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Clinical Trial Results:
Phase IIa study to evaluate the safety, pharmacokinetics, and pharmacodynamics of repeated administrations over 4 weeks of the hepcidin antagonist PRS-080#022-DP in anemic chronic kidney disease patients undergoing hemodialysis

Summary
EudraCT number	2016-004472-21
Trial protocol	DE CZ
Global end of trial date	20 Mar 2019

Results information
Results version number	v1(current)
This version publication date	06 Mar 2020
First version publication date	06 Mar 2020
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

PCS_03_16

ISRCTN number

US NCT number

NCT03325621

WHO universal trial number (UTN)

Sponsor organisation name

Pieris Pharmaceuticals GmbH

Sponsor organisation address

Lise-Meitner-Straße 30, Freising-Weihenstephan, Germany, 85354

Public contact

Project leader, Pieris Pharmaceuticals GmbH, +1 3479520110, bruns@pieris.com

Scientific contact

Project leader, Pieris Pharmaceuticals GmbH, +1 3479520110, bruns@pieris.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

20 Mar 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

20 Mar 2019

Global end of trial reached?

Yes

Global end of trial date

20 Mar 2019

Was the trial ended prematurely?

Main objective of the trial

The primary objective of the study was to determine the safety and tolerability of five repeated intravenous administrations of PRS-080#022-DP at 4 and 8 mg/kg body weight (BW) in anemic stage 5 CKD patients requiring hemodialysis.

Protection of trial subjects

Safety data were weekly reviewed by a drug safety monitoring board (DSMB) during the study. During the study, three DSMB meetings were performed to review safety, pharmacokinetic (PK) and pharmacodynamic (PD) data to recommend: I) a continuation of patient enrollment in the 4 mg/kg BW cohort after the treatment of sentinel patients; II) a dose escalation to 8 mg/kg BW after all patients in the 4 mg/kg BW cohort completed Day 18; III) a continuation of patient enrollment in the 8 mg/kg BW cohort after the treatment of sentinel patients. At the end of the study, a final evaluation of all safety, PD and PK data was performed by the DSMB.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Oct 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 8

Country: Number of subjects enrolled

Germany: 4

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

Male and post-menopausal female patients with an age of ≥18 years were recruited in two centers in Germany and three centers in the Czech Republic. The first patient signed the informed consent form on 17-Oct-2017 and the last patient on 05-Nov-2018.

Screening details

24 patients were screened. 12 eligible patients were included in two cohorts of six patients. In each cohort, the first two patients were randomized in a 1:1 ratio and the remaining patients in a 3:1 ratio to active (4 mg/kg PRS-080#022-DP in cohort 1 and 8 mg/kg PRS-080#022-DP in cohort 2) or placebo treatment.

Period 1 title

Overall treatment (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

Double-blinding in the study was ensured by identical infusion bags, labeling, and appearance of PRS-080#022-DP and placebo.

Are arms mutually exclusive

Yes

Placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients received five doses of placebo once a week over five weeks by slow intravenous infusion over 60 minutes using an infusion pump.

4 mg/kg BW PRS-080#022-DP

Arm description

Arm type

Experimental

Investigational medicinal product name

PRS-080#022-DP

Investigational medicinal product code

Other name

Anticalin® protein targeting hepcidin

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients received five doses of 4 mg/kg BW PRS-080#022-DP once a week over five weeks by slow intravenous infusion over 60 minutes using an infusion pump.

8 mg/kg BW PRS-080#022-DP

Arm description

Arm type

Experimental

Investigational medicinal product name

PRS-080#022-DP

Investigational medicinal product code

Other name

Anticalin® protein targeting hepcidin

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients received five doses of 8 mg/kg BW PRS-080#022-DP once a week over five weeks by slow intravenous infusion over 60 minutes using an infusion pump.

Number of subjects in period 1	Placebo	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Started	4	4	4
Completed	4	4	3
Not completed	0	0	1
Protocol deviation	-	-	1

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

4 mg/kg BW PRS-080#022-DP

Reporting group description

Reporting group title

8 mg/kg BW PRS-080#022-DP

Reporting group description

Reporting group values	Placebo	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP	Total
Number of subjects	4	4	4	12
Age categorical
Units: Subjects
Adults (≥18 years)	4	4	4	12
Age continuous
Units: years
median (full range (min-max))	67.0 (30 to 79)	60.5 (30 to 71)	51.5 (39 to 70)	-
Gender categorical
Units: Subjects
Female	1	0	2	3
Male	3	4	2	9
Body weight
Units: kilogram(s)
median (full range (min-max))	76.3 (68.7 to 76.5)	72.5 (57.2 to 81.5)	71.0 (55.0 to 87.1)	-
Body mass index
Units: kilogram(s)/square meter
median (full range (min-max))	24.5 (22.4 to 25.2)	22.4 (18.7 to 27.8)	25.7 (19.0 to 29.4)	-

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

4 mg/kg BW PRS-080#022-DP

Reporting group description

Reporting group title

8 mg/kg BW PRS-080#022-DP

Reporting group description

Primary: Safety and tolerability

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End point title

Safety and tolerability ^[1]

End point description

The safety and tolerability of repeated constant dose administrations of PRS-080#022-DP were evaluated by the assessment of adverse events (AEs), laboratory parameters (hematology, biochemistry, coagulation), vital signs, physical examination, and electrocardiogram (ECG) during the treatment period and follow-up.

End point type

Primary

End point timeframe

From first study treatment (Day 0) until the end of the follow-up period (Day 112).

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: No statistical analysis for this endpoint was done.

End point values	Placebo	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Number of subjects analysed	4	4	4
Units: Subject(s)
All treatment-emergent AEs (TEAEs)	4	4	4
Study drug-related TEAEs	0	1	0
Clinical laboratory abnormalities reported as TEAE	1	1	2
Clinically significant (CS) changes in vital signs	0	0	0
CS changes in ECG values	0	0	0
CS changes in physical examination results	0	1	2

No statistical analyses for this end point

Secondary: Pharmacokinetic end point Cmax

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End point title

Pharmacokinetic end point Cmax ^[2]

End point description

The maximum plasma concentration (Cmax) of total and free PRS-080#022-DP were directly obtained from the measured concentrations.

End point type

Secondary

End point timeframe

Blood samples were collected after dialysis immediately before study drug infusion and immediately after infusion end on Days 0, 7, 14, 21 and 28. Additional blood samples were taken before dialysis on Days 2, 9, 16, 18, 23, 30, 35, 42, 49, 56, 84 and 112

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No pharmacokinetics of PRS-080#022-DP was done for placebo treated patients.

End point values	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Number of subjects analysed	4	4
Units: microgram(s)/millilitre
geometric mean (geometric coefficient of variation)
total PRS-080#022-DP	119 ( 24.5 )	317 ( 43.6 )
free PRS-080#022-DP	67.4 ( 51.6 )	170 ( 57.3 )

No statistical analyses for this end point

Secondary: Pharmacokinetic end point Ctrough

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End point title

Pharmacokinetic end point Ctrough ^[3]

End point description

The plasma concentration immediately before the drug infusion (Ctrough) was directly obtained from the measured concentrations.

End point type

Secondary

End point timeframe

Blood samples for Ctrough assessment were collected after dialysis immediately before study drug infusion on Days 7, 14, 21 and 28.

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No pharmacokinetics of PRS-080#022-DP was done for placebo treated patients.

End point values	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Number of subjects analysed	4	4
Units: microgram(s)/millilitre
geometric mean (geometric coefficient of variation)
Day 7 for total PRS-080#022-DP	18.9 ( 17.3 )	45.1 ( 28.2 )
Day 7 for free PRS-080#022-DP	0.815 ( 24.5 )	2.85 ( 22.1 )
Day 14 for total PRS-080#022-DP	30.7 ( 20.5 )	64.7 ( 30.8 )
Day 14 for free PRS-080#022-DP	1.17 ( 32.6 )	3.97 ( 22.9 )
Day 21 for total PRS-080#022-DP	37.3 ( 5.5 )	93.2 ( 24.1 )
Day 21 for free PRS-080#022-DP	2.05 ( 23.3 )	7.37 ( 83.8 )
Day 28 for total PRS-080#022-DP	44.5 ( 9.0 )	114 ( 8.0 )
Day 28 for free PRS-080#022-DP	2.43 ( 7.3 )	5.66 ( 30.3 )

No statistical analyses for this end point

Secondary: Pharmacokinetic end point tmax

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End point title

Pharmacokinetic end point tmax ^[4]

End point description

The time of observed maximum concentration (tmax) for total and free PRS-080#022-DP were directly obtained from the measured plasma concentrations.

End point type

Secondary

End point timeframe

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No pharmacokinetics of PRS-080#022-DP was done for placebo treated patients.

End point values	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Number of subjects analysed	4	4
Units: hour
median (full range (min-max))
total PRS-080#022-DP	504.9 (1.0 to 672.9)	528.7 (337.8 to 672.7)
free PRS-080#022-DP	504.4 (1.0 to 672.9)	528.9 (505.3 to 672.7)

No statistical analyses for this end point

Secondary: Pharmacodynamic end point changes in plasma hepcidin levels from baseline

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End point title

Pharmacodynamic end point changes in plasma hepcidin levels from baseline

End point description

End point type

Secondary

End point timeframe

Blood samples were collected before dialysis as well as immediately and two hours after infusion end on Days 0, 7, 14, 21 and 28. Additional blood samples were taken before dialysis on Days 2, 4, 9, 11, 16, 18, 23, 30, 32, 35, 42, 49 and 56.

End point values	Placebo	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Number of subjects analysed	4 ^[5]	4	3
Units: nanomole(s)
arithmetic mean (full range (min-max))
Day 0 (infusion end)	-10.7 (-20.4 to -0.9)	-13.9 (-25.4 to -8.2)	-11.0 (-13.2 to -7.5)
Day 0 (2 h after infusion end)	-2.8 (-15.6 to 20.2)	-13.7 (-25.4 to -8.2)	-10.6 (-12.5 to -7.1)
Day 2 (before dialysis)	7.6 (-10.1 to 15.3)	59.7 (20.0 to 88.8)	27.9 (-2.0 to 76.0)
Day 7 (before dialysis)	6.6 (-11.8 to 34.0)	30.1 (14.2 to 47.9)	83.4 (57.6 to 103.7)
Day 7 (infusion end)	-6.3 (-21.5 to 14.5)	-11.2 (-23.5 to -6.9)	-5.0 (-9.1 to -2.9)
Day 7 (2 h after infusion end)	-4.0 (-24.7 to 23.1)	-11.9 (-23.3 to -6.5)	-3.1 (-6.7 to -1.1)
Day 9 (before dialysis)	0.1 (-8.4 to 9.0)	64.8 (12.4 to 130.6)	69.4 (11.3 to 165.8)
Day 14 (before dialysis)	-4.8 (-26.1 to 9.3)	38.5 (22.6 to 50.5)	163.3 (135.5 to 201.7)
Day 14 (infusion end)	-5.4 (-19.0 to 6.4)	-11.1 (-23.4 to -6.6)	-4.7 (-8.4 to 0.3)
Day 14 (2 h after infusion end)	0.6 (-12.3 to 15.3)	-11.7 (-23.2 to -6.3)	-0.9 (-3.0 to 1.5)
Day 16 (before dialysis)	-3.5 (-30.5 to 12.6)	71.6 (31.8 to 110.6)	121.2 (33.2 to 183.8)
Day 21 (before dialysis)	-4.3 (-18.9 to 10.3)	51.4 (30.8 to 77.3)	162.0 (119.5 to 219.7)
Day 21 (infusion end)	-9.6 (-25.6 to 3.6)	-10.6 (-23.5 to -3.31)	-3.6 (-9.2 to 2.8)
Day 21 (2 h after infusion end)	-5.6 (-21.4 to 12.6)	-9.7 (-24.0 to -1.2)	9.3 (-8.1 to 26.5)
Day 23 (before dialysis)	0.5 (-27.4 to 16.7)	122.9 (94.8 to 142.2)	79.4 (34.3 to 149.8)
Day 28 (before dialysis)	-7.0 (-28.1 to 2.0)	47.5 (42.5 to 54.0)	193.3 (115.5 to 315.7)
Day 28 (infusion end)	-14.6 (-30.2 to -2.8)	-10.6 (-23.2 to -5.4)	5.4 (-7.4 to 22.2)
Day 28 (2 h after infusion end)	-8.8 (-28.0 to 9.8)	-11.1 (-21.6 to -6.9)	0.4 (-6.5 to 14.0)
Day 30 (before dialysis)	-4.2 (-20.7 to 8.4)	83.0 (43.5 to 103.8)	40.6 (16.3 to 62.0)
Day 35 (before dialysis)	-5.8 (-27.3 to 8.6)	55.0 (36.0 to 100.8)	160.7 (148.8 to 180.7)
Day 42 (before dialysis)	-6.1 (-26.1 to 11.2)	27.2 (19.9 to 40.9)	97.7 (92.7 to 104.8)
Day 49 (before dialysis)	-4.8 (-27.6 to 10.3)	19.0 (3.1 to 48.1)	73.9 (40.5 to 111.8)
Day 56 (before dialysis)	-1.9 (-17.3 to 6.9)	8.1 (-1.6 to 13.2)	31.4 (22.4 to 41.7)

Attachments

Hepcidin plasma levels – Mean change from baseline

Notes
[5] - N=3 on Day 14 (infusion end and 2 h after infusion end) and Day 42

No statistical analyses for this end point

Secondary: Pharmacodynamic end point AUC of serum iron

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End point title

Pharmacodynamic end point AUC of serum iron

End point description

The area under the curve (AUC)0-t (t = Days 7, 28, and 35) was calculated relative to the baseline value using the linear trapezoidal rule.

End point type

Secondary

End point timeframe

Blood samples were collected before dialysis and two hours after infusion end on Days 0, 7, 14, 21 and 28. Additional blood samples were taken before dialysis on Days 2, 4, 9, 11, 16, 18, 23, 30, 32, 35, 42, 49 and 56.

End point values	Placebo	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Number of subjects analysed	4	4	3
Units: h*µmol/L
arithmetic mean (full range (min-max))
AUC0-Day 7	1302 (1152 to 1422)	3677 (2147 to 4703)	4219 (3571 to 5413)
AUC0-Day 28	6866 (6205 to 8537)	14625 (10443 to 17595)	16360 (12328 to 21331)
AUC0-Day 35	8514 (7407 to 10844)	18247 (12342 to 22379)	20519 (16050 to 26446)

No statistical analyses for this end point

Secondary: Pharmacodynamic end point AUC of transferin saturation in serum

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End point title

Pharmacodynamic end point AUC of transferin saturation in serum

End point description

The area under the curve (AUC)0-t (t = Days 7, 28, and 35) was calculated relative to the baseline value using the linear trapezoidal rule.

End point type

Secondary

End point timeframe

End point values	Placebo	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Number of subjects analysed	4	4	3
Units: h*%
arithmetic mean (full range (min-max))
AUC0-Day 7	3242 (2280 to 3695)	6956 (3936 to 8832)	8130 (7461 to 9355)
AUC0-Day 28	16952 (12588 to 23004)	28833 (20412 to 36254)	32495 (27879 to 35865)
AUC0-Day 35	20974 (15842 to 29303)	36189 (24767 to 46152)	41252 (37492 to 44555)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From before dialysis at day of first study treatment (Day 0) to the end of the follow-up period (Day 112)

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Placebo

Reporting group description

Placebo once weekly intravenous over 5 weeks

Reporting group title

4 mg/kg BW PRS-080#022-DP

Reporting group description

4 mg/kg BW PRS-080#022-DP once weekly intravenous over 5 weeks

Reporting group title

8 mg/kg BW PRS-080#022-DP

Reporting group description

8 mg/kg BW PRS-080#022-DP once weekly intravenous over 5 weeks

Serious adverse events	Placebo	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
Additional description: Event was considered not related to study medication.
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
Additional description: Event was considered not related to study medication.
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Migraine
Additional description: Event was considered not related to study medication.
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
Additional description: Event was considered not related to study medication.
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Malnutrition
Additional description: Event was considered not related to study medication.
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Placebo	4 mg/kg BW PRS-080#022-DP	8 mg/kg BW PRS-080#022-DP
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	4 / 4 (100.00%)	4 / 4 (100.00%)
Vascular disorders
Hypertension
subjects affected / exposed	1 / 4 (25.00%)	2 / 4 (50.00%)	0 / 4 (0.00%)
occurrences all number	6	2	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)
occurrences all number	0	0	2
Oedema peripheral
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	4	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)
occurrences all number	0	1	1
Dyspnoea
subjects affected / exposed	2 / 4 (50.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	3	0	1
Nasal congestion
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Investigations
Body temperature increased
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	3	0
Haemoglobin decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Injury, poisoning and procedural complications
Laceration
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0
Post procedural haemorrhage
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Procedural hypotension
subjects affected / exposed	2 / 4 (50.00%)	2 / 4 (50.00%)	0 / 4 (0.00%)
occurrences all number	6	5	0
Procedural pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Cardiac disorders
Pericardial effusion
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0
Sinus tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Nervous system disorders
Carotid artery stenosis
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Headache
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	0	0
Phantom pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Restless legs syndrome
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Eye disorders
Blepharitis
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)
occurrences all number	0	1	1
Colitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Diarrhoea
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	1
Nausea
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Toothache
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Vomiting
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)
occurrences all number	1	0	4
Skin and subcutaneous tissue disorders
Decubitus ulcer
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Pruritus
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Pruritus generalised
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0
Renal and urinary disorders
Bladder hypertrophy
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Renal pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	1 / 4 (25.00%)	3 / 4 (75.00%)	2 / 4 (50.00%)
occurrences all number	1	16	4
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0
Infections and infestations
Conjunctivitis
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0
Localised infection
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Nasopharyngitis
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Pharyngitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Respiratory tract infection
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	1
Fluid overload
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Hyperkalaemia
subjects affected / exposed	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0
Hyperphosphataemia
subjects affected / exposed	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0

