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Completed

NCT Number: NCT03271541

A Study of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent (NTD) Beta-Thalassemia

This proof-of-mechanism study is being performed to investigate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of multiple oral doses of bitopertin in adults with NTD beta-thalassemia.

This study consists of two parts:

Part 1 - The main study - 16 weeks in total: Participants will undergo a 6-week dose-escalation period followed by 10 weeks of treatment at the attained target dose.

Part 2 - Open Label Extension (OLE) - up to an additional 12 months. Participants will be given the option to enroll into the OLE once the 16-week treatment of Part 1 has been completed. Participants who decide not to enroll in the OLE, at the end of Part 1 will enter a 6-week follow-up period.

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Key information

Conditions

Beta-Thalassemia Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Thalassemia

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Centro della Microcitemia e delle Anemie Congenite - Ospedale Galliera; Oncologia /Cardiologia, Genoa, Liguria, Italy

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Confirmed diagnosis of beta-thalassemia
  • Clinically defined non-transfusion-dependent anemia (Part 1 only), defined as Hb concentrations >7.5 grams per deciliter (g/dL) and <9.5 g/dL, less than or equal to 4 transfusions of red blood cell units within 1 year prior to study enrollment, and no transfusion within 12 weeks prior to study enrollment
  • Completion of 16 weeks of treatment with bitopertin in Part 1 of this study with more than 80% compliance from expected use of study medication (based on patient diary and study drug accountability; Part 2 only)
  • A favorable benefit-risk ratio from treatment with bitopertin as assessed by the Investigator (Part 2 only)

Exclusion criteria

  • Any history of gene therapy
  • History of hemolytic anemia except for beta-thalassemia
  • Severe symptomatic splenomegaly and/or hepatomegaly with hypersplenism (Part 1 only)
  • Any use of an erythropoiesis-stimulating agent within 24 weeks prior to enrollment.
  • Initiation of iron chelation therapy or hydroxyurea within 24 weeks prior to enrollment (Part 1 only)
  • Depression, treatment with anti-depressants, or other psychiatric illnesses and/or drug abuse
  • Clinically significant/uncontrolled comorbid disease
  • Pregnant or breastfeeding females
  • Use of cytochrome P450 (CYP) 3A4 inhibitors within 2 weeks or CYP3A4 inducers within 4 weeks prior to study drug
  • Active hepatitis B or C or known positive human immunodeficiency virus (HIV) test result
  • Diagnosis of cancer within previous 5 years unless treatment has resulted in complete freedom from disease for at least 2 years
  • Any major illness within 1 month or febrile illness within 1 week prior to study drug
  • Pulmonary hypertension requiring oxygen therapy (Part 1 only)

Treatment and study plan

bitopertin

Drug

Bitopertin will be administered orally once daily at doses up to 120 milligrams (mg).

Other names: RO4917838

Primary outcomes

  1. Safety Outcome: Percentage of Participants with Adverse Events (AEs) - Part 1 only

    Time frame: Baseline, Week 16, up to Week 22

  2. Efficacy Outcome: Change in Total Hemoglobin (Hb) Level from Baseline to End of 16-Week Treatment Period in Part 1

    Time frame: Baseline to Week 16

  3. Long-term Safety Outcome : Percentage of Participants with Adverse Events (AEs) - Part 2 only

    Time frame: Baseline to 19 Months

Secondary outcomes

  1. Apparent Clearance of Bitopertin

    Time frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks

  2. Volume of Distribution of Bitopertin

    Time frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks

  3. Area Under the Concentration-Time Curve (AUC) of Bitopertin within a Dosing Interval

    Time frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks

  4. Minimum Observed Concentration (Cmin) of Bitopertin

    Time frame: Part 1: Predose (0 H) on Days 2, 15, 29, 57, 85, 113; and at early withdrawal (up to 22 weeks overall). Part 2: Predose (0 H) and postdose (1, 4 H) on Days 183, 365; and at early withdrawal (up to 65 weeks overall)

  5. Maximum Observed Concentration (Cmax) of Bitopertin

    Time frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks

  6. Apparent Elimination Half-Life of Bitopertin

    Time frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks

  7. Accumulation Ratio of Bitopertin

    Time frame: Part 1: 2,12 hours (H) postdose (PD) on Day 1; 0 H predose (PRD) on Day 2; 0H PRD and 3H PD on Days 15,29,57; 0H PRD and 1,4H PD on Day 85; 0H PRD on Day 113; early withdrawal (ED) up to 22 wks. Part 2: 0H PRD and 1,4H PD on Days 183,365; ED up to 65 wks

  8. Change from Baseline in Absolute Reticulocyte Count

    Time frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65

  9. Change from Baseline in Serum Lactate Dehydrogenase Level

    Time frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65

  10. Change from Baseline in Serum Bilirubin Level

    Time frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65

  11. Change from Baseline in Absolute Red Blood Cell Count

    Time frame: Part 1: Baseline, Week 16. Part 2: Up to Week 65

  12. Change in Total Hb Level from Baseline to the End of the Treatment Period in Part 2

    Time frame: Baseline, 19 Months

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase II, Single Arm, Multicenter, Proof-of-Mechanism Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Bitopertin (RO4917838) in Adults With Non-Transfusion-Dependent Βeta-Thalassemia

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Sep 5, 2017
Registry last updated
Oct 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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