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Clinical Trial Results:
A Phase 2, 24-Week, Adaptive, Open Label, Sequential Cohort Trial To Evaluate The Efficacy, Safety, Tolerability and Pharmacokinetics of PF-06730512 Following Multiple Doses in Adult Subjects With Focal Segmental Glomerulosclerosis (FSGS)

Summary
EudraCT number	2019-003607-35
Trial protocol	DE SK PL CZ IT
Global end of trial date	14 Feb 2023

Results information
Results version number	v1(current)
This version publication date	17 Feb 2024
First version publication date	17 Feb 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

C0221002

ISRCTN number

US NCT number

NCT03448692

WHO universal trial number (UTN)

Other trial identifiers

ROBO2/PODO: C0221002

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Centre, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Centre, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

25 Sep 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Feb 2023

Was the trial ended prematurely?

Yes

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 subjects with FSGS.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

15 Oct 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 4

Country: Number of subjects enrolled

Czechia: 2

Country: Number of subjects enrolled

Germany: 2

Country: Number of subjects enrolled

Italy: 1

Country: Number of subjects enrolled

Japan: 5

Country: Number of subjects enrolled

Mexico: 1

Country: Number of subjects enrolled

Poland: 4

Country: Number of subjects enrolled

Slovakia: 5

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

United States: 18

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 47 subjects were enrolled into the study. All subjects received treatment.

Period 1 title

Disposition Phase:Screening:up to 43Days

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

PF-06730512 1000 mg IV

Arm description

Subjects received PF-06730512 1000 milligram (mg) intravenously (IV) every 2 weeks (Q2W).

Arm type

Experimental

Investigational medicinal product name

PF-06730512

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received PF-06730512 1000 mg IV Q2W.

PF-06730512 300 mg IV

Arm description

Subjects received PF-06730512 300 mg IV Q2W.

Arm type

Experimental

Investigational medicinal product name

PF-06730512

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received PF-06730512 300 mg IV Q2W.

Number of subjects in period 1	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Started	23	24
Completed	23	24

Period 2 title

Lead in Period:8 Weeks (W)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

PF-06730512 1000 mg IV

Arm description

Subjects received PF-06730512 1000 milligram (mg) intravenously (IV) every 2 weeks (Q2W).

Arm type

Experimental

Investigational medicinal product name

PF-06730512

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received PF-06730512 1000 mg IV Q2W.

PF-06730512 300 mg IV

Arm description

Subjects received PF-06730512 300 mg IV Q2W.

Arm type

Experimental

Investigational medicinal product name

PF-06730512

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received PF-06730512 300 mg IV Q2W.

Number of subjects in period 2	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Started	23	24
Completed	23	24

Period 3 title

Investigational Treatment Period:Upto24W

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

PF-06730512 1000 mg IV

Arm description

Subjects received PF-06730512 1000 milligram (mg) intravenously (IV) every 2 weeks (Q2W).

Arm type

Experimental

Investigational medicinal product name

PF-06730512

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received PF-06730512 1000 mg IV Q2W.

PF-06730512 300 mg IV

Arm description

Subjects received PF-06730512 300 mg IV Q2W.

Arm type

Experimental

Investigational medicinal product name

PF-06730512

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received PF-06730512 300 mg IV Q2W.

Number of subjects in period 3	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Started	23	24
Completed	22	15
Not completed	1	9
Consent withdrawn by subject	-	2
Adverse event, non-fatal	1	-
Study terminated by sponsor	-	5
Lack of efficacy	-	1
Physician's decision	-	1

Period 4 title

Follow up Period: 9 Weeks

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

PF-06730512 1000 mg IV

Arm description

Subjects received PF-06730512 1000 milligram (mg) intravenously (IV) every 2 weeks (Q2W).

Arm type

Experimental

Investigational medicinal product name

PF-06730512

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received PF-06730512 1000 mg IV Q2W.

PF-06730512 300 mg IV

Arm description

Subjects received PF-06730512 300 mg IV Q2W.

Arm type

Experimental

Investigational medicinal product name

PF-06730512

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Subjects received PF-06730512 300 mg IV Q2W.

Number of subjects in period 4	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Started	22	15
Completed	23	23
Joined	1	8
Continued follow-up	1	8

Baseline characteristics

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Reporting group title

Disposition Phase:Screening:up to 43Days

Reporting group description

Reporting group values	Disposition Phase:Screening:up to 43Days	Total
Number of subjects	47	47
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	45	45
From 65-84 years	2	2
85 years and over	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	41.8 ± 14.01	-
Sex: Female, Male
Units: Subjects
Female	22	22
Male	25	25
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	1	1
Asian	8	8
Native Hawaiian or Other Pacific Islander	0	0
Black or African American	2	2
White	36	36
More than one race	0	0
Unknown or Not Reported	0	0
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	8	8
Not Hispanic or Latino	39	39
Unknown or Not Reported	0	0

End points

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Reporting group title

PF-06730512 1000 mg IV

Reporting group description

Subjects received PF-06730512 1000 milligram (mg) intravenously (IV) every 2 weeks (Q2W).

Reporting group title

PF-06730512 300 mg IV

Reporting group description

Subjects received PF-06730512 300 mg IV Q2W.

Reporting group title

PF-06730512 1000 mg IV

Reporting group description

Subjects received PF-06730512 1000 milligram (mg) intravenously (IV) every 2 weeks (Q2W).

Reporting group title

PF-06730512 300 mg IV

Reporting group description

Subjects received PF-06730512 300 mg IV Q2W.

Reporting group title

PF-06730512 1000 mg IV

Reporting group description

Subjects received PF-06730512 1000 milligram (mg) intravenously (IV) every 2 weeks (Q2W).

Reporting group title

PF-06730512 300 mg IV

Reporting group description

Subjects received PF-06730512 300 mg IV Q2W.

Reporting group title

PF-06730512 1000 mg IV

Reporting group description

Subjects received PF-06730512 1000 milligram (mg) intravenously (IV) every 2 weeks (Q2W).

Reporting group title

PF-06730512 300 mg IV

Reporting group description

Subjects received PF-06730512 300 mg IV Q2W.

Primary: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13

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End point title

Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13 ^[1]

End point description

UPCR is a ratio between two measured substances in urine: milligram of protein per millimole (mmol) of creatinine, reported in units mg/mmol. A decrease in UPCR may be associated with improved renal and cardiovascular function. The Full Analysis Set (FAS) was defined as all enrolled subjects who had received at least one dose of study treatment and had at least one post-baseline measurement of UPCR based on 24-hour urine collection. Here, "Number of Subjects Analysed" signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Baseline, Week 13

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	21	19
Units: Percentage change
least squares mean (confidence interval 90%)	-12.283 (-26.096 to 4.112)	-0.045 (-9.528 to 10.432)

No statistical analyses for this end point

Secondary: Number of Subjects With Abnormalities in Laboratory Test Parameters

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End point title

Number of Subjects With Abnormalities in Laboratory Test Parameters

End point description

Hemoglobin(Hg),hematocrit,erythrocytes:<0.8*lower limits of normal(LLN);platelets:<0.5*LLN>1.75*upper LN leukocytes(leu),glucose-fasting:<0.6*LLN>1.5*ULN;lymphocytes(lym),lym/leu, neutrophils(neu),neu/leu,protein,albumin,phosphate,free thyroxine,thyroid stimulating hormone: <0.8*LLN>1.2*ULN;basophils(bas),bas/leu,eosinophils(eos),eos/leu,monocytes(mon),mon/leu:>1.2*ULN;bilirubin (total, direct, indirect):>1.5*ULN;aspartate aminotransferase(AT),alanine AT,lactate dehydrogenase,alkaline phosphatase:>3.0*ULN;blood urea nitrogen,creatinine,cholesterol(total,LDL,HDL),triglycerides,Hg A1C: >1.3*ULN;sodium:<0.95*LLN>1.05*ULN;potassium,chloride,calcium,magnesium,bicarbonate:<0.9*LLN>1.1*ULN;prolactin:>1.1*ULN;creatine kinase:>2.0*ULN;urobilinogen:>=1;Urine-specific gravity:<1.003>1.030,pH:<4.5 >8, glucose,protein,bilirubin,nitrite,leukocyte esterase, ketones:>=1.Categories with at-least 1 non-zero values are reported. SAS population analysed. n= subjects evaluable for specific rows.

End point type

Secondary

End point timeframe

From Day 1 of treatment up to Week 33

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Subjects
Hg<0.8*LLN (n=23,24)	5	4
Hematocrit<0.8*LLN (n=23,24)	5	7
Erythrocytes<0.8*LLN (n=23,24)	3	4
Ery. Mean Corpuscular Volume < 0.9*LLN (n=23,24)	1	0
Ery. Mean Corpuscular Hg<0.9*LLN (n=23,24)	1	0
Platelets>1.75*ULN (n=23,24)	1	0
Lym<0.8*LLN (n=23,24)	0	4
Lym/Leu<0.8*LLN (n=23,24)	1	6
Lym/Leu>1.2*ULN (n=23,24)	0	1
Neu <0.8*LLN (n=23,24)	1	2
Neu >1.2*ULN (n=23,24)	3	4
Neu/Leu<0.8*LLN (n=23,24)	1	1
Neu/Leu>1.2*ULN (n=23,24)	0	1
Eos>1.2*ULN (n=23,24)	2	1
Eos/Leu>1.2*ULN (n=23,24)	3	3
Mon/Leu>1.2*ULN (n=23,24)	0	1
Aspartate AT>3.0*ULN (n=23,23)	1	0
Alanine AT>3.0*ULN (n=23,23)	1	0
Protein<0.8*LLN (n=23,23)	9	11
Albumin<0.8*LLN (n=23,23)	8	11
Blood Urea Nitrogen>1.3*ULN (n=23,23)	10	8
Creatinine>1.3*ULN (n=23,23)	8	12
Urate>1.2*ULN (n=23,23)	3	2
Cholesterol >1.3*ULN (n=23,23)	6	7
HDL Cholesterol<0.8 *LLN (n=23,2)	1	0
LDL Cholesterol>1.2*ULN (n=23,22)	6	5
Triglycerides>1.3*ULN (n=23,23)	6	8
Sodium<0.95*LLN (n=23,23)	1	0
Potassium<0.9*LLN (n=23,23)	1	0
Potassium>1.1*ULN (n=23,23)	1	0
Calcium<0.9*LLN (n=23,23)	1	3
Bicarbonate<0.9*LLN (n=23,23)	0	1
Glucose>1.5*ULN (n=23,23)	2	2
Specific Gravity>1.030 (n=21,24)	5	6
pH>8 (n=23,24)	1	0
Urine Glucose>=1 (n=23,24)	5	10
Urine Protein>=1 (n=23,24)	22	24
Urine Hemoglobin>=1 (n=23,24)	15	17
Nitrite>=1 (n=23,24)	1	3
Leukocyte Esterase>=1 (n=23,24)	5	6
Urine Erythrocytes>=20 (n=22,24)	3	3
Urine Leukocytes>=20 (n=22,24)	2	5
Granular Casts>1 (n=5,2)	4	2
Hyaline Casts>1 (n=18,18)	17	15
Urine Creatinine<40(n=23,24)	9	8
Urine Creatinine>300 (n=23,24)	1	0
Urine (24HR) Creatinine>1.1*ULN (n=23,24)	2	6

No statistical analyses for this end point

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs)

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End point title

Number of Subjects With Treatment Emergent Adverse Events (TEAEs)

End point description

An adverse event was considered treatment emergent relative to a given treatment if the event occurred for the first time during the investigational treatment period and was not seen prior to the start of treatment (during the lead-in period), or the event was seen prior to the start of treatment but increased in severity during treatment. Adverse events occurring during the lead-in period were considered non-treatment emergent. Events that occurred during the follow-up period were counted as treatment emergent and attributed to the previous treatment taken. SAS was defined as all enrolled subjects who had received at least one dose of study treatment.

End point type

Secondary

End point timeframe

From Day 1 of treatment up to 9 weeks after last dose of study treatment (up to Week 33)

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Subjects	20	17

No statistical analyses for this end point

Secondary: Change From Baseline in Body Weight

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End point title

Change From Baseline in Body Weight

End point description

Change from baseline in body weight and at baseline values were reported for this endpoint. SAS was defined as all enrolled subjects who had received at least one dose of study treatment. Here, ‘Number Analysed’ (n) signifies number of subjects evaluable for the specific timepoints.

