| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Focal Segmental Glomerulosclerosis (FSGS) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Male diseases of the urinary and reproductive systems [C12] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10067757 |
| E.1.2 | Term | Focal segmental glomerulosclerosis |
| E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
|
| 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 evaluate the efficacy of PF-06730512 compared to baseline in the reduction of proteinuria following 24 weeks of treatment in patients with FSGS. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of PF-06730512 following 24 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. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2- 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.
3- 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.
4- UPCR >1.5 g protein/g creatinine at Screening.
5- 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;
OR
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.
6.Subjects on ongoing corticosteroid treatment must have received an adequate course and be on a stable dose for at least 4 weeks prior to the Lead-in Period and expected to remain stable throughout the study. The same requirements apply to ongoing treatment with CNIs and/or MMF so long as subjects have been receiving either or both of these treatments for at least 3 months prior to the Lead-in Period. Refer to Section 5.8.1 for additional information.
7.Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures including completion of daily diaries to record symptoms and urine collections.
8- 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. |
|
| E.4 | 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.
6.Body mass index (BMI) >45 kg/m2 (based on an estimated dry weight as per judgment of the investigator, if applicable).
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. The following immunosuppressant medications within the past 28 days prior to start of the Lead in Period: azathioprine (Imuran), cytotoxic agents, acthar.
9.Excessive alcohol consumption that may impair the subject's ability to participate in the study per investigator judgment in accordance with national guidelines, if available.
10. Screening sitting blood pressure (BP) ≥155 mm Hg (systolic) or ≥95mm Hg (diastolic), following at least 5 minutes of sitting rest. If BP is ≥ 155 mm Hg (systolic) or ≥95 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the subject's eligibility. Repeat BP measurements on a different day are allowed to meet this eligibility criterion. Note: Repeat BP measurement should be done within designated screening window and may be considered as unplanned visit.
11. Active/serious infection including, but not limited to, Hepatitis B or C, human immunodeficiency virus (HIV). This includes subjects with a known history of cytomegalovirus (CMV), CMV mononucleosis, gammaherpesviral mononucleosis, parvovirus infection, or simian virus 40 infection. Note: Laboratory test results for these types of infections may require medical interpretation by the investigator and consultation with the Sponsor or designee.
12.Subjects with a history of bilateral vesicoureteral reflux.
13.Subjects with a history of prior treatment with or use of interferon, lithium, pamidronate, mTOR inhibitors (eg, sirolimus), testosterone/anabolic steroids, anthracycline (eg, doxorubicin), heroin.
14.Subjects with ANY of the following abnormalities in clinical laboratory tests at Screening, as assessed by the study specific laboratory and confirmed by a repeat test, if deemed necessary:
a.Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level 1.5× upper limit of normal (ULN);
b.Total bilirubin level 1.5× ULN; subjects with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.
15.Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
16.Previous known participation in a study investigating PF 06730512.
17.Participation in other studies involving investigational drug(s) within 30 days (or as determined by the local requirement) or 5 half lives prior to study entry and/or during study participation.
18.A positive urine drug test at Screening (except positive for tetrahydrocannabinol [THC]).
19.Pregnant female subjects; breastfeeding female subjects; lactating female subjects; male subjects and female subjects of childbearing potential who are unwilling or unable to use 1 highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 9 weeks (63 days) after the last dose of investigational product.
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
study.
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 |
| E.5.1 | Primary end point(s) |
| Percentage change from baseline to Week 13 in Urinary Protein to Creatinine Ratio (UPCR). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | 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 2, 5, 9 and beyond Week 13, as applicable, in UPCR.
- 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). |
|
| E.5.2.1 | 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 |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| 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 | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| Same compound, different dose |
|
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 |
| Mexico |
| Thailand |
| Canada |
| Czechia |
| France |
| Germany |
| Italy |
| Japan |
| Poland |
| Slovakia |
| Spain |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 25 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 24 |
Print
