Paroxysmal Nocturnal Hemoglobinuria (PNH)Phase 1NCT02264639
A Phase I Study to Assess the Safety of Pegcetacoplan (APL-2) as an Add-On to Standard of Care in Subjects With PNH
A Phase 1 study testing Pegcetacoplan in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Apellis Pharmaceuticals, Inc. at 7 sites in United States.
Trial summary
This study will be the initial exploration of pegcetacoplan in patients with PNH. The assessments of the safety, tolerability, PK, and PD following administration of single and multiples doses of pegcetacoplan will guide decisions to further develop the drug. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria (PNH)
- What is being tested?
- Pegcetacoplan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 7 sitesUnited States
- Study dates
- 23 Feb 2015to 22 Oct 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or Female
- At least 18 years of age
- Weigh >55 kg
- Diagnosed with PNH
- On treatment with eculizumab (Soliris®) for at least 3 months
- Hb < 10 g/dL at screening OR have received at least one transfusion within 12 months prior to screening
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- Platelet count of >30,000/mm3
- Absolute neutrophil count > 500/mm3
- 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 (see below)
- Males with female partners of child bearing potential must agree to use protocol defined methods of contraception (see below) and agree to refrain from donating sperm for the duration of the study
- Willing and able to give informed consent
Who cannot join
- Active bacterial infection
- Known infection with hepatitis B, C or HIV
- Hereditary complement deficiency
- History of bone marrow transplantation
- Participation in any other investigational drug trial or exposure to other 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
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- Creatinine clearance (CrCl) < 50 mL/min (Cockcroft-Gault formula) at screening
- Breast-feeding women
- History of meningococcal disease
- No vaccination against N. meningitidis types A, C, W, Y and B (administered as two separate vaccinations), Pneumococcal conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, respectively) and Haemophilus influenzae Type B (Hib) vaccination within 2 years prior to Day 1 (Visit 2) dosing.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
John Hopkins Hospital
Baltimore, Maryland, 21231
Cleveland Clinic
Cleveland, Ohio, 44195
Duke University Medical Center
Durham, North Carolina, 27710
Cure 4 The Kids Foundation
Las Vegas, Nevada, 89135
University of Southern California Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Lousiville
Louisville, Kentucky, 40202
Lakes Research
Miami Lakes, Florida, 33014
About this study
Official title: An Open Label, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL-2 as an Add-On to Standard of Care in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).
This study will be the initial exploration of pegcetacoplan in patients with PNH. The assessments of the safety, tolerability, PK, and PD following administration of single and multiples doses of pegcetacoplan will guide decisions to further develop the drug.
- Being tested
- Pegcetacoplan
- Keywords
- PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, hematologic diseases, extravascular hemolysis (EVH), intravascular hemolysis (IVH), C3 inhibitor
- Medical subject headings
- Hemoglobinuria, Paroxysmal, Anemia, Hemoglobinuria, Hematologic Diseases, Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegcetacoplanDrug
Also called APL-2
Complement (C3) Inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | First Dose 25mg, Repeated Dose 5 mg/day Receives: Drug: Pegcetacoplan |
| Cohort 2 | Experimental | First Dose 50 mg, Repeated Dose 30 mg/day Receives: Drug: Pegcetacoplan |
| Cohort 3 | Experimental | Repeated Dose 180 mg/day Receives: Drug: Pegcetacoplan |
| Cohort 4 | Experimental | Repeated Dose 270 mg/day Receives: Drug: Pegcetacoplan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase
TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
Measured: From single dose of study drug (Day 1) up to 30 days
Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase
TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
Measured: From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).
Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4
Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.
Measured: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4
Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.
Measured: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2014 (estimated)
- Study start23 Feb 2015
- Primary completion22 Oct 2018
- Study completion22 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Paroxysmal Nocturnal Hemoglobinuria (PNH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Apellis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Federico Grossi, MD, PhD, Study director, Apellis Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02264639
- Sponsor's protocol ID
- APL-CP0514
- Status last verified
- Dec 2020
- First submitted
- 8 Oct 2014
- Last updated
- 8 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of APL-2 as an Add-On to Standard of Care in Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH).
- ClinicalTrials.gov ID
- NCT02264639
- Acronym / sponsor ID
- APL-CP0514
- Keywords
- PNH, Paroxysmal Nocturnal Hemoglobinuria, Complement inhibitor, Anemia, Hemoglobinuria, hematologic diseases, extravascular hemolysis (EVH), intravascular hemolysis (IVH)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Apellis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 23 Feb 2015 (actual)
- Primary completion
- 22 Oct 2018 (actual)
- Study completion
- 22 Oct 2018 (actual)
- First posted
- 15 Oct 2014 (estimated)
- Results
- Posted 8 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be the initial exploration of pegcetacoplan in patients with PNH. The assessments of the safety, tolerability, PK, and PD following administration of single and multiples doses of pegcetacoplan will guide decisions to further develop the drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: PegcetacoplanFirst Dose 25mg, Repeated Dose 5 mg/day |
| Cohort 2 | Experimental | Drug: PegcetacoplanFirst Dose 50 mg, Repeated Dose 30 mg/day |
| Cohort 3 | Experimental | Drug: PegcetacoplanRepeated Dose 180 mg/day |
| Cohort 4 | Experimental | Drug: PegcetacoplanRepeated Dose 270 mg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or Female
- At least 18 years of age
- Weigh >55 kg
- Diagnosed with PNH
- On treatment with eculizumab (Soliris®) for at least 3 months
Key exclusion criteria (10 listed)
- Active bacterial infection
- Known infection with hepatitis B, C or HIV
- Hereditary complement deficiency
- History of bone marrow transplantation
- Participation in any other investigational drug trial or exposure to other investigational agent, device or procedure within 30 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PegcetacoplanAlso: APL-2Complement (C3) Inhibitor | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase
Time frame: From single dose of study drug (Day 1) up to 30 days
TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
Number of Subjects With TEAEs, Including by Severity, During Multiple-dose Phase
Time frame: From first dose of study drug up to 30 days after last dose of study drug (Cohorts 1-3: up to 58 days; Cohort 4: up to 759 days).
TEAEs were defined as AEs that developed or worsened after first dose of study drug (Day 1), and up to 30 days after last dose of study drug. The Investigator assessed AEs for severity and relatedness to study drug. AEs were graded according to CTCAE, v4.03 based on: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to AE.
Area Under the Curve (AUC) From Time 0 to the Last Measurable Concentration (AUC0-t) Over the Multiple Dosing Phase for Cohort 4
Time frame: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
Assessment of AUC0-t of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach and calculated by the linear-log trapezoidal method. Pegcetacoplan pharmacokinetic (PK) parameters were summarized for Cohort 4 only.
Maximum Pre-dose Serum Concentration (Ctrough,Max) Over the Multiple Dosing Phase for Cohort 4
Time frame: Blood samples for PK assessment were collected pre-dose and 4 hours post dose on Day 1 and pre-dose (trough) on Day 2 and up to Day 785.
Assessment of Ctrough,max of pegcetacoplan over the multiple dosing phase, estimated using a non-compartmental approach. Pegcetacoplan PK parameters were summarized for Cohort 4 only. Ctrough,max was calculated for both 270 mg/day and 360 mg/day where subjects received both doses. Note: 1 subject in Cohort 4 who was receiving 360 mg/day was granted Sponsor and institutional review board approval to increase the dose further to the equivalent of 440 mg/day and Ctrough,max is also reported for this dose.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Federico Grossi, MD, PhD study director
Apellis Pharmaceuticals, Inc.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pegcetacoplan in people with Paroxysmal Nocturnal Hemoglobinuria (PNH), run by Apellis Pharmaceuticals, Inc. at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Including by Severity, During Single-dose Phase (time frame: From single dose of study drug (Day 1) up to 30 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2021; AzTrials last refreshed its copy on 7 Nov 2026.