End point type

Secondary

End point timeframe

Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Kilogram
arithmetic mean (standard deviation)
Baseline (n=23,24)	78.3 ± 17.8	88.9 ± 23.5
Week 2 (n=23,24)	1.0 ± 2.2	-0.3 ± 1.9
Week 3 (n=23,23)	0.4 ± 2.5	-0.3 ± 2.2
Week 5 (n=22,23)	0.5 ± 3.0	-0.5 ± 4.8
Week 7 (n=23,22)	0.6 ± 2.6	-1.0 ± 5.3
Week 9 (n=22,22)	0.1 ± 3.1	-0.4 ± 3.4
Week 11 (n=22,20)	0.7 ± 2.8	-0.1 ± 4.2
Week 13 (n=23,22)	-0.2 ± 1.9	-1.0 ± 3.4
Week15 (n=4,13)	-0.3 ± 1.0	-0.7 ± 4.0
Week 17 (n=4,9)	-0.2 ± 1.2	-1.2 ± 4.8
Week 19 (n=4,9)	-0.4 ± 1.0	-1.3 ± 4.8
Week 21 (n=4,9)	0.3 ± 1.7	-1.3 ± 4.9
Week 23 (n=4,9)	0.3 ± 1.2	-1.5 ± 5.3
Week 25 (n=4,16)	-0.1 ± 1.6	-1.1 ± 4.8
Week 27 (n=4,16)	0.7 ± 1.4	-0.6 ± 5.2
Week 29 (n=4,16)	0.5 ± 1.5	-1.0 ± 4.5
Week 33 (n=4,16)	0.5 ± 1.6	-0.6 ± 5.4

No statistical analyses for this end point

Secondary: Change From Baseline in Blood Pressure

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End point title

Change From Baseline in Blood Pressure

End point description

Change from baseline in blood pressure and at baseline values were reported for this endpoint. SAS was defined as all enrolled subjects who had received at least one dose of study treatment. Here, ‘Number Analysed’ signifies number of subjects evaluable for the specific timepoints.

End point type

Secondary

End point timeframe

Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Millimetre of mercury (mmHg)
arithmetic mean (standard deviation)
Baseline (n=23,24)	131.2 ± 12.8	125.3 ± 11.8
Week 2 (n=23,24)	-1.8 ± 13.1	-1.3 ± 7.8
Week 3 (n=23,23)	-1.3 ± 10.2	1.7 ± 7.5
Week 5 (n=22,23)	-3.0 ± 10.6	-1.9 ± 9.0
Week 7 (n=23,22)	-2.0 ± 11.3	-1.2 ± 9.0
Week 9 (n=22,22)	-5.1 ± 10.7	-2.6 ± 7.6
Week 11 (n=22,20)	-1.5 ± 12.5	-1.6 ± 6.1
Week 13 (n=23,22)	-2.0 ± 11.3	-1.0 ± 10.0
Week15 (n=4,13)	-7.5 ± 5.1	-2.3 ± 6.2
Week 17 (n=4,9)	-7.3 ± 12.7	-7.7 ± 12.2
Week 19 (n=4,9)	-8.0 ± 8.4	0.4 ± 10.7
Week 21 (n=4,9)	-8.0 ± 16.4	-5.8 ± 10.1
Week 23 (n=4,9)	1.0 ± 9.0	-3.6 ± 8.2
Week 25 (n=4,16)	-9.0 ± 13.2	-2.6 ± 11.2
Week 27 (n=4,16)	-3.0 ± 10.4	3.5 ± 10.5
Week 29 (n=4,16)	-8.3 ± 8.4	0.4 ± 11.2
Week 33 (n=4,16)	-12.0 ± 20.7	4.6 ± 8.9

No statistical analyses for this end point

Secondary: Change From Baseline in Pulse Rate

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End point title

Change From Baseline in Pulse Rate

End point description

Change from baseline in pulse rate and at baseline values were reported for this endpoint. SAS was defined as all enrolled subjects who had received at least one dose of study treatment. Here, ‘Number Analysed’ signifies number of subjects evaluable for the specific timepoints.

End point type

Secondary

End point timeframe

Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Beats per minute
arithmetic mean (standard deviation)
Baseline (n=23,24)	74.1 ± 11.8	74.2 ± 11.0
Week 2 (n=23,24)	2.1 ± 9.6	0.6 ± 6.9
Week 3 (n=23,23)	-0.6 ± 8.0	-1.1 ± 6.0
Week 5 (n=22,23)	0.0 ± 7.3	-0.3 ± 8.0
Week 7 (n=23,22)	-0.3 ± 9.2	0.0 ± 7.9
Week 9 (n=22,22)	-1.0 ± 11.1	1.5 ± 9.0
Week 11 (n=22,20)	-1.7 ± 10.8	0.6 ± 6.6
Week 13 (n=23,22)	3.3 ± 11.9	0.5 ± 6.9
Week 15 (n=4,13)	-5.8 ± 10.4	5.0 ± 10.1
Week 17 (n=4,9)	-6.3 ± 8.8	-2.2 ± 5.0
Week 19 (n=4,9)	-3.5 ± 13.7	2.9 ± 6.5
Week 21 (n=4,9)	-5.5 ± 12.8	-1.6 ± 5.0
Week 23 (n=4,9)	-3.3 ± 10.5	-3.1 ± 9.0
Week 25 (n=4,16)	-6.3 ± 12.5	1.8 ± 7.6
Week 27 (n=4,16)	-0.8 ± 16.0	2.9 ± 7.2
Week 29 (n=4,16)	2.5 ± 14.8	5.9 ± 8.8
Week 33 (n=4,16)	-0.5 ± 15.3	6.2 ± 10.0

No statistical analyses for this end point

Secondary: Change From Baseline in Body Temperature

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End point title

Change From Baseline in Body Temperature

End point description

Change from baseline in body temperature and at baseline values were reported for this endpoint. SAS was defined as all enrolled subjects who had received at least one dose of study treatment. Here, ‘Number Analysed’ signifies number of subjects evaluable for the specific timepoints.

End point type

Secondary

End point timeframe

Baseline, Change at Weeks 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Degree Celsius
arithmetic mean (standard deviation)
Baseline (n=23,24)	36.4 ± 0.4	36.6 ± 0.2
Week 2 (n=23,24)	0.1 ± 0.4	-0.0 ± 0.3
Week 3 (n=23,23)	0.0 ± 0.2	-0.1 ± 0.3
Week 5 (n=22,23)	0.0 ± 0.4	-0.1 ± 0.3
Week 7 (n=23,22)	0.1 ± 0.3	-0.0 ± 0.3
Week 9 (n=22,22)	0.0 ± 0.4	-0.1 ± 0.3
Week 11 (n=22,20)	0.1 ± 0.3	-0.0 ± 0.3
Week 13 (n=23,22)	-0.1 ± 0.4	-0.0 ± 0.2
Week 15 (n=4,13)	0.2 ± 0.2	0.1 ± 0.2
Week 17 (n=4,9)	0.1 ± 0.2	0.1 ± 0.2
Week 19 (n=4,9)	0.1 ± 0.4	0.1 ± 0.3
Week 21 (n=4,9)	-0.0 ± 0.1	-0.1 ± 0.5
Week 23 (n=4,9)	0.2 ± 0.2	0.0 ± 0.3
Week 25 (n=4,16)	0.1 ± 0.2	0.0 ± 0.2
Week 27 (n=4,16)	0.1 ± 0.1	0.1 ± 0.2
Week 29 (n=4,16)	0.1 ± 0.3	-0.1 ± 0.4
Week 33 (n=4,16)	0.1 ± 0.1	-0.1 ± 0.3

No statistical analyses for this end point

Secondary: Number of Subjects With Abnormalities in Electrocardiogram (ECG)

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End point title

Number of Subjects With Abnormalities in Electrocardiogram (ECG)

End point description

ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): greater than (>) 450, >480, >500, increase from baseline >30, increase from baseline >60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 3) Heart rate (bpm): RR decrease >25% and to a VR (interval between QRS wave and T wave on ECG) >100; RR (interval between 2 successive R waves on ECG) increase >25% and to a VR <50; 4) Pulse rate (msec): increase >25% and to a value >200; 5) QT (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 6) QRS (msec): increase >25% and to a value >110. Categories (timepoints) with at least 1 subject having ECG abnormality in any of the reporting arms, were reported for this endpoint. SAS population was analyzed. N= subjects evaluable for this endpoint. n= subjects evaluable for specific timepoints.

