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Study to Evaluate the Efficacy and Safety of APL-2 in Patients With 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03500549
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : May 16, 2019
Information provided by (Responsible Party):
Apellis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE April 10, 2018
First Posted Date  ICMJE April 17, 2018
Last Update Posted Date May 16, 2019
Actual Study Start Date  ICMJE June 14, 2018
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 10, 2018)
Hemoglobin [ Time Frame: 16 weeks ]
Week 16 change from baseline in hemoglobin level
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03500549 on Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Efficacy and Safety of APL-2 in Patients With PNH
Official Title  ICMJE 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)
Brief Summary Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Paroxysmal Nocturnal Hemoglobinuria
Intervention  ICMJE
  • Drug: APL-2
    Complement (C3) Inhibitor
  • Drug: Soliris
    Complement (C5) Inhibitor
Study Arms  ICMJE
  • Experimental: 1,080mg APL-2 administered subcutaneously
    1,080mg APL-2 administered subcutaneously twice weekly or every three days.
    Intervention: Drug: APL-2
  • Active Comparator: Eculizumab
    Complement (C5) Inhibitor
    • Drug: APL-2
    • Drug: Soliris
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 10, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. At least 18 years of age
  2. Primary diagnosis of PNH confirmed by high-sensitivity flow cytometry
  3. On treatment with eculizumab. Dose of eculizumab must have been stable for at least 3 months prior to the Screening Visit
  4. Hb <10.5 g/dL at the Screening Visit
  5. Absolute reticulocyte count > 1.0x ULN at the Screening Visit
  6. Platelet count of >50,000/mm3 at the Screening Visit
  7. Absolute neutrophil count >500/mm3 at the Screening Visit
  8. 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
  9. 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
  10. 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
  11. Willing and able to give informed consent
  12. Willing and able to self-administer APL-2 (administration by caregiver will be allowed)
  13. Have a body mass index (BMI) ≤35.0 kg/m2

Exclusion Criteria:

  1. Active bacterial infection that has not resolved within 14 week of Day -28 (first dose of APL-2)
  2. Receiving iron, folic acid, vitamin B12 and EPO, unless the dose is stable, in the 4 weeks prior to Screening
  3. Hereditary complement deficiency
  4. History of bone marrow transplantation
  5. History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration
  6. Participation in any other investigational drug trial or exposure to other investigational agent within 30 days or 5 half-lives (whichever is longer)
  7. Currently breast-feeding women
  8. 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:

  9. 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
  10. 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
  11. QTcF > 470 ms, PR > 280 ms
  12. 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
  13. Receiving Class 1 or Class 3 antiarrhythmic agents, or arsenic, methadone, ondansetron or pentamidine at screening
  14. 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
  15. 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Allen Papazian 617-977-5700
Listed Location Countries  ICMJE Australia,   Canada,   Germany,   Japan,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03500549
Other Study ID Numbers  ICMJE APL2-302
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Apellis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Apellis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Apellis Pharmaceuticals, Inc.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP