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NCT02588833: PADDOCK

Pilot Study to Assess Safety, Preliminary Efficacy and Pharmacokinetics of S.C. Pegcetacoplan (APL-2) in PNH Subjects.

Completed Phase 1 Results posted Last updated 11 January 2021
What this trial tests

Phase 1 trial testing Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria in 23 participants. Completed in 26 August 2019.

Timeline
1 December 2015
Primary endpoint
26 August 2019
26 August 2019

Quick facts

Lead sponsorApellis Pharmaceuticals, Inc.
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment23
Start date1 December 2015
Primary completion26 August 2019
Estimated completion26 August 2019
Sites7 locations across Hong Kong, New Zealand, Thailand, Malaysia

Drugs / interventions tested

Conditions studied

Sponsor

Apellis Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Paroxysmal Nocturnal Hemoglobinuria. 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.

Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Including by Severity Primary · From first dose of study drug (Day 1) up to 30 days after the last dose of study drug, up to approximately 563 days.

TEAEs were defined as adverse events (AEs) that occurred after dosing on Day 1 and up to 30 days after the last dose of study drug. A treatment-related TEAE is defined as a TEAE with a relationship to study drug of probably, possibly, unlikely, or unrelated. A serious adverse event (SAE) is defined as any AE that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant incapacity or substantial disruption of ability to conduct normal life functions; was a congenital anomaly or birth defect. TEAEs were g

All TEAEs
GroupValue95% CI
Cohort 12
Cohort 218
Treatment related TEAEs
GroupValue95% CI
Cohort 12
Cohort 29
Serious AEs
GroupValue95% CI
Cohort 11
Cohort 26
TEAEs leading to study drug discontinuation
GroupValue95% CI
Cohort 11
Cohort 22
TEAEs leading to death
GroupValue95% CI
Cohort 10
Cohort 21
TEAEs with mild intensity
GroupValue95% CI
Cohort 10
Cohort 23
TEAEs with moderate intensity
GroupValue95% CI
Cohort 12
Cohort 28
TEAEs with severe intensity
GroupValue95% CI
Cohort 10
Cohort 25
Mean Change From Baseline in Lactate Dehydrogenase (LDH) at Day 365 Primary · Baseline (Day 1) and Day 365.

Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. LDH results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 2-2105.2± 1078.79
Mean Percentage Change From Baseline in LDH at Day 365 Primary · Baseline (Day 1) and Day 365.

Serum chemistry assessments of LDH were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. LDH results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 2-84.8± 14.04
Mean Change From Baseline in Haptoglobin at Day 365 Primary · Baseline (Day 1) and Day 365.

Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Haptoglobin results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 20.066± 0.1245
Mean Percentage Change From Baseline in Haptoglobin at Day 365 Primary · Baseline (Day 1) and Day 365.

Serum chemistry assessments of haptoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Haptoglobin results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 2166.176± 311.3656
Mean Change From Baseline in Hemoglobin at Day 365 Primary · Baseline (Day 1) and Day 365.

Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Hemoglobin results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 23.68± 2.690
Mean Percentage Change From Baseline in Hemoglobin at Day 365 Primary · Baseline (Day 1) and Day 365.

Hematology assessments of hemoglobin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. Hemoglobin results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 249.86± 43.254
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 365 Secondary · Baseline (Day 1) and Day 365.

The FACIT-Fatigue Scale is a 13 item Likert scaled instrument where the subject was presented with 13 statements and asked to indicate their response as it applied to the past 7 days. The 5 possible responses were 'Not at all' (0), 'A little bit (1), 'Somewhat' (2), 'Quite a bit' (3) and 'Very much' (4). There are 13 statements with the total score ranging from 0 to 52 and higher scores indicating better quality of life. The FACIT-Fatigue Scale results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 27.1± 11.09
Mean Change From Baseline in Absolute Reticulocyte Count (ARC) at Day 365 Secondary · Baseline (Day 1) and Day 365.

Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. ARC results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 2-105.9± 70.28
Mean Percentage Change From Baseline in ARC at Day 365 Secondary · Baseline (Day 1) and Day 365.

Hematology assessments of ARC were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the different parts of the treatment period. ARC results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 2-47.5± 26.86
Mean Change From Baseline in Total Bilirubin at Day 365 Secondary · Baseline (Day 1) and Day 365.

Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the 3 parts of the treatment period. Total bilirubin results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 2-29.9± 24.34
Mean Percentage Change From Baseline in Total Bilirubin at Day 365 Secondary · Baseline (Day 1) and Day 365.

Serum chemistry assessments of total bilirubin were made at the last measurement prior to the first dose of pegcetacoplan (baseline) and periodically throughout the 3 parts of the treatment period. Total bilirubin results were summarized for Cohort 2 only.

GroupValue95% CI
Cohort 2-60.9± 19.00

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAE data is reported from first dose of study drug (Day 1) up to 30 days after the last dose of study drug, up to approximately 563 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1
Serious: 1/3 (33%)
Deaths: 0/3
Cohort 2
Serious: 6/20 (30%)
Deaths: 1/20

Serious adverse events (11 terms)

ReactionSystemCohort 1Cohort 2
HaemolysisBlood and lymphatic system disorders
HypersensitivityImmune system disorders
Abdominal neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Aplastic anaemiaBlood and lymphatic system disorders
Intravascular haemolysisBlood and lymphatic system disorders
Acute kidney injuryRenal and urinary disorders
Joint dislocationInjury, poisoning and procedural complications
PneumonitisRespiratory, thoracic and mediastinal disorders
Paroxysmal nocturnal haemoglobinuriaBlood and lymphatic system disorders
Cholecystitis acuteHepatobiliary disorders
Abdominal painGastrointestinal disorders
Other adverse events (74 terms — click to expand)

ReactionSystemCohort 1Cohort 2
Upper respiratory tract infectionInfections and infestations
Injection site erythemaGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Electrocardiogram QT prolongedInvestigations
NeutropeniaBlood and lymphatic system disorders
PharyngitisInfections and infestations
PyrexiaGeneral disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
ChromaturiaRenal and urinary disorders
HaematuriaRenal and urinary disorders
ContusionInjury, poisoning and procedural complications
DizzinessNervous system disorders
HordeolumInfections and infestations
Nasal abscessInfections and infestations
NasopharyngitisInfections and infestations
Ophthalmic herpes zosterInfections and infestations
ParonychiaInfections and infestations
Urinary tract infectionInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Productive coughRespiratory, thoracic and mediastinal disorders
RhinorrhoeaRespiratory, thoracic and mediastinal disorders
Injection site indurationGeneral disorders
Injection site painGeneral disorders
Injection site swellingGeneral disorders
Oedema peripheralGeneral disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Gingival bleedingGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
VomitingGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations

Most-reported serious reactions: Haemolysis, Hypersensitivity, Abdominal neoplasm, Aplastic anaemia, Intravascular haemolysis, Acute kidney injury, Joint dislocation, Pneumonitis.

Data from ClinicalTrials.gov NCT02588833 adverse events section.

Sponsor's own description

The objectives of the study are to assess the safety, tolerability, preliminary efficacy and PK of multiple subcutaneous (SC) doses of pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who have not received treatment with eculizumab in the past. An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC doses of pegcetacoplan when administered to PNH patients.

Publications & conference data

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

  1. New insights into the immune functions of complement.
    Reis ES, Mastellos DC, Hajishengallis G, Lambris JD. · · 2019 · cited 357× · PMID 31048789 · DOI 10.1038/s41577-019-0168-x
  2. The renaissance of complement therapeutics.
    Ricklin D, Mastellos DC, Reis ES, Lambris JD. · · 2018 · cited 305× · PMID 29199277 · DOI 10.1038/nrneph.2017.156
  3. 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
  4. Diseases of complement dysregulation-an overview.
    Wong EKS, Kavanagh D. · · 2018 · cited 80× · PMID 29327071 · DOI 10.1007/s00281-017-0663-8
  5. C3 inhibition with pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria treated with eculizumab.
    de Castro C, Grossi F, Weitz IC, Maciejewski J, et al · · 2020 · cited 76× · PMID 33464651 · DOI 10.1002/ajh.25960
  6. New milestones ahead in complement-targeted therapy.
    Ricklin D, Lambris JD. · · 2016 · cited 73× · PMID 27321574 · DOI 10.1016/j.smim.2016.06.001
  7. Pegcetacoplan controls hemolysis in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria.
    Wong RSM, Navarro-Cabrera JR, Comia NS, Goh YT, et al · · 2023 · cited 50× · PMID 36848639 · DOI 10.1182/bloodadvances.2022009129
  8. 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

Verify or expand the search:

Other trials of Pegcetacoplan

Trials testing the same drug.

Other recruiting trials for Paroxysmal Nocturnal Hemoglobinuria

Currently open trials in the same condition.

Other Apellis Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02588833.

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