Title

Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients Who Have an Inadequate Response to Eculizumab
A Phase 2 Multicenter, Open-Label, Uncontrolled Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of RA101495 in Subjects With Paroxysmal Nocturnal Hemoglobinuria Who Have an Inadequate Response to Eculizumab
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    ra101495 ...
  • Study Participants

    3
The purpose of the study is to evaluate the safety and efficacy of RA101495 in patients with paroxysmal nocturnal hemoglobinuria (PNH) who have an inadequate response to eculizumab. Patients will be treated with RA101495 for 12 weeks.
Study Started
Apr 17
2017
Primary Completion
Mar 28
2018
Study Completion
Mar 28
2018
Results Posted
Feb 26
2020
Last Update
Jul 27
2022

Drug Zilucoplan (RA101495)

0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Zilucoplan (RA101495) Experimental

Subjects will receive RA101495 at the dose of 0.3 mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC

Criteria

Inclusion Criteria:

Diagnosis of PNH by flow cytometry
Inadequate response to eculizumab defined as having received eculizumab for at least 6 months plus a documented LDH level ≥ 1.5 x the upper limit of normal (ULN) and/or the presence of a known C5 mutation conferring resistance to eculizumab

Exclusion Criteria:

History of meningococcal disease
Current systemic infection or suspicion of active bacterial infection

Summary

Zilucoplan (RA101495)

All Events

Event Type Organ System Event Term Zilucoplan (RA101495)

Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Levels.

Change-from-baseline through Week 12 in serum lactate dehydrogenase (LDH) levels

Zilucoplan (RA101495)

100.3
U/L (Mean)
Standard Deviation: 128.0

Change-from-baseline Bilirubin Values

Changes from baseline at each of the scheduled postbaseline time-points

Zilucoplan (RA101495)

Week 1

-3.3
umol/L (Mean)
Standard Deviation: 5.1

Week 10

-7.7
umol/L (Mean)
Standard Deviation: 14.8

Week 12

-2.0
umol/L (Mean)
Standard Deviation: 6.2

Week 2

-4.7
umol/L (Mean)
Standard Deviation: 12.0

Week 3

-4.3
umol/L (Mean)
Standard Deviation: 7.5

Week 4

-0.3
umol/L (Mean)
Standard Deviation: 2.9

Week 6

-6.7
umol/L (Mean)
Standard Deviation: 17.5

Week 8

-2.3
umol/L (Mean)
Standard Deviation: 12.5

Change-from-baseline Total Hemoglobin Values

Changes from baseline at each of the scheduled postbaseline time-points

Zilucoplan (RA101495)

Week 1

5.7
g/L (Mean)
Standard Deviation: 4.2

Week 10

2.3
g/L (Mean)
Standard Deviation: 3.1

Week 12

0.3
g/L (Mean)
Standard Deviation: 2.5

Week 2

3.3
g/L (Mean)
Standard Deviation: 3.8

Week 3

0.3
g/L (Mean)
Standard Deviation: 4.0

Week 4

-0.3
g/L (Mean)
Standard Deviation: 7.2

Week 6

0.7
g/L (Mean)
Standard Deviation: 5.8

Week 8

-3.3
g/L (Mean)
Standard Deviation: 4.2

Change-from-baseline Free Hemoglobin Values

Changes from baseline at each of the scheduled postbaseline time-points

Zilucoplan (RA101495)

Week 1

-145.9
mg/dL

Week 10

-143.5
mg/dL

Week 12

-144.3
mg/dL

Week 2

-140.6
mg/dL

Week 3

-147.7
mg/dL

Week 4

-138.4
mg/dL

Week 6

-147.3
mg/dL

Week 8

-148.1
mg/dL

Change-from-baseline Haptoglobin Values

Changes from baseline at each of the scheduled postbaseline time-points

Zilucoplan (RA101495)

Week 1

Week 10

Week 12

Week 2

Week 3

Week 4

0.133
g/L (Mean)
Standard Deviation: 0.231

Week 6

Week 8

Change-from-baseline Reticulocyte Values

Changes from baseline at each of the scheduled postbaseline time-points

Zilucoplan (RA101495)

Week 1

-0.019
10^12 cells/L (Mean)
Standard Deviation: 0.0382

Week 10

0.035
10^12 cells/L (Mean)
Standard Deviation: 0.0350

Week 12

0.019
10^12 cells/L (Mean)
Standard Deviation: 0.0092

Week 2

0.009
10^12 cells/L (Mean)
Standard Deviation: 0.0052

Week 3

0.043
10^12 cells/L (Mean)
Standard Deviation: 0.0327

Week 4

0.0477
10^12 cells/L (Mean)
Standard Deviation: 0.0499

Week 6

0.031
10^12 cells/L (Mean)
Standard Deviation: 0.0157

Week 8

0.0253
10^12 cells/L (Mean)
Standard Deviation: 0.0248

Change-from-baseline Hemoglobinuria Values

Changes from baseline at each of the scheduled postbaseline time-points Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10. Where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria.

Zilucoplan (RA101495)

Week 1

Week 10

2.3
score on a scale (Mean)
Standard Deviation: 2.5

Week 12

-0.3
score on a scale (Mean)
Standard Deviation: 2.1

Week 2

0.5
score on a scale (Mean)
Standard Deviation: 0.7

Week 3

0.5
score on a scale (Mean)
Standard Deviation: 0.7

Week 4

1.0
score on a scale (Mean)
Standard Deviation: 1.4

Week 6

0.5
score on a scale (Mean)
Standard Deviation: 0.7

Week 8

2.0
score on a scale (Mean)
Standard Deviation: None

Age, Continuous

35.3
years (Mean)
Standard Deviation: 16.3

BMI

35.72
kg/m2 (Mean)
Standard Deviation: 7.76

Height

176.20
cm (Mean)
Standard Deviation: 7.60

Weight

109.67
kg (Mean)
Standard Deviation: 13.97

Age, Categorical

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Sex: Female, Male

Overall Study

Zilucoplan (RA101495)