A Study on the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of CAN106 in Subjects With PNH

NCT05539248 | Unknown Phase 1

• 2 other identifiers: CAN106-PNH-102/201CTR20220162
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

PNH; Hemolysis

Keywords

C5 complement inhibitor; CAN106; PNH

Outcome Measures

Primary Outcomes (2)

• 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)

  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.

  Baseline, Day 182

Secondary Outcomes (13)

• Area Under the Curve (AUC) - Pharmacokinetics parameter

  182 days

• Maximum Plasma Concentration (Cmax) - Pharmacokinetics parameter

  182 days

• Time to Maximum Concentration (Tmax) - Pharmacokinetics parameter

  182 days

• t1/2 - Pharmacokinetics parameter

  182 days

• PD parameters-free C5

  182 days

Study Arms (3)

Dose escalation CAN106 in cohort 1

EXPERIMENTAL

Subjects are administered CAN106 20 mg/kg IV maintenance dosing.

Drug: CAN106 20 mg/kg

Dose escalation CAN106 in cohort 2

EXPERIMENTAL

Subjects are administered CAN106 40 mg/kg IV maintenance dosing.

Drug: CAN106 40 mg/kg

Dose escalation CAN106 in cohort 3

EXPERIMENTAL

Subjects are administered CAN106 80 mg/kg IV maintenance dosing.

Drug: CAN106 80 mg/kg

Interventions

CAN106 20 mg/kg DRUG

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;

Dose escalation CAN106 in cohort 1

CAN106 40 mg/kg DRUG

Induction and maintenance dosing for cohort 2: 30 mg/kg on Day 1, and 40mg/kg on Day 8 and every 4 weeks thereafter；

Dose escalation CAN106 in cohort 2

CAN106 80 mg/kg DRUG

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.

Dose escalation CAN106 in cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• CARE Pharma Shanghai Ltd.: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Hemolysis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bing Han, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• Hongzhong Liu, MMed

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tianci Kou

CONTACT

+86 21 52996609; tianci.kou@canbridgepharma.com

Chuting Zhang

CONTACT

chuting.zhang@canbridgepharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: September 14, 2022
• Study Start: March 25, 2022
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: September 14, 2022

Record last verified: 2022-07

Locations

CN (1)