Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03078582
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03078582
Recruitment Status : Completed
First Posted : March 13, 2017
Results First Posted : March 10, 2020
Last Update Posted : March 10, 2020
Sponsor:
Information provided by (Responsible Party):
Ra Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Paroxysmal Nocturnal Hemoglobinuria (PNH)
Intervention Drug: Zilucoplan (RA101495)
Enrollment 26
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Period Title: Overall Study
Started 10 16
Completed 10 8
Not Completed 0 8
Reason Not Completed
Adverse Event             0             8
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab) Total
Hide Arm/Group Description 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC Total of all reporting groups
Overall Number of Baseline Participants 10 16 26
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 16 participants 26 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
7
  70.0%
11
  68.8%
18
  69.2%
>=65 years
3
  30.0%
5
  31.3%
8
  30.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 16 participants 26 participants
59.4  (14.5) 49.6  (18.5) 53.4  (17.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 16 participants 26 participants
Female
6
  60.0%
7
  43.8%
13
  50.0%
Male
4
  40.0%
9
  56.3%
13
  50.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 16 participants 26 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
  12.5%
2
   7.7%
White
10
 100.0%
14
  87.5%
24
  92.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 10 participants 16 participants 26 participants
New Zealand 4 0 4
Canada 1 0 1
Hungary 1 1 2
Finland 1 2 3
Denmark 0 1 1
United Kingdom 2 3 5
Australia 0 5 5
Germany 1 4 5
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 10 participants 16 participants 26 participants
77.77  (20.64) 79.16  (14.86) 78.63  (16.92)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 10 participants 16 participants 26 participants
168.25  (11.08) 171.10  (8.69) 170.00  (9.56)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 10 participants 16 participants 26 participants
27.30  (6.15) 26.95  (4.14) 27.08  (4.89)
1.Primary Outcome
Title Change-from-baseline in Serum Lactate Dehydrogenase (LDH) Level.
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description:
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: U/L
-695.2  (589.2) 216.7  (209.2)
2.Secondary Outcome
Title Changes From Baseline in Bilirubin Values
Hide Description Changes from baseline at each of the scheduled post-baseline time-points
Time Frame Through Week 12 of the study
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description:
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: umol/L
Week 1 Number Analyzed 10 participants 7 participants
1.3  (7.2) 1.9  (4.5)
Week 2 Number Analyzed 10 participants 8 participants
3.1  (7.7) 4.4  (6.5)
Week 3 Number Analyzed 10 participants 8 participants
4.4  (9.0) 6.8  (7.5)
Week 4 Number Analyzed 10 participants 8 participants
4.0  (6.7) 4.3  (6.5)
Week 6 Number Analyzed 10 participants 8 participants
4.1  (7.4) 3.8  (7.8)
Week 8 Number Analyzed 10 participants 8 participants
4.0  (6.1) 4.4  (9.9)
Week 10 Number Analyzed 10 participants 8 participants
5.7  (10.9) 1.5  (6.1)
Week 12 Number Analyzed 10 participants 8 participants
4.6  (11.8) 0.9  (4.5)
3.Secondary Outcome
Title Total Hemoglobin
Hide Description Changes from baseline at each of the scheduled post-baseline time-points
Time Frame Through Week 12 of the Study
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description:
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: g/L
Week 1 Number Analyzed 10 participants 7 participants
-1.5  (10.4) -0.7  (7.1)
Week 2 Number Analyzed 10 participants 8 participants
1.6  (7.4) 0.9  (5.4)
Week 3 Number Analyzed 10 participants 8 participants
4.3  (9.5) -1.1  (9.0)
Week 4 Number Analyzed 10 participants 8 participants
2.7  (10.5) -0.9  (5.1)
Week 6 Number Analyzed 10 participants 8 participants
3.6  (9.8) -1.4  (5.3)
Week 8 Number Analyzed 10 participants 8 participants
3.1  (9.6) -1.0  (7.6)
Week 10 Number Analyzed 10 participants 8 participants
4.5  (8.8) -1.3  (8.7)
Week 12 Number Analyzed 10 participants 8 participants
