Phase 3
N=80
Study to Evaluate the Efficacy and Safety of APL-2 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal Nocturnal Hemoglobinuria
Bottom Line
View on ClinicalTrials.gov: NCT03500549 ↗Enrolled (actual)
80
Serious AEs
14.4%
Results posted
Mar 2022
Primary outcome: Primary: Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP — 2.37; -1.47 Grams per deciliter (g/dL) — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Pegcetacoplan (Drug); Soliris (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Apellis Pharmaceuticals, Inc.
- Primary completion
- Nov 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Least Squares (LS) Mean Change From Baseline to Week 16 in Hemoglobin (Hb) Level During the RCP |
2.37; -1.47 | <0.0001 sig |
| SECONDARY Percentage of Subjects Who Did Not Require a Transfusion (Transfusion Avoidance) During the RCP |
85.4; 15.4 | <0.0001 sig |
| SECONDARY LS Mean Change From Baseline to Week 16 in Absolute Reticulocyte Count (ARC) During the RCP |
-135.82; 27.79 | <0.0001 sig |
| SECONDARY LS Mean Change From Baseline to Week 16 in Lactate Dehydrogenase (LDH) Level During the RCP |
-14.76; -10.12 | 0.9557 |
| SECONDARY LS Mean Change From Baseline to Week 16 in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score During the RCP |
9.22; -2.65 | 0.0005 sig |
| SECONDARY Percentage of Subjects Who Achieved a Hb Response in the Absence of Transfusions at Week 16 |
75.6; 0.0 | — |
| SECONDARY Percentage of Subjects Who Achieved Reticulocyte Normalization in the Absence of Transfusions at Week 16 |
78.0; 2.6 | — |
| SECONDARY Percentage of Subjects Who Achieved Hb Normalization in the Absence of Transfusions at Week 16 |
34.1; 0.0 | — |
| SECONDARY LS Mean Change From Baseline to Week 16 in Indirect Bilirubin Level During the RCP |
-17.78; 4.15 | 0.0002 sig |
| SECONDARY LS Mean Change From Baseline to Week 16 in Haptoglobin Level During the RCP |
-0.02; 0.12 | 0.0369 sig |
| SECONDARY LS Mean Change From Baseline to Week 16 in Linear Analog Scale Assessment (LASA) Scores During the RCP |
49.38; -9.72 | 0.0069 sig |
| SECONDARY LS Mean Change From Baseline to Week 16 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 Scale (QLQ-C30) Scores During the RCP |
15.91; -2.71; 16.92; 4.06; 15.39; -9.04 | 0.0486 sig |
| SECONDARY Total Number of PRBC Units Transfused During the RCP |
26; 198 | <0.0001 sig |
| SECONDARY Mean Change From Baseline to Week 48 in Hb Level During the Treatment Period |
2.47; 2.93 | — |
| SECONDARY Mean Change From Week 17 to Week 48 in Hb Level During the Open-label Period |
-0.16; 2.89 | — |
| SECONDARY Mean Change From Baseline to Week 48 in ARC During the Treatment Period |
-135.64; -128.22 | — |
| SECONDARY Mean Change From Week 17 to Week 48 in ARC During the Open-label Period |
-6.50; -121.15 | — |
| SECONDARY Mean Change From Baseline to Week 48 in LDH Level During the Treatment Period |
-41.53; -105.27 | — |
| SECONDARY Mean Change From Week 17 to Week 48 in LDH Level During the Open-label Period |
8.03; -46.84 | — |
| SECONDARY Mean Change From Baseline to Week 48 in FACIT-Fatigue Scale Score During the Treatment Period |
10.14; 9.62 | — |
| SECONDARY Mean Change From Week 17 to Week 48 in FACIT-Fatigue Scale Score During the Open-label Period |
1.28; 10.19 | — |
| SECONDARY Mean Change From Baseline to Week 48 in LASA Scores During the Treatment Period |
58.66; 56.52 | — |
| SECONDARY Mean Change From Week 17 to Week 48 in LASA Scores During the Open-label Period |
13.13; 62.92 | — |
| SECONDARY Mean Change From Baseline to Week 48 in QLQ-C30 Scores During the Treatment Period |
18.89; 13.99; 15.33; 10.80; 16.67; 20.11 | — |
| SECONDARY Mean Change From Week 17 to Week 48 in QLQ-C30 Scores During the Open-label Period |
7.22; 23.08; 0.89; 11.03; 5.00; 19.87 | — |
| SECONDARY Total Number of PRBC Units Transfused During the Open-Label Period |
68; 110; 14 | — |
Summary
Evaluation of the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglobinuria
Eligibility 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 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)
Data sourced from ClinicalTrials.gov (NCT03500549). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.