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CompletedNCT03078582Updated Jul 27, 2022Results posted

Phase 2 Safety and Efficacy Study of Zilucoplan (RA101495) to Treat PNH Patients

A Phase 2 interventional study of Zilucoplan (RA101495) in Paroxysmal Nocturnal Hemoglobinuria (PNH), sponsored by Ra Pharmaceuticals. Completed at 12 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-07-27.

Sponsored by Ra Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
26
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of the study is to evaluate the safety and efficacy of zilucoplan (RA101495) in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). There will be two groups of patients in the study: the first group will include patients who have never received eculizumab for treatment of PNH. The second group will include patients who have received treatment with eculizumab for at least 6 months prior to the study. Patients will be treated with RA101495 for 12 weeks.

02

Conditions studied

  • Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

  • PNH
03

In context

Hemoglobinuria

107 studies on the registry are indexed under Hemoglobinuria; 10 are open to participants now.

This study's enrollment of 26 is close to the median of 27 across 89 interventional studies indexed under Hemoglobinuria.

Browse Hemoglobinuria studies →

Lead sponsor

Ra Pharmaceuticals is the lead sponsor of 4 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Diagnosis of PNH by flow cytometry
  • For treatment naive patients: subjects must not have received treatment with eculizumab prior to or during the Screening Period and must have a lactate dehydrogenase (LDH) level ≥2 times the upper limit of normal (xULN) during Screening
  • For patients who previously received eculizumab: subjects must have received treatment with eculizumab for at least 6 months prior to Screening

Exclusion criteria

Exclusion Criteria:

  • History of meningococcal disease
  • Current systemic infection or suspicion of active bacterial infection
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Zilucoplan (RA101495) treatment naive

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

    Drug: Zilucoplan (RA101495)

  • Experimental
    Zilucoplan (RA101495) previously on eculizumab

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

    Drug: Zilucoplan (RA101495)

Interventions

  • DrugZilucoplan (RA101495)

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

06

What researchers measure

Primary outcomes

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

    The primary efficacy endpoint is the change-from-baseline in serum LDH levels during this period, defined as the mean LDH values of Weeks 6, 8, 10, and 12 minus the baseline value of LDH.

    Time frame: Through Week 12 of the study

Secondary outcomes

  1. Changes From Baseline in Bilirubin Values

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

    Time frame: Through Week 12 of the study

  2. Total Hemoglobin

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

    Time frame: Through Week 12 of the Study

  3. Changes From Baseline in Free Hemoglobin Values

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

    Time frame: Through Week 12 of the study

  4. Haptoglobin Values

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

    Time frame: Through Week 12 of the Study

  5. Reticulocyte Values

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

    Time frame: Through Week 12 of the Study

  6. Hemoglobinuria Values

    Changes from baseline at each of the scheduled post-baseline 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.

    Time frame: Through Week 12 of the Study

07

Results

Posted Mar 10, 2020

Participant flow

Participant flow — Overall Study
MilestoneCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
Started1016
Completed108
Not completed08
Withdrew: Adverse event08

Outcome measures

PrimaryChange-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.

The primary efficacy endpoint is the change-from-baseline in serum LDH levels during this period, defined as the mean LDH values of Weeks 6, 8, 10, and 12 minus the baseline value of LDH.

Time frame:
Through Week 12 of the study
Reported as:
Mean · U/L
Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.
U/LCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.-695.2 ± 589.2216.7 ± 209.2
SecondaryChanges From Baseline in Bilirubin Values

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

Time frame:
Through Week 12 of the study
Reported as:
Mean · umol/L
Changes From Baseline in Bilirubin Values
umol/LCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
Week 11.3 ± 7.21.9 ± 4.5
Week 23.1 ± 7.74.4 ± 6.5
Week 34.4 ± 9.06.8 ± 7.5
Week 44.0 ± 6.74.3 ± 6.5
Week 64.1 ± 7.43.8 ± 7.8
Week 84.0 ± 6.14.4 ± 9.9
Week 105.7 ± 10.91.5 ± 6.1
Week 124.6 ± 11.80.9 ± 4.5
SecondaryTotal Hemoglobin

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

Time frame:
Through Week 12 of the Study
Reported as:
Mean · g/L
Total Hemoglobin
g/LCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
Week 1-1.5 ± 10.4-0.7 ± 7.1
Week 21.6 ± 7.40.9 ± 5.4
Week 34.3 ± 9.5-1.1 ± 9.0
Week 42.7 ± 10.5-0.9 ± 5.1
Week 63.6 ± 9.8-1.4 ± 5.3
Week 83.1 ± 9.6-1.0 ± 7.6
Week 104.5 ± 8.8-1.3 ± 8.7
Week 126.9 ± 10.60.5 ± 7.2
SecondaryChanges From Baseline in Free Hemoglobin Values

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

Time frame:
Through Week 12 of the study
Reported as:
Mean · mg/dL
Changes From Baseline in Free Hemoglobin Values
mg/dLCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
Week 1-7.84 ± 8.373.55 ± 18.51
Week 2-8.31 ± 9.07-1.00 ± 11.66
Week 3-5.65 ± 10.25-0.21 ± 3.87
Week 4-7.57 ± 8.1216.90 ± 50.64
Week 6-8.24 ± 9.19-3.53 ± 10.66
Week 8-7.62 ± 9.07-2.39 ± 9.25
Week 10-7.60 ± 9.03-2.02 ± 10.06
Week 12-7.39 ± 10.10-2.23 ± 11.32
SecondaryHaptoglobin Values

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

Time frame:
Through Week 12 of the Study
Reported as:
Mean · g/L
Haptoglobin Values
g/LCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
Week 10.090 ± 0.2850.010 ± 0.019
Week 20.080 ± 0.253-0.003 ± 0.007
Week 30.006 ± 0.019-0.003 ± 0.007
Week 40.012 ± 0.038-0.064 ± 0.180
Week 60.000 ± 0.000-0.064 ± 0.180
Week 80.004 ± 0.013-0.064 ± 0.180
Week 100.000 ± 0.000-0.064 ± 0.180
Week 120.000 ± 0.000-0.064 ± 0.180
SecondaryReticulocyte Values

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

Time frame:
Through Week 12 of the Study
Reported as:
Mean · 10^12 cells/L (SI Units)
Reticulocyte Values
10^12 cells/L (SI Units)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
Week 1-0.0113 ± 0.0494-0.0147 ± 0.0326
Week 2-0.0157 ± 0.05910.0022 ± 0.0279
Week 3-0.0099 ± 0.05840.0063 ± 0.0197
Week 4-0.0137 ± 0.04390.0004 ± 0.0289
Week 60.0000 ± 0.05380.0170 ± 0.0259
Week 8-0.0042 ± 0.06190.0050 ± 0.0346
Week 10-0.0060 ± 0.06080.0085 ± 0.0304
Week 12-0.0047 ± 0.05700.0061 ± 0.0166
SecondaryHemoglobinuria Values

Changes from baseline at each of the scheduled post-baseline 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.

Time frame:
Through Week 12 of the Study
Reported as:
Mean · score on a scale
Hemoglobinuria Values
score on a scaleCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
Week 1-0.2 ± 2.30.8 ± 1.8
Week 20.4 ± 2.20.1 ± 1.3
Week 30.3 ± 2.70.7 ± 1.8
Week 4-0.2 ± 2.00.4 ± 1.6
Week 60.3 ± 2.50.8 ± 2.3
Week 8-0.2 ± 2.30.3 ± 1.6
Week 100.3 ± 2.90.9 ± 1.6
Week 12-0.2 ± 2.90.0 ± 2.2

Adverse events

Collected over Through Week 12 of the study. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort A (Treatment Naive)0/10 (0%)2/10 (20%)10/10 (100%)
Cohort B (Previously on Eculizumab)0/16 (0%)1/16 (6.3%)15/16 (93.8%)
Most frequent serious events
Most frequent serious events
EventCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
PyrexiaGeneral disorders1/10—
Febrile nonhaemolytic transfusion reactionInjury, poisoning and procedural complications1/10—
Urinary tract InfectionInfections and infestations—1/16
Most frequent other events
Showing 10 of 55
Most frequent other events
EventCohort A (Treatment Naive)Cohort B (Previously on Eculizumab)
HaemolysisBlood and lymphatic system disorders0/107/16
HeadacheNervous system disorders1/107/16
Injection site bruisingGeneral disorders3/101/16
Upper respiratory tract infectionInfections and infestations3/101/16
Abdominal PainGastrointestinal disorders2/101/16
DizzinessNervous system disorders2/103/16
Oropharyngeal painRespiratory, thoracic and mediastinal disorders2/100/16
Abdominal Pain UpperGastrointestinal disorders0/103/16
FatigueGeneral disorders1/103/16
Back painMusculoskeletal and connective tissue disorders1/103/16

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)Total
<=18 years000
Between 18 and 65 years71118
>=65 years358
Age, Continuous
Age, Continuous(years)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)Total
Mean59.4 ± 14.549.6 ± 18.553.4 ± 17.4
Sex: Female, Male
Sex: Female, Male(Participants)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)Total
Female6713
Male4913
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)Total
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American022
White101424
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)Total
New Zealand404
Canada101
Hungary112
Finland123
Denmark011
United Kingdom235
Australia055
Germany145
Weight
Weight(kg)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)Total
Mean77.77 ± 20.6479.16 ± 14.8678.63 ± 16.92
Height
Height(cm)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)Total
Mean168.25 ± 11.08171.10 ± 8.69170.00 ± 9.56
BMI
BMI(kg/m2)Cohort A (Treatment Naive)Cohort B (Previously on Eculizumab)Total
Mean27.30 ± 6.1526.95 ± 4.1427.08 ± 4.89
08

Study locations

12 sites
  • Investigative Site
    Gosford, New South Wales, Australia
  • Investigative Site
    Parkville, Australia
  • Investigative Site
    Toronto, Ontario, Canada
  • Investigative Site
    Copenhagen, Denmark
  • Investigative Site
    Helsinki, Finland
  • Investigative Site
    Essen, Germany
  • Investigative Site
    Ulm, Germany
  • Investigative Site
    Budapest, Hungary
  • Investigative Site
    Christchurch, New Zealand
  • Investigative Site
    Hamilton, New Zealand
  • Investigative Site
    Leeds, United Kingdom
  • Investigative Site
    London, United Kingdom
09

References and documents

Related links

Study documents

  • Study protocol · Oct 20, 2016
  • Statistical analysis plan · Mar 22, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 27, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03078582
Lead sponsor
Ra Pharmaceuticals
Responsible party
Sponsor
First posted
Mar 13, 2017
Start date
Mar 8, 2017
Primary completion
Mar 28, 2018
Completion
Mar 28, 2018
Results posted
Mar 10, 2020
Last update
Jul 27, 2022

Study contacts

Dr. Anita Hill
principal investigator · St James' Institute of Oncology

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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