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

• Register: ClinicalTrials.gov
• Last refreshed on: 11 January 2021
• Main ID: NCT03500549
• Date of registration: 10/04/2018
• Prospective Registration: Yes
• Primary sponsor: Apellis Pharmaceuticals, Inc.
• Public title: Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Scientific 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)
• Date of first enrolment: June 14, 2018
• Target sample size: 80
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03500549
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Japan, Korea, Republic of, Russian Federation, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

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)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Paroxysmal Nocturnal Hemoglobinuria

Intervention(s)

Drug: APL-2

Drug: Soliris

Primary Outcome(s)

Hemoglobin [Time Frame: 16 weeks]

Secondary ID(s)

APL2-302

Source(s) of Monetary Support

Please refer to primary and secondary sponsors