|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Focal Segmental Glomerulosclerosis (FSGS)
|Medical condition in easily understood language
|Diseases [C] - Male diseases of the urinary and reproductive systems [C12]
|E.1.2 Medical condition or disease under investigation
|Focal segmental glomerulosclerosis
|System Organ Class
|10038359 - Renal and urinary disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To evaluate the efficacy of PF-06730512 compared to baseline in the reduction of proteinuria following 12 weeks of treatment in patients with FSGS.
|Secondary objectives of the trial
|- To evaluate the safety and tolerability of PF-06730512 following 12 weeks of treatment in subjects with FSGS.
- To evaluate the effects of PF-06730512 on proteinuria time course.
- To summarize complete and partial remission rates following administration of PF-06730512.
- To evaluate the effect of PF-06730512 on renal function.
- To evaluate the serum exposure of PF-06730512 in FSGS patients.
- To evaluate the immunogenicity profile of PF-06730512.
|Trial contains a sub-study
|Principal inclusion criteria
|- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
- Male or female subject age ≥18 years must have a confirmed diagnosis of FSGS defined as a minimum of 1 glomerulus demonstrating segmental sclerosis on light microscopy within the past 5 years.
- Estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, with repeat measurements permitted, as appropriate.
- If eGFR is 30-45 ml/min/1.73 m2, a recent biopsy (within 12 months prior to Screening) must demonstrate <50% tubulo-interstitial fibrosis. The Investigator and the subject may decide to perform a biopsy which might fulfill this eligibility criterion.
- UPCR >1.5 g protein/g creatinine at Screening.
- Based on all previous treatment received for FSGS, subject is eligible if:
a. Subject has been treated with at least 1, and up to 3 classes of Immunosuppressants* either alone or in combination;
b. Subject has a contraindication to any class of Immunosuppressant (may include steroids) or is considered to be intolerant to any class of Immunosuppressant (may include steroids) per Investigator judgment.
- For inclusion into the Lead-in Period, subjects on ongoing corticosteroid treatment must have discontinued steroid treatment or tapered down to a stable prednisone dose ≤7.5 mg per day (or 15 mg q.o.d.) or other steroid equivalent at least one week prior to the Lead-in Period. Treatment with CNIs OR MMF (but not both) may be continued upon entry into the Lead-in Period at the discretion of the Principal Investigator. Treatment with the agent (CNIs or MMF) must have been ongoing for at least 6 months prior to Lead-in, and the dose (or level) of the agent must have been stable for at least 1 month prior to the Lead-in Period.
- Female subjects of non-childbearing potential will meet at least 1 of the following criteria (all other female subjects, including female subjects with tubal ligations, are considered to be of childbearing potential):
a. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with/and have a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure.
|Principal exclusion criteria
|1. Diagnosis of collapsing FSGS.
2. Advanced chronic changes on renal biopsy as evidenced by >50% tubulo-interstitial fibrosis.
3. Evidence or history of clinically significant hematological, endocrine (including Type 1 diabetes mellitus), pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or hepatic disease, like cirrhosis or chronic active liver disease.
4. Organ transplantation.
5. History of any malignancy except for subjects who had a basal or squamous cell skin cancer which has been treated and fully resolved for a minimum of 5 years.
7. Treatment with rituximab within 6 months prior to start of the Lead-in Period. If Rituximab treatment is longer than 6 months (prior to start of the Lead-in Period), subject is still excluded if no peripheral CD19+ B-cells are identified in the local laboratory prior to first study drug dosing.
8.- Any immunosuppressant medication (besides corticosteroids, MMF, or CNIs) within the past 28 days prior to start of the Lead-in Period.
20. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this
21. Subjects with a history of hypersensitivity to the components of the study drug (For Japan, EU member states which participate in the VHP Process, and any additional countries selected for study participation in the future).
|E.5 End points
|Primary end point(s)
|Percentage change from baseline to Week 13 in Urinary Protein to Creatinine Ratio (UPCR).
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|- Adverse Events, Laboratory Safety Tests (Hematology, Clinical Chemistry, Urinalysis), Body Weight, Blood Pressure, Pulse Rate, oral temperature and Electrocardiogram (ECG).
- Percentage change from baseline to Weeks 3, 5 and 9 in UPCR.
- Partial and complete remission of proteinuria at Week 13.
- Percentage change from baseline to Weeks 3, 5, 9 and 13 in estimated glomerular filtration rate (eGFR).
- Serum concentration of PF-06730512.
- Incidence of the development of anti-drug antibody (ADA) and neutralizing antibody (NAb).
|Timepoint(s) of evaluation of this end point
|Weeks 3, 5, 9 and 13 (see above)
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
|Other trial design description
| Comparator of controlled trial
|Other medicinal product(s)
|Same compound, different dose
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days