PNH
Conditions
Keywords
Paroxysmal Nocturnal Hemoglobinuria, PNH, complement inhibitor
Brief summary
This study evaluated the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of multiple intravenous (IV) doses of ALXN1210 administered to participants with PNH who have not previously been treated with complement inhibitor.
Detailed description
The data presented is up to the Primary Completion date of the study and is for the 24-week Primary Evaluation period. The study also includes an Extension Period of up to 5 years.
Interventions
BIOLOGICALALXN1210
Participants were administered ravulizumab as an IV infusion every 4 weeks.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female ≥18 years of age 2. PNH diagnosis confirmed by documented high-sensitivity flow cytometry 3. Documented meningococcal vaccination not more than 3 years prior to dosing 4. Female participants of childbearing potential used highly effective contraception starting at screening and continuing until at least 24-weeks after the last dose of ALXN1210 5. Willing and able to give written informed consent and comply with the study visit schedule
Exclusion criteria
1. Treatment with a complement inhibitor at any time 2. Females who were pregnant, breastfeeding or who had a positive pregnancy test at screening or Day 1 3. Participation in an interventional clinical study within 30 days before initiation of dosing on Day 1, or use of any experimental therapy within 30 days prior to dosing on Day 1, or within 5 half-lives of the product, whichever is greater 4. History of allergy to excipients of ALXN1210 or known allergy to Chinese hamster ovary cell proteins 5. Inability to comply with study requirements 6. History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the Investigator's judgment, would preclude participation 7. Other unspecified reasons that, in the opinion of the Investigator or Sponsor, made the participant unsuitable for enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169 | Baseline, Day 169 | Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change In Total C5 Concentration From Baseline To Day 1709 | Baseline, Day 1709 | — |
| Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821 | Baseline, Day 169, Day 1821 | Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion. |
| Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821 | Baseline, Day 169, Day 1821 | Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion. |
| Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821 | Baseline, Day 169, Day 1821 | Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion. |
| Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933 | Baseline, Day 169, Day 1933 | Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion. |
| Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821 | Baseline, Day 169, Day 1821 | Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion. |
| Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Baseline, Day 169, Day 1821 | 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. |
| Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1 | Day 1 | AUCt reported in hours\*microgram/milliliter (h\*ug/mL). |
| Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709 | Baseline, Day 1709 | — |
| Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141 | Day 141 | — |
| AUCtau/D At Day 141 | Day 141 | — |
| Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141 | Day 1 and Day 141 | — |
| Cmax/D At Day 1 And Day 141 | Day 1 and Day 141 | — |
| Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141 | Day 1 and Day 141 | — |
| Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141 | Day 1 and Day 141 | — |
| Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709 | Baseline, Day 1709 | — |
| Participants Experiencing Antidrug Antibodies (ADAs) | Day 1821 | — |
| AUCt/ Dose-normalized (D) At Day 1 | Day 1 | — |
Countries
Australia, South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ALXN1210 Cohort 1 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 | 6 |
| ALXN1210 Cohort 2 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 | 7 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Period | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | ALXN1210 Cohort 2 | Total | ALXN1210 Cohort 1 |
|---|---|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 13.48 | 42.4 years STANDARD_DEVIATION 11.91 | 41.1 years STANDARD_DEVIATION 10.87 |
| Race/Ethnicity, Customized Asian | 6 participants | 12 participants | 6 participants |
| Race/Ethnicity, Customized White | 1 participants | 1 participants | 0 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 3 / 6 | 4 / 7 |
Outcome results
Primary
Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169
Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.
Time frame: Baseline, Day 169
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169 | -85.952 percent change | Standard Deviation 3.1897 |
| ALXN1210 Cohort 2 | Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169 | -84.736 percent change | Standard Deviation 3.7736 |
Secondary
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141
Time frame: Day 141
Population: PK Analysis Set: all participants who had sufficient serum concentration data to enable the calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141 | 216515.22 h*ug/mL | Standard Deviation 68099.982 |
| ALXN1210 Cohort 2 | Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141 | 217936.47 h*ug/mL | Standard Deviation 31023.979 |
Secondary
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1
AUCt reported in hours\*microgram/milliliter (h\*ug/mL).
