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

• ClinicalTrials.gov Identifier: NCT04887506
• Recruitment Status: Completed
• First Posted: May 14, 2021
• Last Update Posted: November 4, 2022
• Sponsor: Tavanta Therapeutics
• Information provided by (Responsible Party): Tavanta Therapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Castration-resistant Prostate Cancer; Metastatic Castration-sensitive Prostate Cancer; Metastatic Prostate Cancer	Drug: TAVT-45; Drug: Zytiga; Drug: Prednisone	Phase 3

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 mCSPC and mCRPC. Randomization will be stratified by prostate cancer population (CSPC vs CRPC) and baseline testosterone (<10 vs ≥ 10 ng/dL). Patients will be 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) + 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 14, 2021
• Actual Primary Completion Date: August 5, 2022
• Actual Study Completion Date: October 20, 2022

Arms and Interventions

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, administered twice daily.; Drug: Prednisone; mCSPC patients will receive 5 mg orally once daily. mCRPC patients will receive 5 mg orally twice daily.; Other Name: 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: Zytiga; 500 mg tablet, administered twice daily.; Other Name: Abiraterone Acetate; Drug: Prednisone; mCSPC patients will receive 5 mg orally once daily. mCRPC patients will receive 5 mg orally twice daily.; Other Name: Encorton

Outcome Measures

Primary Outcome Measures :

1. Testosterone Levels [ Time Frame: Average over Day 9 and Day 10 ]
   Blood samples collected to measure serum testosterone in order to demonstrate equivalent pharmacodynamic effect between TAVT-45 and reference abiraterone acetate (R-AA)

Secondary Outcome Measures :

1. Percent of Subjects With PSA-50 Response [ Time Frame: Over 84 days ]
   Blood samples collected to measure prostate-specific antigen (PSA). The PSA-50 response is defined as a decrease of ≥ 50% in PSA levels from baseline
2. Testosterone Levels [ Time Frame: Days 28, 56 and 84 ]
   Blood samples collected to measure serum testosterone levels
3. Percent of Subjects With PSA-50 Response [ Time Frame: Days 28, 56, and 84 ]
   Blood samples collected to measure PSA in order to determine PSA-50
4. PSA Levels [ Time Frame: Days 28, 56, and 84 ]
   Blood samples collected to measure PSA
5. Trough concentrations of abiraterone [ Time Frame: Days 9, 28, 56, and 84 ]
   Blood samples collected to measure plasma concentrations of abiraterone (trough sample to be collected before next dose)
6. Pharmacokinetic analysis of AUC [ Time Frame: Days 1 and 9 ]
   Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling
7. Pharmacokinetic analysis of Cmax [ Time Frame: Days 1 and 9 ]
   Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling
8. Pharmacokinetic analysis of Cmin [ Time Frame: Days 1 and 9 ]
   Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling
9. Pharmacokinetic analysis of Tmax [ Time Frame: Days 1 and 9 ]
   Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling
10. Pharmacokinetic analysis of Rac [ Time Frame: Days 1 and 9 ]
    Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling
11. Pharmacokinetic analysis of t1/2 [ Time Frame: Days 1 and 9 ]
    Blood samples collected to measure plasma concentrations of abiraterone in a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling

Eligibility Criteria

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

Criteria

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 enrolment
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 CYP3A4 inducers at 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:

    • 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)
    • SGOT (AST): ≤ 2.5 x ULN
    • SGPT (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 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.

Contacts and Locations

Locations

United States, Alabama

Research Site

Homewood, Alabama, United States, 35209

United States, Arizona

Research Site

Tucson, Arizona, United States, 85715

United States, Arkansas

Research Site

Little Rock, Arkansas, United States, 72211

United States, California

Research Site

Los Angeles, California, United States, 90048

Research Site

San Bernardino, California, United States, 92404

United States, Colorado

Research Site

Denver, Colorado, United States, 80211

United States, Florida

Research Site

Bradenton, Florida, United States, 34205

United States, Idaho

Research Site

Meridian, Idaho, United States, 83642

United States, Indiana

Research Site

Jeffersonville, Indiana, United States, 47130

United States, Maryland

Research Site

Annapolis, Maryland, United States, 21401

United States, Michigan

Research Site

Troy, Michigan, United States, 48084

United States, New York

Research Site

New York, New York, United States, 10016

United States, Virginia

Research Site

Virginia Beach, Virginia, United States, 23462

France

Research Site

Suresnes, Hauts-de-Seine, France, 92151

Hungary

Research Site

Budapest, Hungary, 1062

Research Site

Budapest, Hungary, 1122

Research Site

Debrecen, Hungary, 4032

Poland

Research Site

Warszawa, Masovia, Poland, 02-351

Research Site

Bydgoszcz, Poland, 85-048

Research Site

Lublin, Poland, 20-718

Research Site

Piaseczno, Poland, 05-500

Research Site

Warszawa, Poland, 02-119

Puerto Rico

Research Site

Ponce, Puerto Rico, 00731

Spain

Research Site

Madrid, Arturo Soria, 270, Spain, 28033

Research Site

Madrid, Av. Reyes Católicos 2, Spain, 28040

Research Site

Manresa, Barcelona, Spain, 08243

Research Site

Madrid, Calle De Oña 10, Spain, 28050

Research Site

Barcelona, Sabadell, Spain, 08208

Research Site

Barcelona, Spain, 08041

Research Site

Barcelona, Spain, 08907

Research Site

Lleida, Spain, 25198

Research Site

Madrid, Spain, 28041

Research Site

Sevilla, Spain, 41013

Sweden

Research Site

Gothenburg, Sweden, SE-413 45

Research Site

Västerås, Sweden, SE-721 89

United Kingdom

Research Site

Torquay, Devon, United Kingdom, TQ2 7AA

Research Site

Cheltenham, Gloucestershire, United Kingdom, GL53 7AN

Research Site

Hampstead, London, United Kingdom, NW3 2QS

Research Site

Glasgow, Scotland, United Kingdom, G12 0YN

Research Site

Guildford, Surrey, United Kingdom, GU2 7XX

Research Site

London, United Kingdom, SW3 6JJ

Sponsors and Collaborators

Tavanta Therapeutics

Investigators

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

More Information

Additional Information:

Sponsors website 

• Responsible Party: Tavanta Therapeutics
• ClinicalTrials.gov Identifier: NCT04887506
• Other Study ID Numbers: TAVT45C02; 2020-005611-46 ( EudraCT Number )
• First Posted: May 14, 2021
• Last Update Posted: November 4, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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

• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• 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
• 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).

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tavanta Therapeutics:

Prostate; Metastatic; Cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Prednisone; Abiraterone Acetate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors