Effects of FT011 in Systemic Sclerosis
Condition: Scleroderma, Systemic; Scleroderma, Diffuse; Sclerosis, Systemic
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Sclerosis
Intervention: FT011; FT011; Placebo
Intervention description: Two x 100mg capsules once daily for 12 weeks; Two x 200mg capsules once daily for 12 weeks; Two placebo capsules once daily for 12 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      FT011 is an anti-fibrotic drug that is being tested as a treatment for scleroderma. This
      study is being conducted to see what the body does to the drug (pharmacokinetics), and what
      the drug does to the body (pharmacodynamics).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide written informed consent prior to any study procedures and who agree to adhere
             to all protocol requirements.

          2. Aged 18 to 75 years inclusive at the time of consent.

          3. Have a classification of systemic sclerosis, as defined by American College of
             Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria with
             disease duration ≤10 years from first non-Raynaud phenomenon manifestation.

          4. Have a diagnosis of diffuse cutaneous SSc defined as systemic sclerosis with skin
             thickening on the upper arms proximal to the elbows, on the upper legs proximal to the
             knees, or on the trunk.

          5. Have skin thickening in a body area suitable for repeat biopsy.

          6. Have a mRSS at Screening of ≥15 to ≤40.

          7. FVC ≥50% of predicted at Screening.

          8. If on azathioprine, mycophenolate mofetil, or hydroxychloroquine, have been on a
             stable dose for at least 2 months prior to baseline.

          9. Women of childbearing potential (WOCPB) and males with partners of child-bearing
             potential must agree to use highly effective contraception (a failure rate of <1%),
             for the duration of the study and until three months after their last dose of IMP.

        Exclusion Criteria:

          1. Pregnant or breast-feeding, or plan to become pregnant during the study.

          2. 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.

          3. Have known or suspected contraindications to the IMP.

          4. Have severe or unstable SSc or end-stage organ involvement as evidenced by:

               1. On an organ transplantation list or has received an organ transplant including
                  autologous stem cell transplant.

               2. Renal crisis within 1 year prior to Baseline.

          5. Interstitial lung disease or pulmonary hypertension requiring constant oxygen therapy.
             This excludes oxygen used to aid sleep or exercise.

          6. Gastrointestinal dysmotility requiring total parenteral nutrition or requiring
             hospitalisation within the 6 months prior to Baseline.

          7. 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)

          8. SSc-like illnesses related to exposures or ingestions

          9. The use of the following drugs within the specified periods:

               1. Methotrexate in the 2 weeks prior to Day 1

               2. Other anti-fibrotic agents including D-penicillamine or tyrosine kinase
                  inhibitors (nilotinib, imatinib, dasatinib) in the month prior to Screening.

               3. Biologic drugs such as tumour necrosing factor (TNF) inhibitors, tocilizumab, or
                  Janus kinase (JAK) inhibitors, in the 3 months prior to Screening.

               4. Rituximab in the 6 months prior to Screening.

               5. Cyclophosphamide oral or IV in the 3 months prior to Screening.

               6. Oral prednisolone >10 mg per day or IV steroids in the month prior to Screening.

         10. 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.

         11. 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.

         12. Estimated glomerular filtration rate (eGFR) <60mL/min, urinary albumin/creatinine
             ratio >30mg/g.

         13. Haemoglobin < 80 g/L, platelets < 90 x 109/L, or neutrophil count < 1.4 x 109/L

         14. Other than SSc, have any other medical condition or significant co-morbidities,
             clinically relevant social or psychiatric conditions, or any finding during Screening,
             which in the investigator's opinion may put the subject at risk or interfere with the
             study objectives.