FT011 for Scleroderma

• Register: EUCTR
• Last refreshed on: 30 August 2021
• Main ID: EUCTR2020-005116-21-ES
• Date of registration: 22/07/2021
• Prospective Registration: Yes
• Primary sponsor: Certa Therapeutics Pty Ltd
• Public title: FT011 for Scleroderma
• Scientific title: A phase II, randomised, double blind, placebo-controlled study of the pharmacokinetics, pharmacodynamic effects, and safety, of oral FT011 in participants with diffuse systemic sclerosis - FT011 for scleroderma
• Date of first enrolment: 22/07/2021
• Target sample size: 30
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-005116-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Netherlands, Poland, Russian Federation, Spain, Ukraine

Contacts

• Name: Coordinadora Nacional
• Affiliation: Dra. Carmen Pilar Simeon Aznar

• Name: Coordinadora Nacional
• Affiliation: Dra. Carmen Pilar Simeon Aznar

Key inclusion & exclusion 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 =5 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

diffuse systemic sclerosis
MedDRA version: 21.0 Level: LLT Classification code 10012977 Term: Diffuse systemic sclerosis System Organ Class: 100000004859

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Name: FT011 100 mg
Product Code: FT011
Pharmaceutical Form: Capsule
INN or Proposed INN: None yet
CAS Number: 1001288-58-9
Current Sponsor code: FT011
Other descriptive name: 2-(((2E)-3-(3-methoxy-4-(2-propyn-1-yloxy)phenyl)-1-oxo-2-propen-1-yl)amino)benzoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: FT011 200 mg
Product Code: FT011
Pharmaceutical Form: Capsule
INN or Proposed INN: None yet
CAS Number: 1001288-58-9
Current Sponsor code: FT011
Other descriptive name: 2-(((2E)-3-(3-methoxy-4-(2-propyn-1-yloxy)phenyl)-1-oxo-2-propen-1-yl)amino)benzoic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

Secondary Objective: 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.

Main Objective: To assess the PK of oral FT011 in participants with diffuse SSc

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.

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: Timepoints are described in the endpoints in E.5.2

Secondary ID(s)

CER-FT011-SSc01

NCT04647890

Source(s) of Monetary Support

Certa Therapeutics Pty Ltd

Ethics review

Status: Approved
Approval date: 14/07/2021
Contact: