Clinical trial NCT04647890: Effects of FT011 in Systemic Sclerosis
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis, Systemic
Lead sponsor: Certa Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-12-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: FT011 Levels in Plasma
timeFrame: Mean of cmax post first dose and cmax post last dose
measure: FT011 Levels in Plasma
timeFrame: Mean of time to cmax post first dose and time to cmax post last dose
measure: FT011 Levels in Plasma
timeFrame: Mean of AUC hours post first dose and AUC hours post last dose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From Baseline to End of Study
timeFrame: Baseline to Week 16
measure: mRSS Change From Baseline
timeFrame: End of treatment (week 12)
measure: %FVC Change From Baseline
timeFrame: End of treatment (Week 12)
measure: Physician Global Assessment Change From Baseline
timeFrame: End of treatment (Week 12)
measure: Patient Global Assessment Change From Baseline
timeFrame: End of treatment (Week 12)
measure: Scleroderma HAQ-DI Change From Baseline
timeFrame: End of treatment (Week 12)
measure: Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) at Week 12
timeFrame: Week 12
measure: Scleroderma Clinical Trial Consortium Damage Index (SCTC-DI) Change From Baseline
timeFrame: End of treatment (Week 12)
measure: 5-D Itch Scale Change From Baseline
timeFrame: End of treatment (Week 12)
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Nijmegen
country: Netherlands
facility: Certa SSc trial site
city: Bydgoszcz
country: Poland
facility: Certa SSc trial site
city: Kraków
country: Poland
facility: Certa SSc trial site
city: Malbork
country: Poland
facility: Certa SSc trial site
city: Warsaw
country: Poland
facility: Certa SSc trial site
city: Barcelona
country: Spain
facility: Certa SSc trial site
city: Kyiv
country: Ukraine
facility: Certa SSc trial site
city: Poltava
country: Ukraine
facility: Certa SSc trial site
Study officials:
affiliation: Certa Therapeutics Pty Ltd
name: Darren Kelly, PhD
role: STUDY_DIRECTOR
References: