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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02588833




Registration number
NCT02588833
Ethics application status
Date submitted
27/10/2015
Date registered
28/10/2015
Date last updated
7/02/2020

Titles & IDs
Public title
Pilot Study to Assess Safety, Preliminary Efficacy and Pharmacokinetics of S.C. APL-2 in PNH Subjects
Scientific title
A Phase Ib, Open Label, Multiple Ascending Dose, Pilot Study to Assess the Safety, Preliminary Efficacy and Pharmacokinetics of Subcutaneously Administered APL-2 in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)
Secondary ID [1] 0 0
APL2-CP-PNH-204
Universal Trial Number (UTN)
Trial acronym
PADDOCK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paroxysmal Nocturnal Hemoglobinuria 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APL-2

Experimental: Cohort 1 - 180 mg APL-2/day

Experimental: Cohort 2 - 270 mg APL-2/day


Treatment: Drugs: APL-2
Complement (C3) Inhibitor

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2.Severity of treatment emergent adverse events (TEAEs) following administration of multiple doses of SC APL-2.
Timepoint [1] 0 0
change from baseline
Primary outcome [2] 0 0
LDH (U/L)
Timepoint [2] 0 0
change from baseline
Primary outcome [3] 0 0
Haptoglobin (mg/dL) & Hemoglobin (g/dl)
Timepoint [3] 0 0
change from baseline

Eligibility
Key inclusion criteria
- Male or female

- At least 18 years old (inclusive)

- Weigh >55 kg and have a body mass index (BMI) =38.0 kg/m2

- Diagnosed with PNH (white blood cell (WBC) clone >10%)

- Lactose dehydrogenase (LD) =2 times the upper limit of normal

- Last transfusion within 12 months prior to screening

- Platelet count of >30,000/mm3

- Absolute neutrophil count >cells/500 µL

- 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

- Males must agree to use protocol defined methods of contraception and agree to refrain
from donating sperm for the duration of the study

- Able to provide documentary evidence of Neisseria meningitidis, Pneumococcal conjugate
vaccine (multivalent) or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23) and
Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 dosing,
OR willing to receive vaccinations against Neisseria meningitidis at least two weeks
prior to dosing on Day 1 with a booster on Day 57, and PCV13 and Hib vaccines at least
two weeks prior to dosing on Day 1.

- Willing and able to give informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior eculizumab (Soliris)® treatment

- Active bacterial infection

- Known infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)

- Hereditary complement deficiency

- History of bone marrow transplantation

- Concurrent severe aplastic anemia (SAA), defined as currently receiving
immunosuppressive therapy for SAA including but not limited to cyclosporin A,
tacrolimus, mycophenolate mofetil or anti-thymocyte globulin.

- Participation in any other investigational drug trial or exposure to another
investigational agent, device or procedure within 30 days

- Evidence of QTcF prolongation defined as >450 ms for males and >470 ms for females at
screening

- Creatinine clearance (CrCl) <50 mL/min (Cockcroft-Gault formula) at screening

- Breast-feeding women

- History of meningococcal disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Hong Kong
State/province [1] 0 0
Hong Kong
Country [2] 0 0
Malaysia
State/province [2] 0 0
Selangor
Country [3] 0 0
New Zealand
State/province [3] 0 0
Waikato
Country [4] 0 0
Thailand
State/province [4] 0 0
Bangkok

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Apellis Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

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

An exploratory objective of the study is to assess the pharmacodynamics (PD) of multiple SC
doses of APL 2 when administered to PNH patients.
Trial website
https://clinicaltrials.gov/show/NCT02588833
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Federico Grossi, MD, PhD
Address 0 0
Apellis Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications