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Dose-Escalation Study of ALXN1210 IV in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH)

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ClinicalTrials.gov Identifier: NCT02598583
Recruitment Status : Active, not recruiting
First Posted : November 6, 2015
Results First Posted : January 30, 2018
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition PNH
Intervention Biological: ALXN1210
Enrollment 13
Recruitment Details  
Pre-assignment Details  
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description

Induction phase: a) 400 milligram (mg) on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Period Title: Overall Study
Started 6 7
Completed [1] 6 7
Not Completed 0 0
[1]
Completed 169-day Primary Evaluation Period.
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2 Total
Hide Arm/Group Description

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Total of all reporting groups
Overall Number of Baseline Participants 6 7 13
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 7 participants 13 participants
41.1  (10.87) 43.6  (13.48) 42.4  (11.91)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 7 participants 13 participants
Female
2
  33.3%
5
  71.4%
7
  53.8%
Male
4
  66.7%
2
  28.6%
6
  46.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 7 participants 13 participants
Asian
6
 100.0%
6
  85.7%
12
  92.3%
White
0
   0.0%
1
  14.3%
1
   7.7%
1.Primary Outcome
Title Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169
Hide Description Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.
Time Frame Baseline, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all enrolled participants who received at least 1 dose of ALXN1210 and who had a Baseline measurement with at least 1 LDH measurement post-first ALXN1210 dose. Data were summarized only for participants with assessment at Baseline and the specified time point.
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description:

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: Percent change
-85.952  (3.1897) -84.736  (3.7736)
2.Secondary Outcome
Title Percent Change In Free Hemoglobin Levels From Baseline To Day 169
Hide Description Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame Baseline, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all enrolled participants who received at least 1 dose of ALXN1210 and who had a Baseline measurement with at least 1 free hemoglobin measurement post-first ALXN1210 dose. Data were summarized only for participants with assessment at Baseline and the specified time point.
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description:

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: Percent change
-22.335  (42.2249) -43.969  (24.7674)
3.Secondary Outcome
Title Percent Change In Haptoglobin Levels From Baseline To Day 169
Hide Description Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame Baseline, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all enrolled participants who received at least 1 dose of ALXN1210 and who had a Baseline measurement with at least 1 haptoglobin measurement post-first ALXN1210 dose. Data were summarized only for participants with assessment at Baseline and the specified time point.
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description:

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: Percent change
40.0000  (55.13620) 17.1429  (45.35574)
4.Secondary Outcome
Title Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169
Hide Description Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame Baseline, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all enrolled participants who received at least 1 dose of ALXN1210 and who had a Baseline measurement with at least 1 reticulocyte/erythrocyte count measurement post-first ALXN1210 dose. Data were summarized only for participants with assessment at Baseline and the specified time point.
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description:

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: Percent change
-21.203  (14.1461) 28.784  (54.2636)
5.Secondary Outcome
Title Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169
Hide Description Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame Baseline, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all enrolled participants who received at least 1 dose of ALXN1210 and who had a Baseline measurement with at least 1 PNH RBC clones measurement post-first ALXN1210 dose. Data were summarized only for participants with assessment at Baseline and the specified time point.
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description:

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: Percent change
7.873  (19.3064) 25.840  (62.9677)
6.Secondary Outcome
Title Percent Change In D-dimer Levels From Baseline To Day 169
Hide Description Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time Frame Baseline, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all enrolled participants who received at least 1 dose of ALXN1210 and who had a Baseline measurement with at least 1 D-dimer measurement post-first ALXN1210 dose. Data were summarized only for participants with assessment at Baseline and the specified time point.
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description:

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: Percent change
-27.42  (40.015) -0.49  (73.116)
7.Secondary Outcome
Title Change In Clinical Manifestations Of PNH From Baseline To Day 169
Hide Description Clinical manifestations are defined as fatigue, abdominal pain, dyspnea, dysphagia, chest pain, and erectile dysfunction (ED) by cohort. Improvement is defined as present at baseline and absent at Day 169 endpoint. Worsening is defined as absent at Baseline and present at Day 169 endpoint.
Time Frame Baseline, Day 169
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set included all enrolled participants who received at least 1 dose of ALXN1210 and who had a Baseline measurement with at least 1 clinical manifestation of PNH assessed post-first ALXN1210 dose. Data were summarized only for participants with assessment at Baseline and the specified time point. ED affects only male participants.
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description:

