligibility criteria will have a baseline skin biopsy (2 x
3mm punch biopsies) taken before being randomised 1:1:1 to FT011 200mg, FT011
400mg, or placebo.
Participants will ta
Sponsors
Certa Therapeutics Pty Ltd
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Participants must meet all the following criteria: • Provide written informed consent prior to any study procedures and who agree to adhere to all protocol requirements. • Aged 18 to 75 years inclusive at the time of consent. • Have a classification of systemic sclerosis, as defined by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria with disease duration =15 to =50% of predicted at Screening. • If on azathioprine, mycophenolate mofetil, or hydroxychloroquine, have been on a stable dose for at least 2 months prior to baseline. • Participants must agree to use contraception according to protocol section 5.4.4.
Exclusion criteria
Exclusion criteria: Participants must not meet any of the following criteria: • Pregnant or breast-feeding, or plan to become pregnant during the study. • Have received any IMP within 30 days or 5 half-lives prior to randomisation (4 months if the previous drug was a new chemical entity), whichever is longer. • Have known or suspected contraindications to the IMP. • Have severe or unstable SSc or end-stage organ involvement as evidenced by: o On an organ transplantation list or has received an organ transplant including autologous stem cell transplant. o Renal crisis within 1 year prior to Baseline. • Interstitial lung disease or pulmonary hypertension requiring constant oxygen therapy. This excludes oxygen used to aid sleep or exercise. • Gastrointestinal dysmotility requiring total parenteral nutrition or requiring hospitalisation within the 6 months prior to Baseline. • Concomitant inflammatory myositis, rheumatoid arthritis, or systemic lupus erythematosus when definite classification criteria for those diseases are met (Bohan and Peter criteria for polymyositis and dermatomyositis) • SSc-like illnesses related to exposures or ingestions • The use of the following drugs within the specified periods: o Methotrexate in the 2 weeks prior to Day 1 o Other anti-fibrotic agents including D-penicillamine or tyrosine kinase inhibitors (nilotinib, imatinib, dasatinib) in the month prior to Screening. o Biologic drugs such as tumour necrosing factor (TNF) inhibitors, tocilizumab, or Janus kinase (JAK) inhibitors, in the 3 months prior to Screening. o Rituximab in the 6 months prior to Screening. o Cyclophosphamide oral or intravenous (IV) in the 3 months prior to Screening. o Oral prednisolone >10 mg per day or IV steroids in the month prior to Screening. • Have any malignancy not considered cured (except basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix); a subject is considered cured if there has been no evidence of cancer recurrence for the 6 years prior to randomisation. • Have aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), or bilirubin values above the upper limit of normal (ULN) at Screening or Baseline, or evidence of hepatic disease as determined by any one of the following: history of hepatic encephalopathy, history of oesophageal varices, or history of portacaval shunt. • Estimated glomerular filtration rate (eGFR)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Outcome Measures • FT011 maximum concentration (cmax), time to maximum concentration (tmax), and area under the curve (AUC) in plasma after a single dose and after 12-weeks of treatment. • Measurement of steady state FT011 levels in plasma. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Outcome Measures Safety will be assessed by: • Treatment emergent adverse events from first dose of study drug to End of Study • Physical examination • Vital signs (blood pressure, heart rate, respiratory rate, and temperature) • 12-lead electrocardiograms (ECG) • Safety laboratory results (haematology, biochemistry, coagulation, and urinalysis) • Use of concomitant medications Efficacy will be measured by: Change in mRSS from Baseline at each visit. • Change in percent predicted FVC from Baseline to Week 4, Week 8, and Week 12. • Change in SHAQ-DI Score from Baseline to Week 4, Week 8, and Week 12. • Change in Patient Global Assessment Score from Baseline to Week 4, Week 8, and Week 12. • Change in Physician Global Assessment Score from Baseline to Week 4, Week 8, and Week 12. • The proportion of patients showing an improvement (defined as ACR Composite Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) score predicted probability of >=0.60) at Week 12. • Change in the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI) score from Baseline to Week 12. • Change in the 5-D Itch Scale from Baseline to Week 12. Exploratory • A histological analysis of skin biopsy samples before and after 12 weeks of treatment, looking at cellular markers of inflammation and fibrosis, and target localisation. • Measurement, by computational biology, of the molecular markers of inflammatory and fibrotic signalling pathways in skin biopsy samples before and after 12 weeks of treatment, using techniques of whole tissue or single cell sorting and subsequent ribonucleic acid (RNA) analysis (scRNA-seq). • Measurement of plasma and serum cytokines and chemokines before and after 12 weeks of treatment, and investigation of how the participant*s peripheral immune system responds to specific stimulus by measurement of immune cell activation markers | — |
Countries
Netherlands
Outcome results
None listed