E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diffuse systemic sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Diffuse systemic sclerosis, commonly called scleroderma. Scleroderma is a rare autoimmune disease that causes thickening and hardening (fibrosis) of the skin and other organs. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012977 |
E.1.2 | Term | Diffuse systemic sclerosis |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the PK of oral FT011 in participants with diffuse SSc |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of oral FT011 compared to placebo in participants with diffuse SSc.
To evaluate the short-term efficacy of oral FT011 compared to placebo in improving disease activity in participants with diffuse SSc. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. Participants must agree to use contraception according to protocol section 5.4.4. |
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E.4 | Principal 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: a. On an organ transplantation list or has received an organ transplant including autologous stem cell transplant. b. 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: a. Methotrexate in the 2 weeks prior to Day 1 b. Other anti-fibrotic agents including D-penicillamine or tyrosine kinase inhibitors (nilotinib, imatinib, dasatinib) in the month prior to Screening. c. Biologic drugs such as tumour necrosing factor (TNF) inhibitors, tocilizumab, or Janus kinase (JAK) inhibitors, in the 3 months prior to Screening. d. Rituximab in the 6 months prior to Screening. e. Cyclophosphamide oral or IV in the 3 months prior to Screening. f. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• FT011 cmax, tmax, and AUC in plasma after a single dose and after 12-weeks of treatment. • Measurement of steady state FT011 levels in plasma.
Additional calculations may be performed, and metabolites may also be measured. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
FT011 cmax, tmax, and AUC in plasma after a single dose on day 1 and after last dose at week 12 Steady state concentrations will be at the 1, 2, and 3 month pre-dose timepoints |
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E.5.2 | Secondary end point(s) |
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 ECG. • Safety laboratory results (haematology, biochemistry, coagulation, and urinalysis). • Use of concomitant medications.
Efficacy Endpoints • 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 HAQ-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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoints are described in the endpoints in E.5.2 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Poland |
Netherlands |
Spain |
Russian Federation |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as the last protocol-specified data available from the last participant in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 13 |