Chronic Immune Thrombocytopenia
Conditions
Keywords
Purpura, Thrombocytopenic, Idiopathic
Brief summary
The goal of the global Phase 1/2 clinical trial is to evaluate whether CID-103, a novel anti-CD38 monoclonal antibody, is safe and effective in adults with chronic immune thrombocytopenia (ITP). The main questions the study aims to answer are: * To evaluate the safety and tolerability of CID-103 in subjects with ITP with different increasing doses of CID-103. * To further evaluate the safety and tolerability of CID-103 at two or three dose levels and to select an optimal dose and administration regimen for CID-103 for further study of clinical efficacy. The study will be done in two parts: Part A will test increasing doses of CID-103 to see how safe it is and how well people tolerate it. Researchers will also aim to find a safe dose range. Part B will compare up to three different doses of CID-103 to see how well the medicine works and gather more safety and efficacy information. The goal is to find the optimal dose to use in future studies. CID-103 is given through an intravenous (IV) infusion. During the study, participants may receive treatment for up to 6 months, followed by a post-treatment safety follow-up period to check for ongoing safety and effectiveness. This study is an important step toward developing a new treatment for people living with chronic ITP. If CID-103 is found to be safe and effective, it could offer a new option for patients who do not respond well to current therapies.
Interventions
DRUGCID-103
Strength:20 mg/mL. Route of administration: IV infusion. Treatment duration: QW for 6 weeks, then at the same dose Q2W up to Week 12. If treatment continues after Week 12, dosing will occur monthly for up to a maximum treatment duration of six months.
Sponsors
CASI Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A (Dose Escalation and Safety Phase): This phase combines the accelerated escalation and traditional 3+3 escalation with at least five dosing cohorts designed:30 mg, 150 mg, 300 mg, 600 mg, and 900 mg. Subjects will receive an initial priming dose of either 30 mg for the first two cohorts or 150 mg for the rest of cohorts. Dose escalation to the next cohort will be determined based on safety and tolerability data. Part B (Randomized Dose Comparison Phase): This phase follows a parallel assignment model, in which participants are randomly assigned to one of three selected doses of CID-103: low, intermediate, or high. The purpose is to determine the optimal dose to advance into future studies.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female individuals aged 18 to 65 years at time of signing of ICF. Disease-related. 2. Diagnosed with ITP that has persisted for ≥ 3 months, diagnosed in accordance with The American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia or the Updated International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia (as locally applicable). 3. Diagnosis of ITP supported by a prior response to an ITP treatment (other than a thrombopoietin receptor agonists \[TPO-RA\]) that achieved a platelet count of ≥ 30 x 10\^9/L and a doubling of baseline measurement. 4. Has received at least two lines of SOC systemic treatment (i.e., corticosteroids and one other agent). 5. Has a mean platelet count ≤ 35 x 10\^9/L on at least two measurements at least one week apart during screening. 6. If receiving standard background treatment for ITP, treatment should be stable in dose and frequency for at least four weeks prior to first dose of CID-103. 7. Adequate organ function. 8. Contraception: Female participants must either be non-pregnant or not breastfeeding and must have a negative pregnancy test. Male and female participants must meet the contraceptive requirements.
Exclusion criteria
1. Prior treatment with any anti-CD38 agent, or has been treated with anti-Bruton's tyrosine kinase (BTK), neonatal Fc receptor (FcRn) antagonist or complement inhibitor within three months prior to first dose of CID-103. 2. Use of IV immunoglobulin, subcutaneous immunoglobulin or anti-D immunoglobulin treatment within four weeks of screening. 3. Treatment with rituximab or splenectomy within the three months prior to first dose of CID-103. 4. Use of anticoagulants or any drug with antiplatelet effect (such as aspirin) within three weeks before screening. 5. Receiving other concurrent investigational therapies or have received investigational therapies within four weeks of the first dose of CID-103 or five half-lives (if shorter). 6. Active hemolytic anemia. 7. Diagnosed with severe chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease (GOLD Stage 3 or 4) or asthma. 8. Has been diagnosed with myelodysplastic syndrome or other active malignancy. 9. Known / clinically significant amyloidosis. 10. Has a history of any thrombotic or embolic event within six months before screening. 11. A history or evidence of cardiovascular risk including left ventricular ejection fraction \< 50%, clinically significant uncontrolled ventricular arrhythmia, acute coronary syndrome history, coronary angioplasty or stenting within six months, current ≥ Class III congestive heart failure (NYHA guidelines), and treatment refractory hypertension. 12. Clinically significant medical history or ongoing chronic illness. 13. Known active infection with hepatitis B (HBV) (surface antigen) or infection with hepatitis C (HCV) in absence of sustained virologic response. 14. History of known or suspected immunosuppression. 15. Known active infection with human immunodeficiency virus (HIV) and CD4+ T cell count \< 350/μL. 16. Karnofsky Performance Status ≤ 70.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of CID-103 | 10 months | * Occurrence of DLTs (Part A only) * Frequency of TEAEs * Related AEs * Grade 3/4 AEs * Serious adverse events (SAEs) * Fatal AEs * AEs leading to CID-103 discontinuation up to Week 12 * Percentage of subjects with at least one treatment-related Grade ≥ 3 TEAE, SAE or AE leading to CID-103 discontinuation up to Week 12 (Part B only) |
| Platelet response | 12 weeks | A platelet count ≥ 50 x 10\^9/L and ≥ 20 x 10\^9/L above baseline achieved on at least two consecutive measurements at least seven days apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet count | 12 weeks | The secondary efficacy endpoint is Platelet count, defined as platelet count ≥ 30 x 10\^9/L and \> 2-fold increase in platelet count from baseline and absence of bleeding requiring medical intervention / treatment, measured on at least two consecutive occasions at least seven days apart. |
| Complete platelet response | 12 weeks | The secondary efficacy endpoint includes percentage of subjects with complete platelet response, defined as platelet count ≥ 100 x 109/L and absence of bleeding requiring medical intervention / treatment, measured on at least two consecutive occasions at least seven days apart. |
Countries
China
Contacts
Primary ContactAaron Yang
Outcome results
None listed