TAVT-45 (Abiraterone Acetate) Granules in Patients With Prostate Cancer

Phase 3 Study Investigating the Efficacy and Safety of TAVT-45 (Abiraterone Acetate) Granules for Oral Suspension (Novel Abiraterone Acetate Formulation) Relative to a Reference Abiraterone Acetate Formulation in Patients With mCSPC & mCRPC

The purpose of this study is to investigate the safety and efficacy of a new formulation of an existing drug product called TAVT-45 in patients with metastatic prostate cancer.

Study Overview

• Status: Completed
• Conditions: Metastatic Prostate Cancer; Metastatic Castration-sensitive Prostate Cancer; Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: TAVT-45; Drug: Prednisone; Drug: Zytiga

Detailed Description

This is a Phase 3 randomized, open-label study to evaluate the pharmacodynamic effect and safety profile of TAVT-45 compared to Zytiga (reference abiraterone acetate formulation, hereafter referred to as R-AA) in patients with high-risk metastatic castrate sensitive prostate cancer (mCSPC) and metastatic castrate resistant prostate cancer (mCRPC). Randomization was stratified by prostate cancer population (CSPC vs CRPC) and baseline testosterone (<10 vs ≥ 10 ng/dL). Patients were treated for 84 days and randomized into one of two groups in a 1:1 ratio:

• TAVT-45: Administered twice daily as 1 x sachet containing TAVT-45 (250 mg abiraterone acetate), reconstituted in water or specified fruit juice (orange juice), + Prednisone (5 mg once or twice daily, depending on prostate cancer population)
• R-AA: Administered once daily as (2 x 500 mg Zytiga tablets) + Prednisone (5 mg once or twice daily, depending on prostate cancer population)

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Brest, France, 29200
    • Research Site
  • Hauts-de-Seine
    • Suresnes, Hauts-de-Seine, France, 92151
      • Research Site
• Hungary
  • Budapest, Hungary, 1122
    • Research Site
  • Budapest, Hungary, 1062
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-048
    • Research Site
  • Lublin, Poland, 20-718
    • Research Site
  • Piaseczno, Poland, 05-500
    • Research Site
  • Warszawa, Poland, 02-119
    • Research Site
  • Masovia
    • Warszawa, Masovia, Poland, 02-351
      • Research Site
• Puerto Rico
  • Ponce, Puerto Rico, 00731
    • Research Site
• Spain
  • Barcelona, Spain, 08041
    • Research Site
  • Barcelona, Spain, 08907
    • Research Site
  • Lleida, Spain, 25198
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
  • Arturo Soria, 270
    • Madrid, Arturo Soria, 270, Spain, 28033
      • Research Site
  • Av. Reyes Católicos 2
    • Madrid, Av. Reyes Católicos 2, Spain, 28040
      • Research Site
  • Barcelona
    • Manresa, Barcelona, Spain, 08243
      • Research Site
  • Calle De Oña 10
    • Madrid, Calle De Oña 10, Spain, 28050
      • Research Site
  • Sabadell
    • Barcelona, Sabadell, Spain, 08208
      • Research Site
• Sweden
  • Gothenburg, Sweden, SE-413 45
    • Research Site
  • Västerås, Sweden, SE-721 89
    • Research Site
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Research Site
  • Devon
    • Torquay, Devon, United Kingdom, TQ2 7AA
      • Research Site
  • Gloucestershire
    • Cheltenham, Gloucestershire, United Kingdom, GL53 7AN
      • Research Site
  • London
    • Hampstead, London, United Kingdom, NW3 2QS
      • Research Site
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Research Site
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
      • Research Site
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Research Site
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Research Site
  • California
    • Los Angeles, California, United States, 90048
      • Research Site
    • San Bernardino, California, United States, 92404
      • Research Site
  • Colorado
    • Denver, Colorado, United States, 80211
      • Research Site
  • Florida
    • Bradenton, Florida, United States, 34205
      • Research Site
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Research Site
  • Indiana
    • Jeffersonville, Indiana, United States, 47130
      • Research Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Research Site
  • Michigan
    • Troy, Michigan, United States, 48084
      • Research Site
  • New York
    • New York, New York, United States, 10016
      • Research Site
  • Virginia
    • Virginia Beach, Virginia, United States, 23462
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent obtained prior to any study-related procedure being performed
2. Male patients at least 18 years of age or older at time of consent
3. Pathologically confirmed adenocarcinoma of the prostate
4. Ongoing therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist (unless patient has already had a bilateral orchiectomy) AND serum testosterone level <50 ng/dL at screening
5. Have either metastatic CSPC or metastatic CRPC (per protocol definitions).

6. The following prior treatments and/or surgery for prostate cancer are allowed:

   1. CSPC:

      • Up to 90 days of androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists/antagonists or orchiectomy with or without concurrent anti-androgens prior to patients' randomization is permitted
      • Patients may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease (e.g., impending cord compression or obstructive symptoms) if administered prior to randomization
      • Radiation or surgical therapy that was not initiated 4 weeks after the start of ADT or orchiectomy

   2. CRPC:

      • Previous chemotherapy with docetaxel for metastatic disease with treatment completed at least 1 year prior to screening
7. Discontinuation of flutamide or nilutamide, and other anti-androgens prior to the start of study medication; discontinuation of bicalutamide prior to start of study medication
8. Discontinuation of strong cytochrome P450 3A4 (CYP3A4) inducers at least 4 weeks prior to start of study medication
9. Discontinuation of radiotherapy prior to start of study medication
10. Discontinuation of herbal supplements at least 4 weeks prior to the first dose of study medication and for the duration of the trial.
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at screening

12. Normal organ function with acceptable initial laboratory values within the screening period:

    • Absolute neutrophil count (ANC): ≥ 1,500/μl
    • Albumin: ≥ 3.0g/dL
    • Hemoglobin: ≥ 9g/dL
    • Platelet count: ≥ 100,000/μl
    • Serum Creatinine: ≤ 3.0 x the institutional upper limit of normal (ULN)
    • Potassium: ≥ 3.5 mmol/L (within institutional normal range)
    • Bilirubin: ≤ 1.5 ULN (unless documented Gilbert's disease)
    • Aspartate aminotransferase (AST): ≤ 2.5 x ULN
    • Alanine aminotransferase (ALT): ≤ 2.5 x ULN
13. Life expectancy of at least 6 months at screening
14. Patients engaged in sex with women of child-bearing potential agree to use a condom plus another effective contraception method. Patients agree to use a condom when engaged in any sexual activity, including sex with a pregnant woman. These restrictions will apply from the time informed consent is provided until 3 weeks after the last dose of study medication is taken.
15. Patient is willing and able to comply with all protocol requirements

Exclusion Criteria:

1. For mCSPC patients: any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer not specified as allowable treatment in Inclusion Criterion 6. For example, prior therapy with apalutamide or enzalutamide is prohibited as well as therapy with an investigational agent as described in Exclusion Criterion 16.

2. For mCRPC patients:

   • Prior treatment with abiraterone or enzalutamide is prohibited
   • Previous chemotherapy is prohibited with exception of docetaxel treatment as specified in the inclusion criteria 6.
3. Initiation of bisphosphonate or denosumab therapy within 4 weeks prior to the start of study drug/reference product. Patients who are on a stable dose of these medications for at least 4 weeks at the time of starting study drug/reference product will be eligible.
4. Therapy with estrogen within 4 weeks prior to the start of study drug
5. Use of systemic glucocorticoids equivalent to >10 mg prednisone daily. Patients who have discontinued or reduced dosing to the equivalent of ≤ 10 mg prednisone daily within 14 days prior to the start of study drug are eligible
6. Known, symptomatic metastases to the brain or central nervous system involvement (patients with asymptomatic and neurologically stable disease for the past 4 weeks will be permitted)
7. History of adrenal gland dysfunction defined as requiring treatment for adrenal insufficiency
8. History of other malignancy within the previous 2 years (no longer being actively treated), with the exceptions of basal cell carcinoma, nonmuscle invasive bladder cancer that has been treated and is under surveillance, or other in-situ cancers with a low likelihood of recurrence
9. Major surgery within 4 weeks prior to the start of study drug
10. Known gastrointestinal disease or condition that could impair absorption inclusive of gastrocolic fistula, gastroenterostomy, biliary obstruction, cirrhosis, chronic pancreatitis or pancreatic cancer, cystic fibrosis, lactate deficiency, amyloidosis, celiac disease, Crohn's disease, radiation enteritis, intestinal resection, and history of bariatric surgery
11. Known history of human immunodeficiency virus or seropositive test for hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) (note: HCV patients with undetectable viral load will be eligible)
12. Poorly controlled diabetes, defined as hemoglobin A1c (HbA1c) > 8% within the past 12 months
13. Uncontrolled hypertension at screening
14. History of New York Heart Association class III or IV heart failure
15. Serious concurrent illness, including psychiatric illness, that could interfere with study participation
16. Receipt of another investigational agent within 4 weeks or 5 x the treatment half-life, whichever is longer, of treatment start.
17. Known hypersensitivity or allergy to abiraterone acetate, prednisone or any excipients in the study drugs
18. In the opinion of the investigator, participation in the trial would prevent the patient from receiving local standard-of-care treatment for metastatic prostate cancer, if clinically indicated, after completion of the trial
19. Other condition which, in the opinion of the Investigator, would preclude participation in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAVT-45; TAVT-45 administered twice daily as a 1 x sachet containing TAVT-45 (250 mg abiraterone acetate) + Prednisone (5mg once or twice daily, depending on prostate cancer population). TAVT-45 administered approximately every 12 hours without respect to food. Patients treated for 84 days.	Drug: TAVT-45; 250 mg abiraterone acetate granules for oral suspension in a sachet, reconstituted in water or specified fruit juice (orange juice), administered twice daily.; Drug: Prednisone; mCSPC patients received 5 mg orally once daily. mCRPC patients received 5 mg orally twice daily.; Other Names: Encorton
Active Comparator: Reference abiraterone acetate (Zytiga®) - R-AA; Zytiga (reference abiraterone acetate formulation, hereafter referred to as R-AA) administered once daily as (2 x 500mg Zytiga tablets) + Prednisone (5mg once or twice daily, depending on prostate cancer population). R-AA administered once daily either ≥ 1 hour before or ≥ 2 hours after a meal. Patients treated for 84 days.	Drug: Prednisone; mCSPC patients received 5 mg orally once daily. mCRPC patients received 5 mg orally twice daily.; Other Names: Encorton; Drug: Zytiga; 500 mg tablet, two tablets administered once daily; Other Names: Abiraterone Acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Testosterone (ng/dL) Days 9 and 10 Average (Rounded-up), CR-ITT	The primary endpoint was the between group comparison of serum testosterone levels for the average of levels on Days 9 and 10 (rounded-up) for mCRPC patients.	Average over Day 9 and Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Testosterone (ng/dL) Days 9 and 10 Average (Rounded-up), CS-ITT	This was a supplementary analysis of equivalence, with a between group comparison of serum testosterone for the Days 9 and10 average (rounded-up) values for mCSPC patients treated with either TAVT-45 or R-AA.	Average over Day 9 and Day 10
Serum Testosterone (ng/dL) Days 9 and 10 Average (Rounded-up), mITT	Supplementary analysis of equivalence of TAVT-45 and R-AA on Days 9 and 10 average (rounded-up) values in the mITT population (including mCRPC and mCSPC patients).	Average over Day 9 and Day 10
Percent of Subjects With PSA-50 Response, mITT	The PSA-50 response is defined as a decrease of ≥ 50% in prostate-specific antigen (PSA) levels from baseline.	Response at any time over the 84-day post-treatment period.

Collaborators and Investigators

• Sponsor: Tavanta Therapeutics
• Investigators: Study Chair: Andreas Maetzel, MD, PhD, Tavanta Therapeutics inc.

Publications and helpful links

Helpful Links

• Sponsors website

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2021
• Primary Completion (Actual): October 20, 2022
• Study Completion (Actual): October 20, 2022

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 14, 2021

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Metastatic; Prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Prednisone; Abiraterone Acetate
• Other Study ID Numbers: TAVT45C02; 2020-005611-46 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

According to the Informed Consent Form:

1. The health information that may be used and disclosed includes:

   • All information collected during the research described in the Informed Consent Form for the study; and
   • Health information in my medical records that is relevant to the study.

2. The Providers may disclose health information in my medical records to:

   • Researchers;
   • The Sponsor of the study and its agents and contractors; and
   • Representatives of government agencies, Advarra IRB, and other persons who watch over the safety, effectiveness, and conduct of research.

3. The Researchers may:

   • Use and share patient health information among themselves, with the Sponsor, and with other participating researchers and laboratories to conduct the study; and
   • Disclose health information to representatives of government agencies, review boards

• IPD Sharing Time Frame: The sponsor will store the data for at least 30 years after completion; or discontinuation of the study; or for at least 30 years after the granting of the last marketing authorization until there are no more pending; or contemplated marketing applications; or for at least 30 years after formal discontinuation of the clinical development of the study drug, or are scheduled for submission
• IPD Sharing Access Criteria: The Sponsor will ensure that its affiliated companies or its third-party data processors that analyze data on behalf of the Sponsor treat all patient data in a confidential manner and in accordance with 'The Health Insurance Portability and Accountability Act of 1996' (HIPAA).
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No