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

Overall Number of Participants Analyzed 6 7
Measure Type: Count of Participants
Unit of Measure: Participants
Fatigue Improved from Baseline to Day 169
1
  16.7%
1
  14.3%
Worsened from Baseline to Day 169
0
   0.0%
0
   0.0%
No Change/Not Applicable
5
  83.3%
6
  85.7%
Abdominal pain Improved from Baseline to Day 169
0
   0.0%
3
  42.9%
Worsened from Baseline to Day 169
0
   0.0%
0
   0.0%
No Change/Not Applicable
6
 100.0%
4
  57.1%
Dyspnoea Improved from Baseline to Day 169
2
  33.3%
1
  14.3%
Worsened from Baseline to Day 169
0
   0.0%
0
   0.0%
No Change/Not Applicable
4
  66.7%
6
  85.7%
Dysphagia Improved from Baseline to Day 169
0
   0.0%
1
  14.3%
Worsened from Baseline to Day 169
0
   0.0%
0
   0.0%
No Change/Not Applicable
6
 100.0%
6
  85.7%
Chest pain Improved from Baseline to Day 169
0
   0.0%
2
  28.6%
Worsened from Baseline to Day 169
0
   0.0%
0
   0.0%
No Change/Not Applicable
6
 100.0%
5
  71.4%
ED Improved from Baseline to Day 169
1
  16.7%
0
   0.0%
Worsened from Baseline to Day 169
0
   0.0%
0
   0.0%
No Change/Not Applicable
5
  83.3%
7
 100.0%
Time Frame After first dose of study drug on Day 1 through Day 169
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ALXN1210 Cohort 1 ALXN1210 Cohort 2
Hide Arm/Group Description

Induction phase: a) 400 mg on Day 1 and Day 8, 600 mg on Day 15; or b) 600 mg on Day 1, 600 mg on Day 15

Maintenance phase: the first of 5 doses of 900 mg on Day 29 and every 4 weeks thereafter

Induction phase: 600 mg on Day 1, 900 mg on Day 15

Maintenance phase: the first of 5 doses of 1800 mg on Day 29 and every 4 weeks thereafter

All-Cause Mortality
ALXN1210 Cohort 1 ALXN1210 Cohort 2
Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/7 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
ALXN1210 Cohort 1 ALXN1210 Cohort 2
Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)   0/7 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
ALXN1210 Cohort 1 ALXN1210 Cohort 2
Affected / at Risk (%) Affected / at Risk (%)
Total   5/6 (83.33%)   7/7 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  1/6 (16.67%)  0/7 (0.00%) 
Cardiac disorders     
Atrial flutter  1  0/6 (0.00%)  1/7 (14.29%) 
Gastrointestinal disorders     
Abdominal pain  1  1/6 (16.67%)  1/7 (14.29%) 
Constipation  1  1/6 (16.67%)  1/7 (14.29%) 
Nausea  1  1/6 (16.67%)  1/7 (14.29%) 
Vomiting  1  1/6 (16.67%)  1/7 (14.29%) 
Dyspepsia  1  1/6 (16.67%)  0/7 (0.00%) 
Enterocolitis  1  0/6 (0.00%)  1/7 (14.29%) 
Toothache  1  0/6 (0.00%)  1/7 (14.29%) 
General disorders     
Fatigue  1  2/6 (33.33%)  0/7 (0.00%) 
Oedema peripheral  1  1/6 (16.67%)  0/7 (0.00%) 
Pain  1  0/6 (0.00%)  1/7 (14.29%) 
Pyrexia  1  1/6 (16.67%)  0/7 (0.00%) 
Infections and infestations     
Upper respiratory tract infection  1  2/6 (33.33%)  2/7 (28.57%) 
Hordeolum  1  0/6 (0.00%)  2/7 (28.57%) 
Nasopharyngitis  1  0/6 (0.00%)  1/7 (14.29%) 
Laryngitis  1  0/6 (0.00%)  1/7 (14.29%) 
Pharyngitis  1  0/6 (0.00%)  1/7 (14.29%) 
Viral upper respiratory tract infection  1  0/6 (0.00%)  1/7 (14.29%) 
Investigations     
Blood bilirubin increased  1  1/6 (16.67%)  0/7 (0.00%) 
Blood creatinine increased  1  1/6 (16.67%)  0/7 (0.00%) 
Neutrophil count decreased  1  0/6 (0.00%)  1/7 (14.29%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/6 (0.00%)  1/7 (14.29%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/6 (16.67%)  1/7 (14.29%) 
Bone pain  1  0/6 (0.00%)  1/7 (14.29%) 
Joint range of motion decreased  1  1/6 (16.67%)  0/7 (0.00%) 
Nervous system disorders     
Headache  1  2/6 (33.33%)  2/7 (28.57%) 
Dizziness  1  2/6 (33.33%)  0/7 (0.00%) 
Neuropathy peripheral  1  1/6 (16.67%)  0/7 (0.00%) 
Presyncope  1  0/6 (0.00%)  1/7 (14.29%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/6 (16.67%)  1/7 (14.29%) 
Reflux laryngitis  1  0/6 (0.00%)  1/7 (14.29%) 
Cough  1  1/6 (16.67%)  0/7 (0.00%) 
Vascular disorders     
Hot flush  1  0/6 (0.00%)  1/7 (14.29%) 
1
Term from vocabulary, MedDRA (18.1)
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Alexion Pharmaceuticals, Inc.
Organization: Alexion Pharmaceuticals, Inc.
Phone: 855-752-2356
EMail: clinicaltrials@alexion.com
Layout table for additonal information
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02598583     History of Changes
Other Study ID Numbers: ALXN1210-PNH-103
First Submitted: November 2, 2015
First Posted: November 6, 2015
Results First Submitted: October 30, 2017
Results First Posted: January 30, 2018
Last Update Posted: June 4, 2019