Paroxysmal Nocturnal HemoglobinuriaPhase 2NCT05476887
To Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104
A Phase 2 study testing KP104 in people with Paroxysmal Nocturnal Hemoglobinuria, run by Kira Pharmacenticals (US), LLC. at 4 sites in China.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of KP104 in complement inhibitor-naïve participants with PNH. The study will be conducted in 2 parts. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- KP104
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 4 sitesChina
- Study dates
- 25 Nov 2022to Feb 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Initial Treatment Period:
- Documented diagnosis of PNH confirmed by flow cytometry evaluation of white blood cells and red blood cells, with granulocyte or monocyte clone size of >= 10 percent (%) within 6 months of the Screening visit.
- Presence of 1 or more PNH-related signs or symptoms within 3 months of initiation of Screening.
- LDH >= 2.0 × upper limit of normal (ULN) at screening.
- Hemoglobin <= 10.0 g/dL at screening.
- Females of childbearing potential and males must practice effective contraception from Screening until 28 days after the end of study (EOS) visit.
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- Females of childbearing potential must have a negative pregnancy test at Screening and within 24 hours prior to dosing of study drug.
- Extension Treatment Period (OLE):
- Complete the 12-week (weekly dosing) or 13-week (biweekly dosing) Initial Treatment Period per the protocol.
- Benefited from KP104 treatment and will continue benefiting from KP104 treatment per the investigator's judgement.
- Willing to participate in Extension Treatment Period, able to comply with this protocol and be available for the entire duration of the study.
Who cannot join
- Initial Treatment Period:
- Any clinically significant poorly controlled underlying illness other than PNH per discretion of investigators.
- Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibiotics, antivirals, or antifungals.
- History of meningococcal infection.
- History of untreated tuberculosis.
- History of splenectomy
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- Positive serology for Hepatitis C Virus (HCV) ribonucleic acid (RNA) or human immunodeficiency virus (HIV) at Screening
- History of bone marrow or stem cell transplantation
- Absolute neutrophil count (ANC) <500 cells per microliter (cells/μL)
- Reticulocyte count< 100 x 10^3 cells/μL
- Platelet count< 30,000 cells/μL
- History of systemic autoimmune disease
- Estimated glomerular filtration rate (eGFR) <30 milliliters/minute/1.73 meter square (mL/min/1.73 m^2) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
- Extension Treatment Period (OLE):
- Women who are pregnant.
- Women of childbearing potential and men with sexual partners of childbearing potential who are not using adequate contraception and who are not willing to use adequate contraception.
- Any medical condition that, in the opinion of the investigator, may pose a safety risk to a participant in this study, or may interfere with study participation.
- Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
4 sites in 1 country.
China4 sites
Peking Union Medical College Hospital
Beijing
Jiangsu Province Hospital
Nanjing
Chinese Academy of Medical Sciences Peking Union Medical College - Institute of Hematology Blood Diseases Hospital
Tianjin
Henan Cancer Hospital
Zhengzhou
About this study
Official title: An Open-label, Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104 in Complement Inhibitor-naïve Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)
The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of KP104 in complement inhibitor-naïve participants with PNH. The study will be conducted in 2 parts. Part 1 is a dose-selection study to assess escalating doses and varying dose intervals of KP104. Part 2 is a proof-of-concept (POC) study assessing the efficacy of the optimal intravenous (IV) loading dose followed by the optimal maintenance dose and regimen of KP104. Participants who complete the Initial Treatment Period and demonstrate benefit from KP104 will be eligible for a 9-month open-label extension (OLE) treatment period.
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- KP104
- Keywords
- KP104, Paroxysmal nocturnal hemoglobinuria, Complement Inhibitor, Dose Selection, Proof of Concept
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KP104Drug
KP104 intravenously (IV loading + subcutaneous [SC] maintenance every week [QW] or every 2 weeks [Q2W]) will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Dose escalation Cohort 1 | Experimental | Participants will receive escalating and varying dose intervals of KP104 every week. Receives: Drug: KP104 |
| Part 1: Dose escalation Cohort 2 | Experimental | Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly. Receives: Drug: KP104 |
| Part 1: Dose escalation Cohort 3 | Experimental | Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly. Receives: Drug: KP104 |
| Part 2: Proof-of-concept Cohort 1 | Experimental | Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly. Receives: Drug: KP104 |
| Open-label extension (OLE) | Experimental | Participants will receive KP104, who benefit from KP104 treatment in Part 1 and 2 Receives: Drug: KP104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Number of participants with Dose-limiting toxicities (DLT)
A DLT is defined as any adverse event considered by the investigator to be KP104-related with a severity greater than or equal to (>=) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 3 which also represents a shift from baseline clinical status of > 1 NCI CTCAE grade. A hypersensitivity/administration reaction occurring with a severity of Grade 2 despite the use of pre-medications will also be designated as a DLT.
Measured: Up to Week 4
Part 2: Percentage of participants with >= 2 grams per deciliter (g/dL) increase in hemoglobin level from Baseline in the absence of transfusion for weekly dosing
Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.
Measured: Baseline and at Week 12
Part 2: Percentage of participants with >= 2 g/dL increase in hemoglobin level from Baseline in the absence of transfusion for biweekly dosing
Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.
Measured: Baseline and at Week 13
Open-label Extension (OLE): Number of participants reporting Treatment Emergent Adverse Events (TEAEs), treatment-emergent serious adverse events (TESAEs) and AEs of special interest (AESIs)
Measured: Up to 9 months
Secondary outcomes (9)
Part 2: Change from Baseline in serum lactate dehydrogenase (LDH) levels for weekly dosing
Blood samples will be collected for the analysis of serum LDH.
Measured: Baseline and at Week 12
Part 2: Change from Baseline in serum LDH levels for biweekly dosing
Blood samples will be collected for the analysis of serum LDH.
Measured: Baseline and at Week 13
Part 2: Change from Baseline in hemoglobin level for weekly dosing
Blood samples will be collected for the analysis of hemoglobin level
Measured: Baseline and at Week 12
Part 2: Change from Baseline in the hemoglobin level for biweekly dosing
Blood samples will be collected for the analysis of hemoglobin level.
Measured: Baseline and at Week 13
Part 2: Change from Baseline in red blood cell (RBC) transfusion dependence for weekly dosing
The RBC transfusion dependence is the difference in the volume of RBC transfusions per month for the 3 months prior to initiation of investigational product versus the volume of RBC transfusions per month for each month on study.
Measured: Baseline and at Week 12
Part 2: Change in RBC transfusion dependence for biweekly dosing
The RBC transfusion difference is the difference in the volume of RBC transfusions per month for the 3 months prior to initiation of investigational product versus the volume of RBC transfusions per month for each month on study.
Measured: Baseline and at Week 13
Part 1 and 2: Number of participants reporting TEAEs, TESAEs and AESIs
Measured: Up to Week 13
Part 1 and 2: Concentration within one hour of end of infusion (CEOI) of KP104
Measured: Up to Week 13
Part 1 and 2: Trough concentration (Ctrough) of KP104
Measured: Up to Week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2022
- Study start25 Nov 2022
- Primary completionNov 2024 (estimated)
- Study completionFeb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kira Pharmacenticals (US), LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05476887
- Sponsor's protocol ID
- KP104-201
- Status last verified
- Oct 2024
- First submitted
- 25 Jul 2022
- Last updated
- 28 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of KP104 in Complement Inhibitor-naïve Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)
- ClinicalTrials.gov ID
- NCT05476887
- Acronym / sponsor ID
- KP104-201
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Keywords
- KP104, Paroxysmal nocturnal hemoglobinuria, Complement Inhibitor, Dose Selection, Proof of Concept
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Kira Pharmacenticals (US), LLC.Industry (pharma, biotech, devices)
- Study start
- 25 Nov 2022 (actual)
- Primary completion
- Nov 2024 (estimated)
- Study completion
- Feb 2025 (estimated)
- First posted
- 27 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, pharmacodynamics, and efficacy of KP104 in complement inhibitor-naïve participants with PNH. The study will be conducted in 2 parts. Part 1 is a dose-selection study to assess escalating doses and varying dose intervals of KP104. Part 2 is a proof-of-concept (POC) study assessing the efficacy of the optimal intravenous (IV) loading dose followed by the optimal maintenance dose and regimen of KP104. Participants who complete the Initial Treatment Period and demonstrate benefit from KP104 will be eligible for a 9-month open-label extension (OLE) treatment period.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1: Dose escalation Cohort 1 | Experimental | Drug: KP104Participants will receive escalating and varying dose intervals of KP104 every week. |
| Part 1: Dose escalation Cohort 2 | Experimental | Drug: KP104Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly. |
| Part 1: Dose escalation Cohort 3 | Experimental | Drug: KP104Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly. |
| Part 2: Proof-of-concept Cohort 1 | Experimental | Drug: KP104Participants will receive escalating and varying dose intervals of KP104 weekly or biweekly. |
| Open-label extension (OLE) | Experimental | Drug: KP104Participants will receive KP104, who benefit from KP104 treatment in Part 1 and 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Documented diagnosis of PNH confirmed by flow cytometry evaluation of white blood cells and red blood cells, with granulocyte or monocyte clone size of >= 10 percent (%) within 6 months of the Screening visit.
- Presence of 1 or more PNH-related signs or symptoms within 3 months of initiation of Screening.
- LDH >= 2.0 × upper limit of normal (ULN) at screening.
- Hemoglobin <= 10.0 g/dL at screening.
- Females of childbearing potential and males must practice effective contraception from Screening until 28 days after the end of study (EOS) visit.
Key exclusion criteria (18 listed)
- Any clinically significant poorly controlled underlying illness other than PNH per discretion of investigators.
- Treatment of any infection with IV (within 30 days of Screening) or oral (within 14 days of Screening) antibiotics, antivirals, or antifungals.
- History of meningococcal infection.
- History of untreated tuberculosis.
- History of splenectomy
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 |
|---|---|---|
| KP104KP104 intravenously (IV loading + subcutaneous [SC] maintenance every week [QW] or every 2 weeks [Q2W]) will be administered. | Drug | Open-label extension (OLE), Part 1: Dose escalation Cohort 1, Part 1: Dose escalation Cohort 2, Part 1: Dose escalation Cohort 3, Part 2: Proof-of-concept Cohort 1 |
Primary outcome
Part 1: Number of participants with Dose-limiting toxicities (DLT)
Time frame: Up to Week 4
A DLT is defined as any adverse event considered by the investigator to be KP104-related with a severity greater than or equal to (>=) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 3 which also represents a shift from baseline clinical status of > 1 NCI CTCAE grade. A hypersensitivity/administration reaction occurring with a severity of Grade 2 despite the use of pre-medications will also be designated as a DLT.
Part 2: Percentage of participants with >= 2 grams per deciliter (g/dL) increase in hemoglobin level from Baseline in the absence of transfusion for weekly dosing
Time frame: Baseline and at Week 12
Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.
Part 2: Percentage of participants with >= 2 g/dL increase in hemoglobin level from Baseline in the absence of transfusion for biweekly dosing
Time frame: Baseline and at Week 13
Blood samples will be collected for the analysis of increase in hemoglobin levels in the absence of transfusion.
Open-label Extension (OLE): Number of participants reporting Treatment Emergent Adverse Events (TEAEs), treatment-emergent serious adverse events (TESAEs) and AEs of special interest (AESIs)
Time frame: Up to 9 months
9 secondary outcomes
Part 2: Change from Baseline in serum lactate dehydrogenase (LDH) levels for weekly dosing
Time frame: Baseline and at Week 12
Part 2: Change from Baseline in serum LDH levels for biweekly dosing
Time frame: Baseline and at Week 13
Part 2: Change from Baseline in hemoglobin level for weekly dosing
Time frame: Baseline and at Week 12
Part 2: Change from Baseline in the hemoglobin level for biweekly dosing
Time frame: Baseline and at Week 13
Part 2: Change from Baseline in red blood cell (RBC) transfusion dependence for weekly dosing
Time frame: Baseline and at Week 12
Part 2: Change in RBC transfusion dependence for biweekly dosing
Time frame: Baseline and at Week 13
Part 1 and 2: Number of participants reporting TEAEs, TESAEs and AESIs
Time frame: Up to Week 13
Part 1 and 2: Concentration within one hour of end of infusion (CEOI) of KP104
Time frame: Up to Week 13
Part 1 and 2: Trough concentration (Ctrough) of KP104
Time frame: Up to Week 13
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2024.
- Individual participant dataSharing planned: Yes
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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.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KP104 in people with Paroxysmal Nocturnal Hemoglobinuria, run by Kira Pharmacenticals (US), LLC. at 4 sites in China.
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 18 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: status not confirmed, as of the sponsor's last update on 28 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in China. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Part 1: Number of participants with Dose-limiting toxicities (DLT) (time frame: Up to Week 4). 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 28 Oct 2024.