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NCT02264639

A Phase I Study to Assess the Safety of Pegcetacoplan (APL-2) as an Add-On to Standard of Care in Subjects With PNH

Completed Phase 1 Results posted Last updated 8 January 2021
What this trial tests

Phase 1 trial testing Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria (PNH) in 9 participants. Completed in 22 October 2018.

Timeline
23 February 2015
Primary endpoint
22 October 2018
22 October 2018

Quick facts

Lead sponsorApellis Pharmaceuticals, Inc.
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment9
Start date23 February 2015
Primary completion22 October 2018
Estimated completion22 October 2018
Sites7 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Apellis Pharmaceuticals, Inc. — full company profile →

Who can join

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

Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase Primary · From single dose of study drug (Day 1) up to 30 days

TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.

Any TEAE
GroupValue95% CI
Cohort 1 Single-dose Phase1
Cohort 2 Single-dose Phase2
TEAE at least possibly related to study drug
GroupValue95% CI
Cohort 1 Single-dose Phase0
Cohort 2 Single-dose Phase1
Serious TEAE
GroupValue95% CI
Cohort 1 Single-dose Phase0
Cohort 2 Single-dose Phase0
TEAE leading to study drug discontinuation
GroupValue95% CI
Cohort 1 Single-dose Phase0
Cohort 2 Single-dose Phase0
TEAE leading to death
GroupValue95% CI
Cohort 1 Single-dose Phase0
Cohort 2 Single-dose Phase0
Maximum severity of all TEAEs: mild
GroupValue95% CI
Cohort 1 Single-dose Phase0
Cohort 2 Single-dose Phase1
Maximum severity of all TEAEs: moderate
GroupValue95% CI
Cohort 1 Single-dose Phase1
Cohort 2 Single-dose Phase1
Maximum severity of all TEAEs: severe
GroupValue95% CI
Cohort 1 Single-dose Phase0
Cohort 2 Single-dose Phase0
Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase Primary · From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).

TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.

Any TEAE
GroupValue95% CI
Cohort 1 Multiple-dose Phase1
Cohort 2 Multiple-dose Phase2
Cohort 3 Multiple-dose Phase1
Cohort 4 Multiple-dose Phase6
TEAE at least possibly related to study drug
GroupValue95% CI
Cohort 1 Multiple-dose Phase0
Cohort 2 Multiple-dose Phase1
Cohort 3 Multiple-dose Phase1
Cohort 4 Multiple-dose Phase4
Serious TEAE
GroupValue95% CI
Cohort 1 Multiple-dose Phase0
Cohort 2 Multiple-dose Phase0
Cohort 3 Multiple-dose Phase0
Cohort 4 Multiple-dose Phase2
TEAE leading to study drug discontinuation
GroupValue95% CI
Cohort 1 Multiple-dose Phase1
Cohort 2 Multiple-dose Phase0
Cohort 3 Multiple-dose Phase0
Cohort 4 Multiple-dose Phase0
TEAE leading to death
GroupValue95% CI
Cohort 1 Multiple-dose Phase0
Cohort 2 Multiple-dose Phase0
Cohort 3 Multiple-dose Phase0
Cohort 4 Multiple-dose Phase0
Maximum severity of all TEAEs: mild
GroupValue95% CI
Cohort 1 Multiple-dose Phase0
Cohort 2 Multiple-dose Phase0
Cohort 3 Multiple-dose Phase1
Cohort 4 Multiple-dose Phase0
Maximum severity of all TEAEs: moderate
GroupValue95% CI
Cohort 1 Multiple-dose Phase0
Cohort 2 Multiple-dose Phase2
Cohort 3 Multiple-dose Phase0
Cohort 4 Multiple-dose Phase2
Maximum severity of all TEAEs: severe
GroupValue95% CI
Cohort 1 Multiple-dose Phase1
Cohort 2 Multiple-dose Phase0
Cohort 3 Multiple-dose Phase0
Cohort 4 Multiple-dose Phase4
Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4 Primary · Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.

Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.

GroupValue95% CI
Cohort 4 Multiple-dose Phase6,500,000± 3,990,000
Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4 Primary · Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.

Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.

270 mg Dose
GroupValue95% CI
Cohort 4 Multiple-dose Phase627± 207
360 mg Dose
GroupValue95% CI
Cohort 4 Multiple-dose Phase543± 192
440 mg Dose
GroupValue95% CI
Cohort 4 Multiple-dose Phase624± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: TEAE data is reported from first dose of study drug up to 30 days after last dose of study drug (Cohorts 1 and 2, single-dose phase: up to 30 days; Cohorts 1-3, multiple-dose phase: up to 58 days; Cohort 4, multiple-dose phase: up to 759 days).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 Single-dose Phase
Serious: 0/2 (0%)
Deaths: 1/2
Cohort 2 Single-dose Phase
Serious: 0/2 (0%)
Deaths: 0/2
Cohort 1 Multiple-dose Phase
Serious: 0/1 (0%)
Deaths: 0/1
Cohort 2 Multiple-dose Phase
Serious: 0/2 (0%)
Deaths: 0/2
Cohort 3 Multiple-dose Phase
Serious: 0/2 (0%)
Deaths: 0/2
Cohort 4 Multiple-dose Phase
Serious: 2/6 (33%)
Deaths: 0/6

Serious adverse events (7 terms)

ReactionSystemCohort 1 Single-dose PhaseCohort 2 Single-dose PhaseCohort 1 Multiple-dose PhaseCohort 2 Multiple-dose PhaseCohort 3 Multiple-dose PhaseCohort 4 Multiple-dose Phase
AnaemiaBlood and lymphatic system disorders
Lower gastrointestinal haemorrhageGastrointestinal disorders
PancreatitisGastrointestinal disorders
Portal vein thrombosisHepatobiliary disorders
SepsisInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Other adverse events (106 terms — click to expand)

ReactionSystemCohort 1 Single-dose PhaseCohort 2 Single-dose PhaseCohort 1 Multiple-dose PhaseCohort 2 Multiple-dose PhaseCohort 3 Multiple-dose PhaseCohort 4 Multiple-dose Phase
HeadacheNervous system disorders
Injection-site bruisingGeneral disorders
Injection-site painGeneral disorders
Injection-site erythemaGeneral disorders
PyrexiaGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Upper respiratory tract infectionInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
Injection-site indurationGeneral disorders
Injection-site swellingGeneral disorders
PruritusSkin and subcutaneous tissue disorders
PetechiaeSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
ErythemaSkin and subcutaneous tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Aspartate aminotransferase increasedInvestigations
Activated partial thromboplastin time prolongedInvestigations
InfluenzaInfections and infestations
Nasal congestionRespiratory, thoracic and mediastinal disorders
Vision blurredEye disorders
ContusionInjury, poisoning and procedural complications
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Oedema peripheralGeneral disorders
Urinary tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Serum ferritin increasedInvestigations
Memory impairmentNervous system disorders
Night sweatsSkin and subcutaneous tissue disorders
Injection-site pruritusGeneral disorders
Infusion-site bruisingGeneral disorders
Injection-site haemorrhageGeneral disorders
AstheniaGeneral disorders
ChillsGeneral disorders

Most-reported serious reactions: Anaemia, Lower gastrointestinal haemorrhage, Pancreatitis, Portal vein thrombosis, Sepsis, Alanine aminotransferase increased, Aspartate aminotransferase increased.

Data from ClinicalTrials.gov NCT02264639 adverse events section.

Sponsor's own description

This study will be the initial exploration of pegcetacoplan in patients with PNH. The assessments of the safety, tolerability, PK, and PD following administration of single and multiples doses of pegcetacoplan will guide decisions to further develop the drug.

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. Complement, a target for therapy in inflammatory and degenerative diseases.
    Morgan BP, Harris CL. · · 2015 · cited 346× · PMID 26493766 · DOI 10.1038/nrd4657
  3. The renaissance of complement therapeutics.
    Ricklin D, Mastellos DC, Reis ES, Lambris JD. · · 2018 · cited 305× · PMID 29199277 · DOI 10.1038/nrneph.2017.156
  4. 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
  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. Applying complement therapeutics to rare diseases.
    Reis ES, Mastellos DC, Yancopoulou D, Risitano AM, et al · · 2015 · cited 51× · PMID 26341313 · DOI 10.1016/j.clim.2015.08.009
  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 (PNH)

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/NCT02264639.

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