A Study of HG146 Capsule in Chinese Subjects with Relapsed and Refractory Multiple Myeloma

Phase 1

Terminated

• Conditions: Multiple Myeloma; Relapsed and Refractory Multiple Myeloma
• Interventions: Drug: HG146

• Registration Number: NCT03710915
• Lead Sponsor: HitGen Inc.

Brief Summary

This study is designed to evaluate the tolerability and safety of HG146 capsule in patients with multiple myeloma.

Detailed Description

This study is mainly designed to evaluate the tolerability and safety of HG146 capsule in patients with multiple myeloma. Secondly, to get pharmacokinetic data and preliminary efficacy of HG146 capsule in human.

This study adopts the traditional design of "3 + 3" dose escalation. The starting dose is 5 mg and subsequent dose group is respectively for 10, 15 and 20 mg. For each dosing group, subjects are administered orally HG146 every other day for two weeks, followed by one week of rest with 21-day as one treatment cycle. Patients will be treated for 4 cycles or disease progression or unacceptable toxicities, whichever comes first.

Study Timeline

• Study First Submitted: 2018-09-29
• Study First Submitted QC: 2018-10-15
• Study First Posted: 2018-10-18
• Study Start: 2019-01-12
• Primary Completion: 2022-09-28
• Study Completion: 2023-06-28
• Status Verified: 2023-09
• Last Update Submitted: 2024-10-08
• Last Update Posted: 2024-10-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

• Diagnosis of multiple myeloma requiring systemic therapy (International Myeloma Working Group [IMWG]) and 2 cycles of treatment including proteasome inhibitors and/or immunomodulators.
• Serum M protein≥ 10.0g / L, or urine M protein ≥ 200mg / 24h.
• Not suitable for autologous bone marrow transplantation or refuse autologous bone marrow transplantation or relapse after autologous bone marrow transplantation.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2.
• Expected survival of ≥3 months.
• Hemoglobin ≥ 80 g/L, Platelet≥75×10^9/L, Absolute Neutrophil Count≧1.0×109/L (1000 cells/mm3), Prothrombin time(PT) and activated partial thromboplastin time ≤ 2 x Upper Limit of Normal (ULN).
• Bilirubin in serum<1.5*ULN (2.0mg/dL/20mg/L/34.2μmol/L); glutamic-pyruvic transaminase (ALT) and/or Aspartate Aminotransferase (AST)≤3*ULN (upper limit of normal).
• Normal electrocardiogram, echocardiography and myocardial enzyme spectrumCalibration of blood calcium concentration≤ULN.
• Men and women, Non-pregnant women who did not consider giving birth during the trial or five years after the end of the trial.
• The patient is able to swallow the capsule.
• Patients must provide written consent.

Exclusion Criteria

• Severe allergies to the study drug or any of its excipients.
• The possibility of gene toxicity, mutagenesis and teratogenicity.
• Men and women who did not have sperm or egg cells stored in vitro before the trial and who planned to have children again within five years.
• Pregnant or lactating women.
• Perform autologous bone marrow transplantation 3 months before admission.
• Receive allogeneic bone marrow transplantation.
• Use HDAC inhibitors before.
• Two weeks prior to admission, received radiotherapy or bone marrow suppressive chemotherapy or biological treatment.
• Patients with history of other malignant tumors, except the tumor is in remission and has not been treated for at least 5 years.
• Patients with dysphagia or oral absorption disorder.
• The investigators determine the conditions not suitable for the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
HG146 capsule treat multiple myeloma	HG146	Experimental: 5/10/15/20 mg HG146 capsule 5 mg starting dose taken orally on Day 1, 3, 5, 7, 9, 11, 13 of each cycle, and off drug for 8 days (3 weeks). Intervention: Drug: HG146 capsule

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of HG146	Up to 3 months	To determine the maximum tolerated dose of HG146 in relapsed and refractory multiple myeloma patients.

Secondary Outcome Measures

Name	Time	Method
Peak Plasma Concentration (Cmax)	In cycle 1 (each cycle is 21 days)	To determine the Peak Plasma Concentration of HG146.
Incidence of adverse events related to treatments	Up to 21 days after last dose	To evaluate the incidence of adverse events that are related to treatments in relapsed and refractory myeloma patients.
Incidence of laboratory abnormalities related to treatments	Up to 1 month after last dose	To evaluate the incidence of laboratory abnormalities that are related to treatments in relapsed and refractory myeloma patients.
Time of Peak Concentration (Tmax)	In the middle of cycle 1 (each cycle is 21 days)	To determine the time of peak concentration of HG146.
Half life (T1/2)	In the middle of cycle 1 (each cycle is 21 days)	To determine the half-life of HG146.
Area under the plasma concentration versus time curve (AUC)	In the middle of cycle 1 (each cycle is 21 days)	To determine the Area under the plasma concentration versus time curve of HG146.

Trial Locations

Locations (1)

HitGen Inc; 🇨🇳 Chengdu, Sichuan, China