Efficacy and Safety Study of Multiple Doses of VIT-2763 in Adults With Transfusion-dependent Beta-thalassemia

Phase 2

Withdrawn

• Conditions: Beta-Thalassemia
• Interventions: Drug: VIT-2763 120 mg BID; Drug: VIT-2763 60 mg QD; Drug: VIT-2763 60 mg BID; Drug: Placebo

• Registration Number: NCT04938635
• Lead Sponsor: Vifor (International) Inc.

Brief Summary

The main purpose of this study is to evaluate the efficacy of 3 multiple doses of VIT-2763 as measured by the reduction in red blood cell (RBC) transfusion burden from Week 13 to Week 24, to identify the most efficacious and safe dose.

Detailed Description

All patients giving written informed consent will undergo a 12-week screening period to determine eligibility for study entry. At Day 1, patients who meet the eligibility requirements will be randomized in a double-blind manner to 1 of 4 treatment groups: VIT-2763 60 mg (once daily), 60 mg (twice daily), or 120 mg (twice daily) or placebo.

The randomisation will be stratified (balanced allocation across treatment groups) according to β0/β0 genotype (yes/no).

The duration of the treatment with VIT-2763 or placebo is 24 weeks, after which patients will undergo a 12-week post-treatment follow-up period.

Study Timeline

• Study First Submitted: 2021-06-16
• Study First Submitted QC: 2021-06-16
• Study First Posted: 2021-06-24
• Study Start: 2021-09-20
• Status Verified: 2022-03
• Last Update Submitted: 2022-11-07
• Last Update Posted: 2022-11-10
• Primary Completion: 2023-07
• Study Completion: 2023-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Body weight ≥40.0 kg and ≤100 kg at screening
• Documented diagnosis of beta-thalassemia or Hb E/beta-thalassemia
• Red blood cell (RBC) transfusion dependence, defined as at least 6 RBC units in the 24 weeks prior to randomization and no transfusion-free period for ≥35 days during that period
• Ability to understand the requirements of the study and provide written informed consent

Exclusion Criteria

• Documented diagnosis of Hb S/beta-thalassemia, alpha-thalassemia, or delta beta (δβ)-thalassemia, or hereditary persistence of foetal Hb.
• History of partial or total splenectomy within 4 months prior to screening.
• History of myocardial iron overload
• Chronic liver disease or history of liver cirrhosis
• Clinically relevant renal disease
• History or clinically important finding of cardiac disorders
• History of clinically significant lung disease
• Uncontrolled hypertension (> Grade 1 according to NCI CTCAE current version)
• Unable to take and absorb oral medications.
• Pregnancy or breastfeeding
• History of drug or alcohol abuse within 2 years prior to screening
• History or concomitant solid tumors and/or hematological malignancies unless resolved in the ≥5 past years.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VIT-2763 120 mg BID	VIT-2763 120 mg BID	VIT-2763 120 mg administered twice daily
VIT-2763 60 mg QD	VIT-2763 60 mg QD	VIT-2763 60 mg administered once daily
VIT-2763 60 mg BID	VIT-2763 60 mg BID	VIT-2763 60 mg administered twice daily
Placebo	Placebo	Placebo capsule administered twice daily

Primary Outcome Measures

Name	Time	Method
Proportion of patients achieving ≥33% reduction of RBC transfusions from baseline and a reduction of ≥2 units assessed consecutively from Week 13 to Week 24 compared to the baseline transfusion	Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1)

Secondary Outcome Measures

Name	Time	Method
Proportion of patients achieving ≥33% reduction of RBC transfusions and ≥2 units assessed over any consecutive 12-week interval from Week 1 to 24.	Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1)
Change from baseline in RBC transfusions over Weeks 13 to 24 compared to the baseline RBC transfusion burden derived using the last 12 weeks prior to randomization.	Week 13 to Week 24 comparing to Baseline (Day -83 to Day 1)
Proportion of patients achieving ≥50% reduction of RBC transfusions and ≥2 units assessed over any consecutive 12-week interval from Week 1 to 24.	Any consecutive 12-week interval from Week 1 to Week 24 comparing to Baseline (Day -83 to Day 1)
Mean change from baseline in Quality of Life (QoL) total score	Week 15 and Week 24 comparing to Baseline (Day 1)	Transfusion-dependent QoL Questionnaire (TranQuol): a disease-specific, validated, QoL measure developed for thalassemia patients. The adult version includes 36 questions grouped into 5 domains: physical health, emotional health, sexual health, family functioning, and school/career functioning. The total score ranges from 0 (worst) to 100 (best).

Trial Locations

Locations (7)

Investigator site #710; 🇺🇸 Whittier, California, United States

Investigational site #804; 🇧🇬 Stara Zagora, Bulgaria

Investigational site #802; 🇧🇬 Plovdiv, Bulgaria

Investigator Site 404; 🇮🇱 Jerusalem, Israel

Investigator Site 405; 🇮🇱 Safed, Israel

Investigational site #801; 🇧🇬 Sofia, Bulgaria

Investigator Site 406; 🇮🇱 Petah tikva, Israel