End point type

Secondary

End point timeframe

Weeks 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 33

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	23
Units: Subjects
Week 3 (Not Clinically Significant) (n=23,23)	3	4
Week 3 (Clinically Significant) (n=23,23)	1	0
Week 7 (Not Clinically Significant) (n=22,22)	3	4
Week 7 (Clinically Significant) (n=22,22)	0	0
Week 11 (Not Clinically Significant) (n=22,20)	4	4
Week 11 (Clinically Significant) (n=22,20)	1	0
Week 13 (Not Clinically Significant) (n=23,22)	6	4
Week 13 (Clinically Significant) (n=23,22)	1	0
Week 17 (Not Clinically Significant) (n=4,9)	0	0
Week 17 (Clinically Significant) (n=4,9)	0	0
Week 21 (Not Clinically Significant) (n=4,9)	1	1
Week 21 (Clinically Significant) (n=4,9)	0	0
Week 25 (Not Clinically Significant) (n=4,16)	1	1
Week 25 (Clinically Significant) (n=4,16)	0	0
Week 33 (Not Clinically Significant) (n=3,16)	0	2
Week 33 (Clinically Significant) (n=3,16)	0	0

No statistical analyses for this end point

Secondary: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 2, 5, 9 and 13

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End point title

Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 2, 5, 9 and 13

End point description

UPCR is a ratio between two measured substances in urine: mmol of creatinine, reported in units mg/mmol. A decrease in UPCR may be associated with improved renal and cardiovascular function. FAS was defined as all enrolled subjects who had received at least one dose of study treatment and had at least one post-baseline measurement of UPCR based on 24-hour urine collected. Here, ‘Number Analysed’ signifies number of subjects evaluable for the specific timepoints.

End point type

Secondary

End point timeframe

Baseline, Weeks 2, 5, 9 and 13

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Percent change
least squares mean (confidence interval 90%)
Week 2 (n=0,0)	0 (0 to 0)	0 (0 to 0)
Week 5 (n=20,20)	6.250 (-7.035 to 21.433)	-3.788 (-11.344 to 4.411)
Week 9 (n=19,20)	-11.335 (-20.746 to -0.807)	-2.354 (-11.069 to 7.215)
Week 13 (n=21,19)	-12.283 (-26.096 to 4.112)	-0.045 (-9.528 to 10.432)

No statistical analyses for this end point

Secondary: Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR ) at Weeks 3, 5, 9 and 13

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End point title

Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR ) at Weeks 3, 5, 9 and 13

End point description

The eGFR was calculated using 4 variable formula developed by the modification of diet in renal disease (MDRD) study group. The 4 variables needed to estimate glomerular filtration rate (GFR) using this formula were serum creatinine concentration, age, sex (for females, eGFR was multiplied by 0.742) and ethnic origin (for African-Caribbean people only, eGFR was multiplied by 1.212). Thus eGFR in milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) = 175*(sCr/88.4)^-1.154*(Age)^-0.203*(0.742 if female)*(1.212 if African-Caribbean). Baseline eGFR was determined predose at Week 0 (Day 1). For Baseline eGFR, the “Low eGFR” group was defined as baseline eGFR < 45 mL/min/1.73m2, and the “High eGFR” group was defined as baseline eGFR > 45 mL/min/1.73 m2. FAS was defined as all enrolled subjects who had received at least one dose of study treatment and had at least one post-baseline measurement of UPCR based on 24-hour urine collected. n= subjects evaluable for specific timepoints.

End point type

Secondary

End point timeframe

Baseline, Weeks 3, 5, 9 and 13

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Percent change
least squares mean (confidence interval 90%)
Week 3 (n=23,22)	5.657 (-0.722 to 12.446)	-0.180 (-4.179 to 3.987)
Week 5 (n=21,23)	2.174 (-3.012 to 7.637)	-2.038 (-8.008 to 4.319)
Week 9 (n=22,22)	-1.536 (-15.575 to 14.838)	-5.017 (-11.596 to 2.052)
Week 13 (n=23,22)	2.892 (-6.096 to 12.740)	-12.217 (-18.831 to -5.063)

No statistical analyses for this end point

Secondary: Serum PF-06730512 Concentration Versus Time Summary

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End point title

Serum PF-06730512 Concentration Versus Time Summary

End point description

The PK concentration analysis set was defined as all enrolled subjects treated who received at least one dose of PF-06730512 and had at least 1 measurable concentration. Here, ‘Number Analyzed’ signifies number of subjects evaluable for the specific rows. Here, ‘99999’ indicates data could not be estimated as only one subject was evaluated.

