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NCT02598583

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

Completed Phase 1, PHASE2 Results posted Last updated 16 May 2022
What this trial tests

Phase 1, PHASE2 trial testing ALXN1210 in PNH in 13 participants. Completed in 11 March 2021.

Timeline
12 November 2015
Primary endpoint
14 July 2016
11 March 2021

Quick facts

Lead sponsorAlexion Pharmaceuticals, Inc.
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment13
Start date12 November 2015
Primary completion14 July 2016
Estimated completion11 March 2021
Sites8 locations across Australia, South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Alexion Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with PNH. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169 Primary · Baseline, Day 169

Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.

GroupValue95% CI
ALXN1210 Cohort 1-85.952± 3.1897
ALXN1210 Cohort 2-84.736± 3.7736
Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821 Secondary · Baseline, Day 169, Day 1821

Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

Day 169
GroupValue95% CI
ALXN1210 Cohort 1-22.335± 42.2249
ALXN1210 Cohort 2-43.969± 24.7674
Day 1821
GroupValue95% CI
ALXN1210 Cohort 1-35.062± 30.9356
ALXN1210 Cohort 224.435± 178.7882
Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821 Secondary · Baseline, Day 169, Day 1821

Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

Day 169
GroupValue95% CI
ALXN1210 Cohort 140.0000± 55.13620
ALXN1210 Cohort 217.1429± 45.35574
Day 1821
GroupValue95% CI
ALXN1210 Cohort 172.0000± 144.81022
ALXN1210 Cohort 262.5000± 125.00000
Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821 Secondary · Baseline, Day 169, Day 1821

Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

Day 169
GroupValue95% CI
ALXN1210 Cohort 1-21.203± 14.1461
ALXN1210 Cohort 228.784± 54.2636
Day 1821
GroupValue95% CI
ALXN1210 Cohort 1-32.736± 18.8997
ALXN1210 Cohort 29.763± 22.5892
Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933 Secondary · Baseline, Day 169, Day 1933

Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

Day 169
GroupValue95% CI
ALXN1210 Cohort 17.873± 19.3064
ALXN1210 Cohort 225.840± 62.9677
Day 1933
GroupValue95% CI
ALXN1210 Cohort 115.927± 34.8796
ALXN1210 Cohort 213.960± 78.9414
Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821 Secondary · Baseline, Day 169, Day 1821

Baseline was defined as the last non-missing assessment value prior to the first ALXN1210 infusion.

Day 169
GroupValue95% CI
ALXN1210 Cohort 1-27.42± 40.015
ALXN1210 Cohort 2-0.49± 73.116
Day 1821
GroupValue95% CI
ALXN1210 Cohort 1-12.74± 54.821
ALXN1210 Cohort 225.15± 43.861
Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821 Secondary · 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.

Fatigue: Day 169
GroupValue95% CI
ALXN1210 Cohort 11
ALXN1210 Cohort 21
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 15
ALXN1210 Cohort 26
Fatigue: Day 1821
GroupValue95% CI
ALXN1210 Cohort 12
ALXN1210 Cohort 21
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 13
ALXN1210 Cohort 23
Abdominal pain: Day 169
GroupValue95% CI
ALXN1210 Cohort 10
ALXN1210 Cohort 23
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 16
ALXN1210 Cohort 24
Abdominal pain: Day 1821
GroupValue95% CI
ALXN1210 Cohort 10
ALXN1210 Cohort 22
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 15
ALXN1210 Cohort 22
Dyspnoea: Day 169
GroupValue95% CI
ALXN1210 Cohort 12
ALXN1210 Cohort 21
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 14
ALXN1210 Cohort 26
Dyspnoea: Day 1821
GroupValue95% CI
ALXN1210 Cohort 12
ALXN1210 Cohort 21
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 13
ALXN1210 Cohort 23
Dysphagia: Day 169
GroupValue95% CI
ALXN1210 Cohort 10
ALXN1210 Cohort 21
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 16
ALXN1210 Cohort 26
Dysphagia: Day 1821
GroupValue95% CI
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 10
ALXN1210 Cohort 20
ALXN1210 Cohort 15
ALXN1210 Cohort 24
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1 Secondary · Day 1

AUCt reported in hours\*microgram/milliliter (h\*ug/mL).

GroupValue95% CI
ALXN1210 Cohort 114273.95± 4907.438
ALXN1210 Cohort 242366.62± 3710.120
AUCt/ Dose-normalized (D) At Day 1 Secondary · Day 1
GroupValue95% CI
ALXN1210 Cohort 135.68± 12.269
ALXN1210 Cohort 270.61± 6.184
Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141 Secondary · Day 141
GroupValue95% CI
ALXN1210 Cohort 1216515.22± 68099.982
ALXN1210 Cohort 2217936.47± 31023.979
AUCtau/D At Day 141 Secondary · Day 141
GroupValue95% CI
ALXN1210 Cohort 1240.57± 75.667
ALXN1210 Cohort 2242.15± 34.471
Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141 Secondary · Day 1 and Day 141
Day 1
GroupValue95% CI
ALXN1210 Cohort 1114.00± 15.556
ALXN1210 Cohort 2203.50± 10.279
Day 141
GroupValue95% CI
ALXN1210 Cohort 1514.00± 147.078
ALXN1210 Cohort 2512.25± 64.958

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 through Day 1957. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

ALXN1210 Cohort 1
Serious: 3/6 (50%)
Deaths: 0/6
ALXN1210 Cohort 2
Serious: 4/7 (57%)
Deaths: 0/7

Serious adverse events (10 terms)

ReactionSystemALXN1210 Cohort 1ALXN1210 Cohort 2
AnaemiaBlood and lymphatic system disorders——
Meningococcal infectionInfections and infestations——
Parvovirus infectionInfections and infestations——
PneumoniaInfections and infestations——
Tubo-ovarian abscessInfections and infestations——
Bile duct stoneHepatobiliary disorders——
CholangitisHepatobiliary disorders——
Cholangitis acuteHepatobiliary disorders——
Cholecystitis acuteHepatobiliary disorders——
ContusionInjury, poisoning and procedural complications——
Other adverse events (97 terms — click to expand)

ReactionSystemALXN1210 Cohort 1ALXN1210 Cohort 2
Upper respiratory tract infectionInfections and infestations——
HeadacheNervous system disorders——
Abdominal painGastrointestinal disorders——
ConstipationGastrointestinal disorders——
PyrexiaGeneral disorders——
DizzinessNervous system disorders——
HordeolumInfections and infestations——
NasopharyngitisInfections and infestations——
LaryngitisInfections and infestations——
PharyngitisInfections and infestations——
DyspepsiaGastrointestinal disorders——
EnterocolitisGastrointestinal disorders——
ToothacheGastrointestinal disorders——
FatigueGeneral disorders——
Back painMusculoskeletal and connective tissue disorders——
CoughRespiratory, thoracic and mediastinal disorders——
AnaemiaBlood and lymphatic system disorders——
Hot flushVascular disorders——
InfluenzaInfections and infestations——
DiarrhoeaGastrointestinal disorders——
Gastrooesophageal reflux diseaseGastrointestinal disorders——
InsomniaPsychiatric disorders——
Neuropathy peripheralNervous system disorders——
PresyncopeNervous system disorders——
Viral upper respiratory tract infectionInfections and infestations——
NauseaGastrointestinal disorders——
VomitingGastrointestinal disorders——
Oedema peripheralGeneral disorders——
PainGeneral disorders——
Bone painMusculoskeletal and connective tissue disorders——
Joint range of motion decreasedMusculoskeletal and connective tissue disorders——
DyspnoeaRespiratory, thoracic and mediastinal disorders——
Reflux laryngitisRespiratory, thoracic and mediastinal disorders——
Blood bilirubin increasedInvestigations——
Blood creatinine increasedInvestigations——
Neutrophil count decreasedInvestigations——
Decreased appetiteMetabolism and nutrition disorders——
Atrial flutterCardiac disorders——
SyncopeNervous system disorders——
Urinary tract infectionInfections and infestations——

Most-reported serious reactions: Anaemia, Meningococcal infection, Parvovirus infection, Pneumonia, Tubo-ovarian abscess, Bile duct stone, Cholangitis, Cholangitis acute.

Data from ClinicalTrials.gov NCT02598583 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The renaissance of complement therapeutics.
    Ricklin D, Mastellos DC, Reis ES, Lambris JD. · · 2018 · cited 305× · PMID 29199277 · DOI 10.1038/nrneph.2017.156
  2. Anti-complement Treatment for Paroxysmal Nocturnal Hemoglobinuria: Time for Proximal Complement Inhibition? A Position Paper From the SAAWP of the EBMT.
    Risitano AM, Marotta S, Ricci P, Marano L, et al · · 2019 · cited 155× · PMID 31258525 · DOI 10.3389/fimmu.2019.01157
  3. New milestones ahead in complement-targeted therapy.
    Ricklin D, Lambris JD. · · 2016 · cited 73× · PMID 27321574 · DOI 10.1016/j.smim.2016.06.001
  4. Ravulizumab (ALXN1210) in patients with paroxysmal nocturnal hemoglobinuria: results of 2 phase 1b/2 studies.
    Röth A, Rottinghaus ST, Hill A, Bachman ES, et al · · 2018 · cited 65× · PMID 30171081 · DOI 10.1182/bloodadvances.2018020644
  5. How we('ll) treat paroxysmal nocturnal haemoglobinuria: diving into the future.
    Risitano AM, Peffault de Latour R. · · 2022 · cited 48× · PMID 34355382 · DOI 10.1111/bjh.17753
  6. Treatment of Rare Inflammatory Kidney Diseases: Drugs Targeting the Terminal Complement Pathway.
    Anliker-Ort M, Dingemanse J, van den Anker J, Kaufmann P. · · 2020 · cited 33× · PMID 33362783 · DOI 10.3389/fimmu.2020.599417
  7. Complement System in Cutaneous Squamous Cell Carcinoma.
    Riihilä P, Nissinen L, Knuutila J, Rahmati Nezhad P, et al · · 2019 · cited 29× · PMID 31331124 · DOI 10.3390/ijms20143550
  8. Current Opinions on the Clinical Utility of Ravulizumab for the Treatment of Paroxysmal Nocturnal Hemoglobinuria.
    Gurnari C, Nautiyal I, Pagliuca S. · · 2021 · cited 5× · PMID 34934322 · DOI 10.2147/tcrm.s273360

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Other trials of ALXN1210

Trials testing the same drug.

Other recruiting trials for PNH

Currently open trials in the same condition.

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Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing