Primary objective: To assess the PK of oral FT011 in participants with diffuse SSc.Secondary objectives: • To assess the safety and tolerability of oral FT011 compared to placebo in participants with diffuse SSc.• To evaluate the short-term efficacy…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Diffuse systemic sclerosis
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
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 outcome
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
Background summary
Systemic sclerosis (SSc) is a rare and complex autoimmune disease,
characterised by vascular damage, chronic inflammation, and fibrosis of the
skin and internal organs. The current treatment recommendations include the
use of immunosuppressants, such as methotrexate, mycophenolate mofetil, and
cyclophosphamide, for managing the symptoms and preventing complications in SSc
patients1. However, these treatments have poor efficacy and are associated
with significant side effects, such as organ toxicities and serious
infections. Nintedanib, a multiple tyrosine kinase inhibitor recently approved
for the treatment of systemic sclerosis-associated interstitial lung disease
(SSc-ILD), slowed the rate of decline in lung function in SSc-ILD2. Since no
clinical benefit of nintedanib was observed for other manifestations of the
disease, there remains an unmet need for safe and effective treatments in early
diffuse SSc patients.
Study objective
Primary objective: To assess the PK of oral FT011 in participants with diffuse
SSc.
Secondary objectives:
• 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.
Study design
This is a multi-centre, randomised, double blind, placebo-controlled study to
assess the pharmacokinetic pharmacodynamic effects and safety of FT011 in
participants with diffuse systemic sclerosis.
Intervention
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 take their investigational medicinal product (IMP) once a day
for 3 months (12 weeks), in addition to their standard-of-care scleroderma
medications.
Study burden and risks
Participating in the study can have advantages and disadvantages. The study
drug may cause a reduction in some of the scleroderma symptoms, but this is not
certain. It is also possible that patient's/ participant's condition could get
worse at any time during this study.
Participating in the study can have the following disadvantages:
- Patient/ Participant may experience side effects or adverse effects of the
study drug.
- Patient/ Participant may suffer from the measurements during the study. For
example: a blood draw can be painful. Or patient/ participant could get
bruising as a result.
- Participating in the study costs you extra time.
- Patient/ Participant must be admitted to the hospital. Or longer than usual.
- Patient/ Participant must adhere to the agreements associated with the study.
- The questionnaires can be confronting.
- Patient/ Participant must adhere to strict rules about taking drugs.
- There could be disadvantages for the patient's/ participant's partner or
housemate.
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Melbourne VIC 3000
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Level 9, 31 Queen Street Level 9, 31 Queen Street
Melbourne VIC 3000
AU
Listed location countries
Age
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 <=5 years from first non-Raynaud phenomenon manifestation.
• 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.
• Have skin thickening in a body area suitable for repeat biopsy.
• Have a mRSS at Screening of >=15 to <=40.
• FVC >=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
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) <60mL/min, urinary
albumin/creatinine ratio <30mg/g.
• Haemoglobin < 80 g/L, platelets < 90 x 109/L, or neutrophil count < 1.4 x
109/L
• 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-005116-21-NL |
| ClinicalTrials.gov | NCT04647890 |
| CCMO | NL77724.056.21 |