Phase IIa study of APL-2 in patients with PNH

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2017-005140-16-GR
• Date of registration: 02/04/2018
• Prospective Registration: Yes
• Primary sponsor: Apellis Pharmaceuticals
• Public title: Phase IIa study of APL-2 in patients with PNH
• Scientific title: A Phase IIa, Open Label, Multiple Dose Study to Assess the Safety, Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects with Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Date of first enrolment: 04/05/2018
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-005140-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Greece, Poland, Romania, Serbia

Contacts

• Name: Head of Clinical Operations
• Affiliation: Apellis Pharmaceuticals

• Name: Head of Clinical Operations
• Affiliation: Apellis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion criteria:
1. At least 18 years old (inclusive)
2. Diagnosed with PNH (WBC clone >10%)
3. Lactose dehydrogenase =2 times the upper limit of normal
4. Screening Ferritin = normal and Total Iron Binding Capacity (TIBC) = LLN based on central lab reference ranges. If a subject is receiving iron supplements at screening, the investigator must ensure that his/her dose has been stable for 8 weeks prior to enrolment and must be maintained throughout the study (see Protocol Section 8.4.4)
5. Last transfusion within 12 months prior to screening
6. Platelet count of >30,000/mm3 at the screening visit
7. Absolute neutrophil count >500/ mm3 at the screening visit
8. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening and must agree to use protocol defined methods of contraception for the duration of the study
9. Males must agree to use protocol defined methods of contraception and agree to refrain from donating sperm for the duration of the study
10. 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
11. Willing and able to give informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
1. Prior eculizumab (Soliris®) treatment
2. Active bacterial infection
3. Hereditary complement deficiency
4. History of bone marrow transplantation
5. Concurrent SAA, defined as currently receiving immunosuppressive therapy for SAA including but not limited to cyclosporin A, tacrolimus, mycophenolate mofetil or antithymocyte globulin
6. Participation in any other investigational drug trial or exposure to other investigational agent, device or procedure within 30 days
7. Evidence of QTcF prolongation defined as >450 ms for males and >470 ms for females at screening
8. Breast-feeding women
9. History of meningococcal disease


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Paroxysmal Nocturnal Hemoglobinuria (PNH)
MedDRA version: 20.1 Level: LLT Classification code 10055629 Term: Paroxysmal nocturnal hemoglobinuria System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Code: APL-2
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Not yet assigned
CAS Number: 2019171-69-6
Current Sponsor code: APL-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Primary Outcome(s)

Primary end point(s): Primary Safety Endpoint:
The primary safety endpoints of the study are the number and severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2.

Primary Efficacy Endpoints:
• Change from baseline in Lactate dehydrogenase (LD)
• Change from baseline in Haptoglobin
• Change from baseline in Hemoglobin (Hb)

Timepoint(s) of evaluation of this end point: Primary Safety Endpoint:
after dosing on Day 1 and up to 30 days after the last dose of study medication.
Primary Efficacy Endpoints:
Change from baseline in LD, Haptoglobin and Hb: will be calculated for each post dose assessment. The baseline: the last measurement prior to the start of dosing. Please refer to STUDY FLOW CHART in the Protocol.

Main Objective: The objectives of the study are to assess safety, tolerability, preliminary efficacy and PK of multiple SC doses of APL-2 in subjects with paroxysmal nocturnal hemoglobinuria (PNH) who have not received treatment with eculizumab (Soliris)® in the past.

Secondary Objective: An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC doses of APL-2 when administered to PNH subjects.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: • APL-2 plasma concentrations (and PK parameters): Plasma concentrations of APL-2 will be determined from multiple samples taken between Day 1 and the Exit Visit.
• Change from baseline in FACIT Fatigue Scale score: Please refer to STUDY FLOW CHART in the Protocol
• Change from baseline in reticulocyte count: Please refer to STUDY FLOW CHART in the Protocol
• Change from baseline in total bilirubin: Please refer to STUDY FLOW CHART in the Protocol
• Number of RBC transfusions per month: Please refer to STUDY FLOW CHART in the Protocol
• Change from baseline in Linear Analog Scale Assessment for Quality of Life: Please refer to STUDY FLOW CHART in the Protocol
Baseline: the last measurement prior to the start of dosing.
Baseline for transfusions: from the 12 M transfusion history

Secondary end point(s): • APL-2 plasma concentrations (and pharmacokinetic (PK) parameters as appropriate)
• Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale score
• Change from baseline in reticulocyte count
• Change from baseline in total bilirubin
• Number of red blood cell (RBC) transfusions per month
• Change from baseline in Linear Analog Scale Assessment (LASA) for Quality of Life
Baseline will be taken as the last measurement prior to the start of dosing.
For transfusions baseline will be taken from the 12 month transfusion history.

Exploratory PD markers include:
• Complement (CH50, AP50, and C3) levels
• C3 deposition on RBC cells
• Clonal distribution of PNH RBCs

Secondary ID(s)

2017-005140-16-BG

APL2-202

Source(s) of Monetary Support

Apellis Pharmaceuticals

Ethics review

Status: Approved
Approval date:
Contact: