PNHPhase 1/2NCT05539248
A Study on the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of CAN106 in Subjects With PNH
A Phase 1/2 study testing CAN106 20 mg/kg, CAN106 40 mg/kg and CAN106 80 mg/kg in people with PNH and Hemolysis, run by CARE Pharma Shanghai Ltd. at 1 site in China.
Trial summary
The purpose of the study is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of CAN106 administered intravenously to subjects with PNH who have not previously been treated with a complement inhibitor. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- CAN106 20 mg/kg, CAN106 40 mg/kg and CAN106 80 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteChina
- Study dates
- 25 Mar 2022to Dec 2025
- Phase
- Phase 1/2
- 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
- Male or female patients ≥18 years of age.
- Body weight ≥40 kg at screening.
- Documented diagnosis of PNH within 6 months prior to screening, confirmed by high-sensitivity flow cytometry evaluation of red blood cells (RBCs), with granulocyte or monocyte clone size of ≥10%.
- LDH level ≥ 1.5 X ULN at screening.
- Mean hemoglobin(Hb)<10 g/dL for those who have not received blood. transfusion at screening, based on 2 measurements from separate blood samples collected at interval of 2-8 weeks apart prior to the first dosing. Or hemoglobin < 10 g/dL at the first screening and then with subsequent red blood cell transfusions.
- Presence of 1 or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia (hemoglobin < 10 g/dL), history of a major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction; or history of pRBC transfusion due to PNH.
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- All patients must be vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug. Patients who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination.
- If available, Haemophilus influenzae type b and Streptococcus pneumoniae vaccines can be administered according to national vaccine guidelines, and antibiotic prophylaxis should be given until 2 weeks after vaccination if the vaccines are administered within 14 days prior to administration.
- All females of childbearing potential and all males must be willing to use at least one highly effective method of contraception from signing of informed consent until 8 months after the last dose of CAN106 Injection; Male subjects with female partners of childbearing potential must be willing to use condoms in addition to using a highly effective method of contraception.
- Subjects should be willing to sign the informed consent forms and comply with the study visit.
Who cannot join
- Current or previous treatment with a complement inhibitor.
- Positive pregnancy test on day 1, or female patients who are planning to become pregnant or are pregnant or breastfeeding.
- Participation in an interventional clinical study within 28 days before initiation of dosing on Day 1, or within 5 half-lives of the investigational product, whichever is greater.
- Platelet count < 30 × 10^9/L at Screening.
- Absolute neutrophil count < 0.5 × 10^9/L at Screening.
- Alanine aminotransferase (ALT) > 3 × ULN, or both direct bilirubin and alkaline phosphatase (ALP) > 2 × ULN during the screening period.
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- Serum creatinine > 2.5 × ULN and creatinine clearance < 30 mL/min as calculated by the Cockcroft-Gault formula during the screening period.
- History of malignancy within 5 years of Screening with the exception of nonmelanoma skin cancer or carcinoma in situ of the cervix that has been treated with no evidence of recurrence.
- History of bone marrow transplantation.
- Major surgery within 90 days prior to screening.
- History of N. meningitidis infection or unexplained, recurrent infection.
- Known or suspected hereditary complement deficiency.
- Active systemic bacterial, viral, or fungal infection within 14 days prior to dosing
- Presence of fever ≥38°C within 7 days prior to study drug administration.
- Having received splenectomy within 6 months prior to screening.
- Known history of severe allergic or anaphylactic reactions to antibiotics and are unwilling to use prophylaxis as specified in the protocol.
- Patients are excluded if they are taking any of the following medications and are not on a stable regimen(as judged by investigator) for the time period indicated prior to screening:
- Erythropoietin or immunosuppressants for at least 8 weeks;
- Corticosteroids for at least 4 weeks;
- Vitamin K antagonists with a stable international normalized ratio for 4 weeks;
- Iron supplements or folic acid for at least 4 weeks;
- Low molecular weight heparin for at least 4 weeks.
- Known allergy to excipients of CAN106 or allergy to Chinese hamster ovary cell proteins.
- Immunization with a live-attenuated vaccine 1 month prior to dosing on day 1.
- Known or suspected history of drug or alcohol abuse or dependence within 1 year prior to the start of Screening.
- Inability to comply with study requirements.
- History of or ongoing major cardiac, pulmonary, renal, endocrine, or hepatic disease (eg, active hepatitis) that, in the opinion of the Investigator or Sponsor, precludes the patient's participation in an investigational clinical trial.
- Known medical or psychological condition(s) or risk factor that, in the opinion of the Investigator, might interfere with the patient's full participation in the study, pose any additional risk for the patient, or confound the assessment of the patient or outcome of the study.
Trial locations and contacts
1 site in 1 country.
Chuting Zhang contact
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Tianci Kou, tianci.kou@canbridgepharma.com
Bing Han, MD
About this study
Official title: A Multicenter, Open-label, Multiple Ascending Dose Phase 1b/2 Trial to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of CAN106 Intravenously in Subjects With PNH Naïve to Complement-Inhibitor Treatment
The purpose of the study is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of CAN106 administered intravenously to subjects with PNH who have not previously been treated with a complement inhibitor.
Read the detailed description
This is an open-label, multiple dose escalation study to assess the safety, tolerability, efficacy, PK, PD and immunogenicity of CAN106 given as an IV infusion. The data presented is up to the primary completion date of the study and is for the 26-week primary evaluation period. The study also includes an extension period of up to 52 weeks.
- Being tested
- CAN106 20 mg/kg, CAN106 40 mg/kg, CAN106 80 mg/kg
- Keywords
- C5 complement inhibitor, CAN106, PNH
- Medical subject headings
- Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAN106 20 mg/kgDrug
Induction and maintenance dosing for cohort 1:
12 mg/kg on Day 1, 16 mg/kg on Day 8, and 20 mg/kg on Day 15 and every 4 weeks thereafter;
CAN106 40 mg/kgDrug
Induction and maintenance dosing for cohort 2:
30 mg/kg on Day 1, and 40mg/kg on Day 8 and every 4 weeks thereafter；
CAN106 80 mg/kgDrug
Induction and maintenance dosing for cohort 3:
60 mg/kg on day 1, and 80 mg/kg on day 15 and every 8 weeks thereafter.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation CAN106 in cohort 1 | Experimental | Subjects are administered CAN106 20 mg/kg IV maintenance dosing. Receives: Drug: CAN106 20 mg/kg |
| Dose escalation CAN106 in cohort 2 | Experimental | Subjects are administered CAN106 40 mg/kg IV maintenance dosing. Receives: Drug: CAN106 40 mg/kg |
| Dose escalation CAN106 in cohort 3 | Experimental | Subjects are administered CAN106 80 mg/kg IV maintenance dosing. Receives: Drug: CAN106 80 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of treatment-emergent adverse events (TEAEs) of multiple doses of CAN106 as assessed by CTCAE v5.(Phase 1b)
TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 28 days after the last dose of CAN106, include adverse events (AEs), serious adverse events (SAEs), AEs of special interest (AESIs), abnormal laboratory data compared with baseline, vital signs, and electrocardiograms (ECGs)
Measured: 182 days
Percent Change In Lactate Dehydrogenase (LDH) Levels Normalization From Baseline to Day 182(Phase 2)
Baseline is defined as the average of all available assessments prior to first CAN106 infusion.
Measured: Baseline, Day 182
Secondary outcomes (13)
Area Under the Curve (AUC) - Pharmacokinetics parameter
Area under the plasma concentration versus time curve to the last visit (AUC)
Measured: 182 days
Maximum Plasma Concentration (Cmax) - Pharmacokinetics parameter
Peak plasma concentration
Measured: 182 days
Time to Maximum Concentration (Tmax) - Pharmacokinetics parameter
Time to reach maximum of concentration (days)
Measured: 182 days
t1/2 - Pharmacokinetics parameter
Terminal elimination half-life
Measured: 182 days
PD parameters-free C5
Maximal change from baseline in free C5 concentrations at each of scheduled post baseline assessment time-points (µg/ml)
Measured: 182 days
PD parameters-CH50
Maximal change from baseline total complement activity (CH50) at each of scheduled post baseline assessment time-points (%)
Measured: 182 days
PD parameters- total C5
Measure the absolute change from baseline in total C5 concentrations at each of scheduled post baseline assessment time-points (µg/ml)
Measured: 182 days
Immunogenicity
Anti-drug Antibody (ADA) titers
Measured: 182 days
Changes from Baseline in Serum Lactate Dehydrogenase (LDH) Level
Changes from baseline in serum LDH level to Day 182
Measured: 182 days
Percent Change In Free Hemoglobin Level From Baseline to Day 182
Changes from baseline in free hemoglobin level at each of the scheduled post-baseline time-points
Measured: 182 days
Percent Change In Haptoglobin Levels From Baseline to Day 182
Changes in haptoglobin from baseline to each of the scheduled post-baseline time-points
Measured: 182 days
Changes in scores of patient-reported outcomes as measured by FACIT-Fatigue from Baseline to Day 182
The FACIT-F is a 13-item, self-reported PRO measure assessing an individual's level of fatigue during their usual daily activities over the past week. This questionnaire is part of the FACIT measurement system, a compilation of questions measuring health-related QoL in patients with cancer and other chronic illnesses. The FACIT-fatigue assesses the level of fatigue using a 4-point Likert scale ranging from 0 (not at all) to 4 (very much). Scores range from 0 to 52, with higher scores indicating greater fatigue
Measured: 182 days
Changes in scores of patient-reported outcomes as measured by European Organization for Research and Treatment of Cancer [EORTC]- Quality of life questionnaire-core 30 (QLQ-30)
EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All the scales range from 0 to 100. A high score on the functional scales represents a high level of functioning, and a high score on the symptom scales represents a high level of symptomatology
Measured: 182 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2022
- Study start25 Mar 2022
- Primary completionDec 2024 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PNHStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CARE Pharma Shanghai Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bing Han, MD, Principal investigator, Peking Union Medical College HospitalHongzhong Liu, MMed, Principal investigator, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05539248
- Sponsor's protocol ID
- CAN106-PNH-102/201
- Other IDs
- CTR20220162
- Status last verified
- Jul 2022
- First submitted
- 7 Jul 2022
- Last updated
- 14 Sep 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Multiple Ascending Dose Phase 1b/2 Trial to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of CAN106 Intravenously in Subjects With PNH Naïve to Complement-Inhibitor Treatment
- ClinicalTrials.gov ID
- NCT05539248
- Acronym / sponsor ID
- CAN106-PNH-102/201
- Keywords
- C5 complement inhibitor, CAN106, PNH
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- CARE Pharma Shanghai Ltd.Industry (pharma, biotech, devices)
- Study start
- 25 Mar 2022 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 14 Sep 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 the study is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of CAN106 administered intravenously to subjects with PNH who have not previously been treated with a complement inhibitor.
Detailed description
This is an open-label, multiple dose escalation study to assess the safety, tolerability, efficacy, PK, PD and immunogenicity of CAN106 given as an IV infusion. The data presented is up to the primary completion date of the study and is for the 26-week primary evaluation period. The study also includes an extension period of up to 52 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose escalation CAN106 in cohort 1 | Experimental | Drug: CAN106 20 mg/kgSubjects are administered CAN106 20 mg/kg IV maintenance dosing. |
| Dose escalation CAN106 in cohort 2 | Experimental | Drug: CAN106 40 mg/kgSubjects are administered CAN106 40 mg/kg IV maintenance dosing. |
| Dose escalation CAN106 in cohort 3 | Experimental | Drug: CAN106 80 mg/kgSubjects are administered CAN106 80 mg/kg IV maintenance dosing. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patients ≥18 years of age.
- Body weight ≥40 kg at screening.
- Documented diagnosis of PNH within 6 months prior to screening, confirmed by high-sensitivity flow cytometry evaluation of red blood cells (RBCs), with granulocyte or monocyte clone size of ≥10%.
- LDH level ≥ 1.5 X ULN at screening.
- Mean hemoglobin(Hb)<10 g/dL for those who have not received blood. transfusion at screening, based on 2 measurements from separate blood samples collected at interval of 2-8 weeks apart prior to the first dosing. Or hemoglobin < 10 g/dL at the first screening and then with subsequent red blood cell transfusions.
Key exclusion criteria (28 listed)
- Current or previous treatment with a complement inhibitor.
- Positive pregnancy test on day 1, or female patients who are planning to become pregnant or are pregnant or breastfeeding.
- Participation in an interventional clinical study within 28 days before initiation of dosing on Day 1, or within 5 half-lives of the investigational product, whichever is greater.
- Platelet count < 30 × 10^9/L at Screening.
- Absolute neutrophil count < 0.5 × 10^9/L at Screening.
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 |
|---|---|---|
| CAN106 20 mg/kgInduction and maintenance dosing for cohort 1: 12 mg/kg on Day 1, 16 mg/kg on Day 8, and 20 mg/kg on Day 15 and every 4 weeks thereafter; | Drug | Dose escalation CAN106 in cohort 1 |
| CAN106 40 mg/kgInduction and maintenance dosing for cohort 2: 30 mg/kg on Day 1, and 40mg/kg on Day 8 and every 4 weeks thereafter； | Drug | Dose escalation CAN106 in cohort 2 |
| CAN106 80 mg/kgInduction and maintenance dosing for cohort 3: 60 mg/kg on day 1, and 80 mg/kg on day 15 and every 8 weeks thereafter. | Drug | Dose escalation CAN106 in cohort 3 |
Primary outcome
Incidence and severity of treatment-emergent adverse events (TEAEs) of multiple doses of CAN106 as assessed by CTCAE v5.(Phase 1b)
Time frame: 182 days
TEAEs were defined as adverse events (AE) that occurred after dosing on Day 1 and up to 28 days after the last dose of CAN106, include adverse events (AEs), serious adverse events (SAEs), AEs of special interest (AESIs), abnormal laboratory data compared with baseline, vital signs, and electrocardiograms (ECGs)
Percent Change In Lactate Dehydrogenase (LDH) Levels Normalization From Baseline to Day 182(Phase 2)
Time frame: Baseline, Day 182
Baseline is defined as the average of all available assessments prior to first CAN106 infusion.
13 secondary outcomes
Area Under the Curve (AUC) - Pharmacokinetics parameter
Time frame: 182 days
Maximum Plasma Concentration (Cmax) - Pharmacokinetics parameter
Time frame: 182 days
Time to Maximum Concentration (Tmax) - Pharmacokinetics parameter
Time frame: 182 days
t1/2 - Pharmacokinetics parameter
Time frame: 182 days
PD parameters-free C5
Time frame: 182 days
PD parameters-CH50
Time frame: 182 days
PD parameters- total C5
Time frame: 182 days
Immunogenicity
Time frame: 182 days
Changes from Baseline in Serum Lactate Dehydrogenase (LDH) Level
Time frame: 182 days
Percent Change In Free Hemoglobin Level From Baseline to Day 182
Time frame: 182 days
Percent Change In Haptoglobin Levels From Baseline to Day 182
Time frame: 182 days
Changes in scores of patient-reported outcomes as measured by FACIT-Fatigue from Baseline to Day 182
Time frame: 182 days
Changes in scores of patient-reported outcomes as measured by European Organization for Research and Treatment of Cancer [EORTC]- Quality of life questionnaire-core 30 (QLQ-30)
Time frame: 182 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2022.
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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.
Chuting Zhang contact
Bing Han, MD principal investigator
Peking Union Medical College Hospital
Hongzhong Liu, MMed principal investigator
Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CAN106 20 mg/kg, CAN106 40 mg/kg and CAN106 80 mg/kg in people with PNH and Hemolysis, run by CARE Pharma Shanghai Ltd. at 1 site 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 10 inclusion and 28 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 14 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
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?
Contact Tianci Kou (+86 21 52996609 ext. 807, tianci.kou@canbridgepharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of treatment-emergent adverse events (TEAEs) of multiple doses of CAN106 as assessed by CTCAE v5.(Phase 1b) (time frame: 182 days). The study lists 2 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 14 Sep 2022.