Working… Menu

Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03500549
Recruitment Status : Completed
First Posted : April 18, 2018
Last Update Posted : December 8, 2020
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Brief Summary:
Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria

Condition or disease Intervention/treatment Phase
Paroxysmal Nocturnal Hemoglobinuria Drug: APL-2 Drug: Soliris Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Multi-Center, Open-Label, Active-Comparator Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Actual Study Start Date : June 14, 2018
Actual Primary Completion Date : November 14, 2019
Actual Study Completion Date : August 13, 2020

Arm Intervention/treatment
Experimental: 1,080mg APL-2 administered subcutaneously
1,080mg APL-2 administered subcutaneously twice weekly or every three days.
Drug: APL-2
Complement (C3) Inhibitor

Active Comparator: Eculizumab
Complement (C5) Inhibitor
Drug: APL-2
Complement (C3) Inhibitor

Drug: Soliris
Complement (C5) Inhibitor

Primary Outcome Measures :
  1. Hemoglobin [ Time Frame: 16 weeks ]
    Week 16 change from baseline in hemoglobin level

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • At least 18 years of age
  • Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
  • On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
  • Hb <10.5 g/dL at the Screening Visit
  • Absolute reticulocyte count > 1.0x ULN at the Screening Visit
  • Platelet count of >50,000/mm3 at the Screening Visit
  • Absolute neutrophil count >500/mm3 at the Screening Visit
  • Vaccination against Neisseria meningitides types A, C, W, Y and B, Streptococcus pneumoniae and Haemophilus influenzae Type B (Hib) either within 2 years prior to Day 1 dosing, or within 14 days after starting treatment with APL-2. Unless documented evidence exists that subjects are non-responders to vaccination as evidenced by titers or display titer levels within acceptable local limits
  • Women of child-bearing potential (WOCBP) must have a negative pregnancy test at the Screening and Day -28 Visit (Run-in Period) and must agree to use protocol defined methods of contraception for the duration of the study and 90 days after their last dose of study drug
  • Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study and 90 days after their last dose of study drug
  • Willing and able to give informed consent
  • Willing and able to self-administer APL-2 (administration by caregiver will be allowed)
  • Have a body mass index (BMI) ≤35.0 kg/m2

Exclusion Criteria:

  • Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2)
  • Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
  • Hereditary complement deficiency
  • History of bone marrow transplantation
  • History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
  • Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
  • Currently breast-feeding women
  • Inability to cooperate or any condition that, in the opinion of the investigator, could increase the subject's risk of participating in the study or confound the outcome of the study

This study includes cardiac safety evaluations. The following cardiac eligibility criteria are necessary to avoid confounding the cardiac safety outcomes:

  • History or family history of Long QT Syndrome or torsade de pointes, unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden death
  • Myocardial infarction, CABG, coronary or cerebral artery stenting and /or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months or greater than Class 2 Angina Pectoris or NYHA Heart Failure Class >2
  • QTcF > 470 ms, PR > 280 ms
  • Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block unless the patient has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities
  • Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening
  • Receiving any other QTc-prolonging drugs (see Appendix 4 in Section 19.4), at a stable dose for less than 3 weeks prior to dosing
  • Receiving prophylactic ciprofloxacin, erythromycin or azithromycin for less than one week prior to the first dose of study medication (must have a repeat screening ECG after one week of prophylactic antibiotics with QTcF < 470 ms)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03500549

Show Show 53 study locations
Sponsors and Collaborators
Apellis Pharmaceuticals, Inc.
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Apellis Pharmaceuticals, Inc. Identifier: NCT03500549    
Other Study ID Numbers: APL2-302
First Posted: April 18, 2018    Key Record Dates
Last Update Posted: December 8, 2020
Last Verified: December 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Hemoglobinuria, Paroxysmal
Urination Disorders
Urologic Diseases
Urological Manifestations
Anemia, Hemolytic
Hematologic Diseases
Myelodysplastic Syndromes
Bone Marrow Diseases