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Were there any global substantial amendments to the protocol? Yes

06 Dec 2017

Changes to v1.1: I) Time window to be on stable erythropoiesis-stimulating agent (ESA) dose before Screening was changed to ‘at the beginning of Screening’ (Inclusion Criterion 3); II) Time window to be on stable oral or intravenous iron doses before Screening was changed to ‘at the beginning of Screening’ (Inclusion Criterion 4). Additionally, it was specified, that iron was to be kept stable for a minimum of two weeks during the screening period before it was discontinued one week before the first treatment until Day 56 (one month follow-up); III) Inclusion Criterion serum ferritin concentration was changed to ≥200 ng/mL; IV) Screening serum folate and vitamin B12 below the lower limit of normal were allowed if the abnormal values were judged to be not clinically significant by the investigator; V) It was specified that glucose was no longer assessed as biochemistry parameter; VI) Body weight (BW) was to be assessed after dialysis at the day of the third hemoglobin (Hb) sample taken.

29 Mar 2018

Changes to v2.0: I) It was specified that slow pharmacodynamic (PD) parameters (Hb, reticulocyte count, reticulocyte hemoglobin) will be additionally assessed at Visits 3, 5, 8 and 10 (Days 7, 14, 21 and 28) before dialysis to ensure a better comparability to the pre-treatment samples which were taken before dialysis and to exclude a dialysis effect.

20 Sep 2018

Changes to v2.0 and Amendment No.1: I) Additional visits (i.e. at Days 4, 11, 25, and 32) and additional blood collections (i.e. at visit Day 18) to assess slow and fast PD and hepcidin were added; II) Additional blood collections to assess slow PD parameters at visits Day 2, 9, 16, and 23 added; III) History of malignancy was added as an exclusion criterion, recommended by the DSMB; IV) Sample size was increased to 13 patients. Hower, the planned unblinded assignment (placebo or study drug) of a 13th patient to cohort 2 (8 mg/kg BW) by the sponsor was not performed due to insufficient amount of the PRS-080#02-DP. Therefore, the study was terminated after 12 patients had completed the study.

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.

Two patients were treated with a one week delay due to investigation and resolution of particles detected while preparing infusion bags.

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Clinical trials

Clinical Trial Results:
Phase IIa study to evaluate the safety, pharmacokinetics, and pharmacodynamics of repeated administrations over 4 weeks of the hepcidin antagonist PRS-080#022-DP in anemic chronic kidney disease patients undergoing hemodialysis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Safety and tolerability

Primary: Safety and tolerability

Secondary: Pharmacokinetic end point Cmax

Secondary: Pharmacokinetic end point Cmax

Secondary: Pharmacokinetic end point Ctrough

Secondary: Pharmacokinetic end point Ctrough

Secondary: Pharmacokinetic end point tmax

Secondary: Pharmacokinetic end point tmax

Secondary: Pharmacodynamic end point changes in plasma hepcidin levels from baseline

Secondary: Pharmacodynamic end point changes in plasma hepcidin levels from baseline

Secondary: Pharmacodynamic end point AUC of serum iron

Secondary: Pharmacodynamic end point AUC of serum iron

Secondary: Pharmacodynamic end point AUC of transferin saturation in serum

Secondary: Pharmacodynamic end point AUC of transferin saturation in serum

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Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

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Clinical trials

Clinical Trial Results: Phase IIa study to evaluate the safety, pharmacokinetics, and pharmacodynamics of repeated administrations over 4 weeks of the hepcidin antagonist PRS-080#022-DP in anemic chronic kidney disease patients undergoing hemodialysis

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Safety and tolerability

Primary: Safety and tolerability

Secondary: Pharmacokinetic end point Cmax

Secondary: Pharmacokinetic end point Cmax

Secondary: Pharmacokinetic end point Ctrough

Secondary: Pharmacokinetic end point Ctrough

Secondary: Pharmacokinetic end point tmax

Secondary: Pharmacokinetic end point tmax

Secondary: Pharmacodynamic end point changes in plasma hepcidin levels from baseline

Secondary: Pharmacodynamic end point changes in plasma hepcidin levels from baseline

Secondary: Pharmacodynamic end point AUC of serum iron

Secondary: Pharmacodynamic end point AUC of serum iron

Secondary: Pharmacodynamic end point AUC of transferin saturation in serum

Secondary: Pharmacodynamic end point AUC of transferin saturation in serum

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Phase IIa study to evaluate the safety, pharmacokinetics, and pharmacodynamics of repeated administrations over 4 weeks of the hepcidin antagonist PRS-080#022-DP in anemic chronic kidney disease patients undergoing hemodialysis