End point type

Secondary

End point timeframe

30 minutes pre-dose on Day 1, 8, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155, 169, follow-up (Fup) visit on Day 99, 113, 141, 183, 197, 225 and 1 hour post-dose on Day 1, 71, 155

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Microgram per millilitre
arithmetic mean (standard deviation)
Day 1 (n=17,22)	279.4 ± 86.548	71.94 ± 29.668
Day 8 (n=1,10)	39.50 ± 99999	13.09 ± 6.9363
Day 15 (n=23,21)	16.45 ± 11.266	5.096 ± 3.1184
Day 29 (n=21,19)	24.92 ± 20.256	6.916 ± 5.0154
Day 43 (n=20,19)	29.96 ± 22.062	6.991 ± 5.5862
Day 57 (n=21,18)	32.56 ± 23.031	7.664 ± 6.1325
Day 71 (n=17,17)	27.32 ± 16.688	6.736 ± 5.6237
Day 85 (n=4,13)	41.15 ± 23.516	7.597 ± 6.9184
Day 99/Fup (n=19,7)	11.50 ± 12.948	2.313 ± 3.1827
Day 113/Fup (n=19,7)	4.991 ± 6.1121	0.6356 ± 0.81118
Day 141/Fup (n=18,7)	1.385 ± 2.1196	0.1438 ± 0.21666
Day 99 (n=4,9)	35.65 ± 16.065	7.084 ± 6.9224
Day 113 (n=4,6)	42.40 ± 25.049	9.442 ± 8.6965
Day 127 (n=3,6)	30.67 ± 5.3463	6.732 ± 5.2295
Day 141 (n=4,7)	38.00 ± 13.880	8.957 ± 10.753
Day 155 (n=3,8)	32.57 ± 5.8287	7.585 ± 8.1601
Day 169 (n=4,16)	29.32 ± 15.338	7.989 ± 7.4740
Day 183/Fup (n=4,16)	25.79 ± 30.417	3.046 ± 3.8895
Day 197/Fup (n=4,16)	6.108 ± 4.0049	1.048 ± 1.4978
Day 225/Fup (n=4,16)	2.009 ± 1.6808	0.2659 ± 0.45714

No statistical analyses for this end point

Secondary: Number of Subjects With Positive Anti-Drug Antibody (ADA) and/or Neutralizing Antibody(NAb)

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End point title

Number of Subjects With Positive Anti-Drug Antibody (ADA) and/or Neutralizing Antibody(NAb)

End point description

The immunogenicity analysis population included all treated subjects with at least 1 ADA sample (pre-dose or post-treatment) analysed. Subjects those had only pre-dose baseline data and no post-treatment immunogenicity data, was not evaluated for subject-level ADA. Here, ‘Number Analyzed’ signifies number of subjects evaluable for the specific rows.

End point type

Secondary

End point timeframe

From Day 1 of treatment up to Week 33

End point values	PF-06730512 1000 mg IV	PF-06730512 300 mg IV
Number of subjects analysed	23	24
Units: Subjects
ADA Positive (n=21,24)	1	0
NAb Positive (n=21,24)	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Day 1 of treatment up to 9 weeks after last dose of study treatment (up to Week 33)

Adverse event reporting additional description

Same event may appear as both non-SAE and a serious AE. However, what is presented are distinct events. An event may be categorised as serious in one subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

PF-06730512 300 mg IV

Reporting group description

Subjects received PF-06730512 300 mg IV Q2W.

Reporting group title

PF-06730512 1000 mg IV

Reporting group description

Subjects received PF-06730512 1000 mg IV Q2W.