6.9  (10.6) 0.5  (7.2)
4.Secondary Outcome
Title Changes From Baseline in Free Hemoglobin Values
Hide Description Changes from baseline at each of the scheduled post-baseline time-points
Time Frame Through Week 12 of the study
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description:
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: mg/dL
Week 1 Number Analyzed 8 participants 8 participants
-7.84  (8.37) 3.55  (18.51)
Week 2 Number Analyzed 9 participants 8 participants
-8.31  (9.07) -1.00  (11.66)
Week 3 Number Analyzed 8 participants 8 participants
-5.65  (10.25) -0.21  (3.87)
Week 4 Number Analyzed 9 participants 8 participants
-7.57  (8.12) 16.90  (50.64)
Week 6 Number Analyzed 8 participants 7 participants
-8.24  (9.19) -3.53  (10.66)
Week 8 Number Analyzed 9 participants 8 participants
-7.62  (9.07) -2.39  (9.25)
Week 10 Number Analyzed 9 participants 8 participants
-7.60  (9.03) -2.02  (10.06)
Week 12 Number Analyzed 8 participants 7 participants
-7.39  (10.10) -2.23  (11.32)
5.Secondary Outcome
Title Haptoglobin Values
Hide Description Changes from baseline at each of the scheduled post-baseline time-points
Time Frame Through Week 12 of the Study
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description:
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: g/L
Week 1 0.090  (0.285) 0.010  (0.019)
Week 2 0.080  (0.253) -0.003  (0.007)
Week 3 0.006  (0.019) -0.003  (0.007)
Week 4 0.012  (0.038) -0.064  (0.180)
Week 6 0.000  (0.000) -0.064  (0.180)
Week 8 0.004  (0.013) -0.064  (0.180)
Week 10 0.000  (0.000) -0.064  (0.180)
Week 12 0.000  (0.000) -0.064  (0.180)
6.Secondary Outcome
Title Reticulocyte Values
Hide Description Changes from baseline at each of the scheduled post-baseline time-points
Time Frame Through Week 12 of the Study
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description:
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: 10^12 cells/L (SI Units)
Week 1 Number Analyzed 10 participants 7 participants
-0.0113  (0.0494) -0.0147  (0.0326)
Week 2 Number Analyzed 10 participants 8 participants
-0.0157  (0.0591) 0.0022  (0.0279)
Week 3 Number Analyzed 10 participants 8 participants
-0.0099  (0.0584) 0.0063  (0.0197)
Week 4 Number Analyzed 10 participants 8 participants
-0.0137  (0.0439) 0.0004  (0.0289)
Week 6 Number Analyzed 10 participants 8 participants
0.0000  (0.0538) 0.0170  (0.0259)
Week 8 Number Analyzed 10 participants 8 participants
-0.0042  (0.0619) 0.0050  (0.0346)
Week 10 Number Analyzed 10 participants 8 participants
-0.0060  (0.0608) 0.0085  (0.0304)
Week 12 Number Analyzed 10 participants 8 participants
-0.0047  (0.0570) 0.0061  (0.0166)
7.Secondary Outcome
Title Hemoglobinuria Values
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description:
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
Overall Number of Participants Analyzed 10 8
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 1 Number Analyzed 9 participants 8 participants
-0.2  (2.3) 0.8  (1.8)
Week 2 Number Analyzed 10 participants 7 participants
0.4  (2.2) 0.1  (1.3)
Week 3 Number Analyzed 10 participants 7 participants
0.3  (2.7) 0.7  (1.8)
Week 4 Number Analyzed 9 participants 8 participants
-0.2  (2.0) 0.4  (1.6)
Week 6 Number Analyzed 10 participants 8 participants
0.3  (2.5) 0.8  (2.3)
Week 8 Number Analyzed 10 participants 8 participants
-0.2  (2.3) 0.3  (1.6)
Week 10 Number Analyzed 10 participants 8 participants
0.3  (2.9) 0.9  (1.6)
Week 12 Number Analyzed 10 participants 7 participants
-0.2  (2.9) 0.0  (2.2)
Time Frame Through Week 12 of the study
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Hide Arm/Group Description 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC 0.3mg/kg subcutaneously (SC) at Day 1 (loading dose) followed by a starting maintenance dose of 0.1 mg/kg daily SC
All-Cause Mortality
Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)      0/16 (0.00%)    
Hide Serious Adverse Events
Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/10 (20.00%)      1/16 (6.25%)    
General disorders     
Pyrexia  [1]  1/10 (10.00%)  1 0/0  0
Infections and infestations     
Urinary tract Infection   0/0  0 1/16 (6.25%)  1
Injury, poisoning and procedural complications     
Febrile nonhaemolytic transfusion reaction   1/10 (10.00%)  1 0/0  0