Time frame: Day 1
Population: Pharmacokinetics (PK) Analysis Set: all participants who had sufficient serum concentration data to enable the calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1 | 14273.95 h*ug/mL | Standard Deviation 4907.438 |
| ALXN1210 Cohort 2 | Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1 | 42366.62 h*ug/mL | Standard Deviation 3710.12 |
Secondary
AUCtau/D At Day 141
Time frame: Day 141
Population: PK Analysis Set: all participants who had sufficient serum concentration data to enable the calculation of PK parameters
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | AUCtau/D At Day 141 | 240.57 h*ug/mL/mg | Standard Deviation 75.667 |
| ALXN1210 Cohort 2 | AUCtau/D At Day 141 | 242.15 h*ug/mL/mg | Standard Deviation 34.471 |
Secondary
AUCt/ Dose-normalized (D) At Day 1
Time frame: Day 1
Population: PK Analysis Set: all participants who had sufficient serum concentration data to enable the calculation of PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | AUCt/ Dose-normalized (D) At Day 1 | 35.68 h*ug/mL/mg | Standard Deviation 12.269 |
| ALXN1210 Cohort 2 | AUCt/ Dose-normalized (D) At Day 1 | 70.61 h*ug/mL/mg | Standard Deviation 6.184 |
Secondary
Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821
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, Day 1821
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 1821 | No Change/Not Applicable | 3 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 169 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 1821 | Improved from Baseline | 2 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 169 | No Change/Not Applicable | 6 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 169 | No Change/Not Applicable | 6 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 1821 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 1821 | No Change/Not Applicable | 5 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 169 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 1821 | No Change/Not Applicable | 5 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 169 | No Change/Not Applicable | 6 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 169 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 1821 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 169 | Improved from Baseline | 2 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 1821 | No Change/Not Applicable | 5 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 1821 | No Change/Not Applicable | 3 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 169 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 169 | No Change/Not Applicable | 4 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 169 | No Change/Not Applicable | 5 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 169 | No Change/Not Applicable | 5 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 1821 | Improved from Baseline | 2 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 1821 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 169 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 1821 | No Change/Not Applicable | 3 Participants |
| ALXN1210 Cohort 1 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 1821 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 1821 | No Change/Not Applicable | 1 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 169 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 1821 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 169 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 169 | No Change/Not Applicable | 6 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 1821 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Fatigue: Day 1821 | No Change/Not Applicable | 3 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 169 | Improved from Baseline | 3 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 169 | No Change/Not Applicable | 4 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 1821 | Improved from Baseline | 2 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 1821 | No Change/Not Applicable | 2 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 169 | No Change/Not Applicable | 6 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 1821 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dyspnoea: Day 1821 | No Change/Not Applicable | 3 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 169 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 169 | No Change/Not Applicable | 6 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Dysphagia: Day 1821 | No Change/Not Applicable | 4 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 169 | Improved from Baseline | 2 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 169 | No Change/Not Applicable | 5 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 1821 | Improved from Baseline | 1 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Chest pain: Day 1821 | No Change/Not Applicable | 3 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 169 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 169 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 169 | No Change/Not Applicable | 7 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 1821 | Improved from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | ED: Day 1821 | Worsened from Baseline | 0 Participants |
| ALXN1210 Cohort 2 | Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 | Abdominal pain: Day 1821 | Worsened from Baseline | 0 Participants |
Secondary
Cmax/D At Day 1 And Day 141
Time frame: Day 1 and Day 141
Population: PK Analysis Set: all participants who had sufficient serum concentration data to enable the calculation of PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Cmax/D At Day 1 And Day 141 | Day 1 | 0.29 ug/mL/mg | Standard Deviation 0.039 |
| ALXN1210 Cohort 1 | Cmax/D At Day 1 And Day 141 | Day 141 | 0.57 ug/mL/mg | Standard Deviation 0.163 |
| ALXN1210 Cohort 2 | Cmax/D At Day 1 And Day 141 | Day 1 | 0.34 ug/mL/mg | Standard Deviation 0.017 |
| ALXN1210 Cohort 2 | Cmax/D At Day 1 And Day 141 | Day 141 | 0.57 ug/mL/mg | Standard Deviation 0.072 |
Secondary
Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141
Time frame: Day 1 and Day 141
Population: PK Analysis Set: all participants who had sufficient serum concentration data to enable the calculation of PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141 | Day 1 | 73.25 ug/mL | Standard Deviation 18.173 |
| ALXN1210 Cohort 1 | Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141 | Day 141 | 243.50 ug/mL | Standard Deviation 126.572 |
| ALXN1210 Cohort 2 | Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141 | Day 1 | 80.50 ug/mL | Standard Deviation 6.541 |
| ALXN1210 Cohort 2 | Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141 | Day 141 | 204.00 ug/mL | Standard Deviation 56.586 |
Secondary
Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141
Time frame: Day 1 and Day 141
Population: PK Analysis Set: all participants who had sufficient serum concentration data to enable the calculation of PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141 | Day 1 | 114.00 ug/mL | Standard Deviation 15.556 |
| ALXN1210 Cohort 1 | Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141 | Day 141 | 514.00 ug/mL | Standard Deviation 147.078 |
| ALXN1210 Cohort 2 | Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141 | Day 1 | 203.50 ug/mL | Standard Deviation 10.279 |
| ALXN1210 Cohort 2 | Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141 | Day 141 | 512.25 ug/mL | Standard Deviation 64.958 |
Secondary
Participants Experiencing Antidrug Antibodies (ADAs)
Time frame: Day 1821
Population: Immunogenicity Analysis Set: all participants who had an ADA sample both before and after the first dose of ravulizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ALXN1210 Cohort 1 | Participants Experiencing Antidrug Antibodies (ADAs) | 0 Participants |
| ALXN1210 Cohort 2 | Participants Experiencing Antidrug Antibodies (ADAs) | 0 Participants |
Secondary
Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709
Time frame: Baseline, Day 1709
Population: Pharmacodynamics (PD) Analysis Set: all participants who had a measurement both before and after the first dose of ravulizumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709 | -72.316 percent change | Standard Deviation 19.0919 |
| ALXN1210 Cohort 2 | Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709 | -97.314 percent change | Standard Deviation 3.2298 |
Secondary
Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time frame: Baseline, Day 169, Day 1821
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821 | Day 169 | -27.42 percent change | Standard Deviation 40.015 |
| ALXN1210 Cohort 1 | Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821 | Day 1821 | -12.74 percent change | Standard Deviation 54.821 |
| ALXN1210 Cohort 2 | Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821 | Day 169 | -0.49 percent change | Standard Deviation 73.116 |
| ALXN1210 Cohort 2 | Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821 | Day 1821 | 25.15 percent change | Standard Deviation 43.861 |
Secondary
Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709
Time frame: Baseline, Day 1709
Population: PD Analysis Set: all participants who had a measurement both before and after the first dose of ravulizumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709 | -99.839 percent change | Standard Deviation 0.013 |
| ALXN1210 Cohort 2 | Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709 | -99.802 percent change | Standard Deviation 0.095 |
Secondary
Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time frame: Baseline, Day 169, Day 1821
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821 | Day 169 | -22.335 percent change | Standard Deviation 42.2249 |
| ALXN1210 Cohort 1 | Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821 | Day 1821 | -35.062 percent change | Standard Deviation 30.9356 |
| ALXN1210 Cohort 2 | Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821 | Day 169 | -43.969 percent change | Standard Deviation 24.7674 |
| ALXN1210 Cohort 2 | Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821 | Day 1821 | 24.435 percent change | Standard Deviation 178.7882 |
Secondary
Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time frame: Baseline, Day 169, Day 1821
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821 | Day 169 | 40.0000 percent change | Standard Deviation 55.1362 |
| ALXN1210 Cohort 1 | Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821 | Day 1821 | 72.0000 percent change | Standard Deviation 144.81022 |
| ALXN1210 Cohort 2 | Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821 | Day 169 | 17.1429 percent change | Standard Deviation 45.35574 |
| ALXN1210 Cohort 2 | Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821 | Day 1821 | 62.5000 percent change | Standard Deviation 125 |
Secondary
Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time frame: Baseline, Day 169, Day 1933
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933 | Day 169 | 7.873 percent change | Standard Deviation 19.3064 |
| ALXN1210 Cohort 1 | Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933 | Day 1933 | 15.927 percent change | Standard Deviation 34.8796 |
| ALXN1210 Cohort 2 | Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933 | Day 169 | 25.840 percent change | Standard Deviation 62.9677 |
| ALXN1210 Cohort 2 | Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933 | Day 1933 | 13.960 percent change | Standard Deviation 78.9414 |
Secondary
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821
Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.
Time frame: Baseline, Day 169, Day 1821
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821 | Day 169 | -21.203 percent change | Standard Deviation 14.1461 |
| ALXN1210 Cohort 1 | Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821 | Day 1821 | -32.736 percent change | Standard Deviation 18.8997 |
| ALXN1210 Cohort 2 | Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821 | Day 169 | 28.784 percent change | Standard Deviation 54.2636 |
| ALXN1210 Cohort 2 | Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821 | Day 1821 | 9.763 percent change | Standard Deviation 22.5892 |
Secondary
Percent Change In Total C5 Concentration From Baseline To Day 1709
Time frame: Baseline, Day 1709
Population: PD Analysis Set: all participants who had a measurement both before and after the first dose of ravulizumab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In Total C5 Concentration From Baseline To Day 1709 | 65.852 percent change | Standard Deviation 31.2054 |
| ALXN1210 Cohort 2 | Percent Change In Total C5 Concentration From Baseline To Day 1709 | 86.676 percent change | Standard Deviation 24.6721 |
Secondary
Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141
Time frame: Day 1 and Day 141
Population: PK Analysis Set: all participants who had sufficient serum concentration data to enable the calculation of PK parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ALXN1210 Cohort 1 | Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141 | Day 1 | 2.38 h | Standard Deviation 2.404 |
| ALXN1210 Cohort 1 | Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141 | Day 141 | 4.03 h | Standard Deviation 0.035 |
| ALXN1210 Cohort 2 | Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141 | Day 1 | 1.88 h | Standard Deviation 0.957 |
| ALXN1210 Cohort 2 | Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141 | Day 141 | 2.40 h | Standard Deviation 1.124 |
Post Hoc
Percent Change In LDH Levels From Baseline To Day 1821
Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.
Time frame: Baseline, Day 1821
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ALXN1210 Cohort 1 | Percent Change In LDH Levels From Baseline To Day 1821 | -86.244 percent change | Standard Deviation 4.7348 |
| ALXN1210 Cohort 2 | Percent Change In LDH Levels From Baseline To Day 1821 | -84.413 percent change | Standard Deviation 3.6473 |