Serious adverse events	PF-06730512 300 mg IV	PF-06730512 1000 mg IV
Total subjects affected by serious adverse events
subjects affected / exposed	2 / 24 (8.33%)	2 / 23 (8.70%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
General disorders and administration site conditions
Disease progression
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Renal impairment
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
COVID-19
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypervolaemia
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	PF-06730512 300 mg IV	PF-06730512 1000 mg IV
Total subjects affected by non serious adverse events
subjects affected / exposed	12 / 24 (50.00%)	11 / 23 (47.83%)
Investigations
SARS-CoV-2 test positive
subjects affected / exposed	2 / 24 (8.33%)	2 / 23 (8.70%)
occurrences all number	2	2
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)
occurrences all number	2	0
Nervous system disorders
Headache
subjects affected / exposed	3 / 24 (12.50%)	2 / 23 (8.70%)
occurrences all number	3	3
Dizziness
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)
occurrences all number	3	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 24 (0.00%)	2 / 23 (8.70%)
occurrences all number	0	2
Oedema
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)
occurrences all number	2	0
Fatigue
subjects affected / exposed	2 / 24 (8.33%)	3 / 23 (13.04%)
occurrences all number	2	4
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	2 / 24 (8.33%)	1 / 23 (4.35%)
occurrences all number	3	1
Vomiting
subjects affected / exposed	1 / 24 (4.17%)	2 / 23 (8.70%)
occurrences all number	2	2
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 24 (0.00%)	2 / 23 (8.70%)
occurrences all number	0	2
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 24 (0.00%)	2 / 23 (8.70%)
occurrences all number	0	2
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)
occurrences all number	2	0
Flank pain
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)
occurrences all number	2	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)
occurrences all number	3	0
Nasopharyngitis
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)
occurrences all number	2	0
COVID-19
subjects affected / exposed	2 / 24 (8.33%)	1 / 23 (4.35%)
occurrences all number	2	1
Viral infection
subjects affected / exposed	0 / 24 (0.00%)	2 / 23 (8.70%)
occurrences all number	0	2
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 24 (0.00%)	2 / 23 (8.70%)
occurrences all number	0	2

More information

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Were there any global substantial amendments to the protocol? Yes

09 May 2018

Specifications for dose levels, dosing frequency and route of administration have been included. Randomisation of subjects to the high versus the low dose has been removed. Instead, a sequential design has been implemented allowing Cohort 1 enrollment to complete prior to enrolment of Cohort 2.

10 Jun 2019

Changes in Inclusion and Exclusion Criteria and addition of the optional renal biopsy sub-study.

03 Jan 2020

Changes to Inclusion/Exclusion criteria.

12 Jun 2020

Revision/Clarification to contraception language for EU member states and Japan.

18 Aug 2021

The purpose of this amendment was to extend treatment duration from 12 weeks to 24 weeks, and to add an optional cohort to potentially explore a higher dose.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 2, 24-Week, Adaptive, Open Label, Sequential Cohort Trial To Evaluate The Efficacy, Safety, Tolerability and Pharmacokinetics of PF-06730512 Following Multiple Doses in Adult Subjects With Focal Segmental Glomerulosclerosis (FSGS)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13

Primary: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) Based on 24-hour Urine Collection at Week 13

Secondary: Number of Subjects With Abnormalities in Laboratory Test Parameters

Secondary: Number of Subjects With Abnormalities in Laboratory Test Parameters

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs)

Secondary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs)

Secondary: Change From Baseline in Body Weight

Secondary: Change From Baseline in Body Weight

Secondary: Change From Baseline in Blood Pressure

Secondary: Change From Baseline in Blood Pressure

Secondary: Change From Baseline in Pulse Rate

Secondary: Change From Baseline in Pulse Rate

Secondary: Change From Baseline in Body Temperature

Secondary: Change From Baseline in Body Temperature

Secondary: Number of Subjects With Abnormalities in Electrocardiogram (ECG)

Secondary: Number of Subjects With Abnormalities in Electrocardiogram (ECG)

Secondary: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 2, 5, 9 and 13

Secondary: Percentage Change From Baseline in Urinary Protein to Creatinine Ratio (UPCR) at Weeks 2, 5, 9 and 13

Secondary: Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR ) at Weeks 3, 5, 9 and 13

Secondary: Percentage Change From Baseline in Estimated Glomerular Filtration Rate (eGFR ) at Weeks 3, 5, 9 and 13

Secondary: Serum PF-06730512 Concentration Versus Time Summary

Secondary: Serum PF-06730512 Concentration Versus Time Summary

Secondary: Number of Subjects With Positive Anti-Drug Antibody (ADA) and/or Neutralizing Antibody(NAb)

Secondary: Number of Subjects With Positive Anti-Drug Antibody (ADA) and/or Neutralizing Antibody(NAb)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, 24-Week, Adaptive, Open Label, Sequential Cohort Trial To Evaluate The Efficacy, Safety, Tolerability and Pharmacokinetics of PF-06730512 Following Multiple Doses in Adult Subjects With Focal Segmental Glomerulosclerosis (FSGS)