Indicates events were collected by systematic assessment
[1]
General disorders and administration site conditions
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort A (Treatment Naive) Cohort B (Previously on Eculizumab)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      15/16 (93.75%)    
Blood and lymphatic system disorders     
Haemolysis   0/10 (0.00%)  0 7/16 (43.75%)  7
Anaemia   0/10 (0.00%)  0 1/16 (6.25%)  1
Gastrointestinal disorders     
Abdominal Pain   2/10 (20.00%)  2 1/16 (6.25%)  3
Abdominal Pain Upper   0/10 (0.00%)  0 3/16 (18.75%)  3
Diarrhoea   1/10 (10.00%)  1 1/16 (6.25%)  1
Constipation   0/10 (0.00%)  0 1/16 (6.25%)  1
Enteritis   1/10 (10.00%)  1 0/16 (0.00%)  0
Nausea   0/10 (0.00%)  0 1/16 (6.25%)  1
Proctalgia   1/10 (10.00%)  1 0/16 (0.00%)  0
Vomiting   0/10 (0.00%)  0 1/16 (6.25%)  1
General disorders     
Fatigue   1/10 (10.00%)  1 3/16 (18.75%)  3
Injection site bruising   3/10 (30.00%)  3 1/16 (6.25%)  1
Asthenia   1/10 (10.00%)  1 0/16 (0.00%)  0
Chest pain   0/10 (0.00%)  0 1/16 (6.25%)  1
Crepitations   1/10 (10.00%)  1 0/16 (0.00%)  0
Influenza like illness   0/10 (0.00%)  0 1/16 (6.25%)  1
Vaccination site pain   1/10 (10.00%)  1 0/16 (0.00%)  0
Infections and infestations     
Upper respiratory tract infection   3/10 (30.00%)  3 1/16 (6.25%)  1
Localised infection   0/10 (0.00%)  0 1/16 (6.25%)  1
Rhinitis   0/10 (0.00%)  0 1/16 (6.25%)  1
Urosepsis   1/10 (10.00%)  1 0/16 (0.00%)  0
Vulvovaginal mycotic infection   1/10 (10.00%)  1 0/16 (0.00%)  0
Injury, poisoning and procedural complications     
Contusion   1/10 (10.00%)  1 0/16 (0.00%)  0
Febrile nonhaemolytic transfusion reaction   0/10 (0.00%)  0 1/16 (6.25%)  1
Tooth fracture   0/10 (0.00%)  0 1/16 (6.25%)  1
Investigations     
Blood glucose fluctuation   1/10 (10.00%)  1 0/16 (0.00%)  0
Blood lactate dehydrogenase increased   0/10 (0.00%)  0 1/16 (6.25%)  1
Haemoglobin decreased   1/10 (10.00%)  1 0/16 (0.00%)  0
Liver function test increased   1/10 (10.00%)  1 0/16 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite   1/10 (10.00%)  1 0/16 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain   1/10 (10.00%)  2 3/16 (18.75%)  6
Arthralgia   0/10 (0.00%)  0 2/16 (12.50%)  2
Pain in extremity   0/10 (0.00%)  0 2/16 (12.50%)  3
Flank pain   1/10 (10.00%)  1 0/16 (0.00%)  0
Musculoskeletal chest pain   0/10 (0.00%)  0 1/16 (6.25%)  2
Musculoskeletal pain   1/10 (10.00%)  2 0/16 (0.00%)  0
Myalgia   0/10 (0.00%)  0 1/16 (6.25%)  1
Nervous system disorders     
Headache   1/10 (10.00%)  3 7/16 (43.75%)  17
Dizziness   2/10 (20.00%)  2 3/16 (18.75%)  3
Dysgeusia   1/10 (10.00%)  1 0/16 (0.00%)  0
Presyncope   0/10 (0.00%)  0 1/16 (6.25%)  1
Syncope   1/10 (10.00%)  2 0/16 (0.00%)  0
Product Issues     
Device failure   0/10 (0.00%)  0 1/16 (6.25%)  1
Psychiatric disorders     
Agitation   0/10 (0.00%)  0 1/16 (6.25%)  1
Anxiety   1/10 (10.00%)  1 0/16 (0.00%)  0
Insomnia   0/10 (0.00%)  0 1/16 (6.25%)  1
Sleep disorder   1/10 (10.00%)  2 0/16 (0.00%)  0
Renal and urinary disorders     
Paroxysmal nocturnal haemoglobinuria   1/10 (10.00%)  1 2/16 (12.50%)  2
Reproductive system and breast disorders     
Vaginal discharge   0/10 (0.00%)  0 1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain   2/10 (20.00%)  2 0/16 (0.00%)  0
Cough   1/10 (10.00%)  1 0/16 (0.00%)  0
Dyspnoea   1/10 (10.00%)  1 0/16 (0.00%)  0
Epistaxis   0/10 (0.00%)  0 1/16 (6.25%)  4
Skin and subcutaneous tissue disorders     
Actinic keratosis   1/10 (10.00%)  1 0/16 (0.00%)  0
Vascular disorders     
Lymphoedema   1/10 (10.00%)  1 0/16 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Disclosure agreements are negotiated separately with each PI.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Sponsor Ra Pharmaceuticals, Inc.
Organization: Ra Pharmaceuticals, Inc
Phone: +1 617 401 4060
EMail: trials@rapharma.com
Layout table for additonal information
Responsible Party: Ra Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03078582    
Other Study ID Numbers: RA101495-01.201
2016-003522-16 ( EudraCT Number )
First Submitted: March 8, 2017
First Posted: March 13, 2017
Results First Submitted: June 19, 2019
Results First Posted: March 10, 2020
Last Update Posted: March 10, 2020