Clinical Trials Register

Summary
EudraCT Number:	2020-005611-46
Sponsor's Protocol Code Number:	TAVT45C02
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-04-17
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2020-005611-46

A.3

Full title of the trial

Phase 3 study investigating the efficacy and safety of TAVT-45 (abiraterone acetate) Granules for Oral Suspension (a novel abiraterone acetate formulation) relative to a reference abiraterone acetate formulation in patients with metastatic Castrate Sensitive Prostate Cancer (mCSPC) and metastatic Castrate Resistant Prostate Cancer (mCRPC).

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Phase 3 study to investigate the safety and efficacy of a new formulation of an existing drug product called TAVT-45 in patients with metastatic prostate cancer

A.4.1

Sponsor's protocol code number

TAVT45C02

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Tavanta Therapeutics, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Tavanta Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Tavanta Therapeutics, Inc.
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	101 E. Baltimore Ave, # 602
B.5.3.2	Town/ city	Media, PA
B.5.3.3	Post code	19063
B.5.3.4	Country	United States
B.5.4	Telephone number	+1833776 8963

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	TAVT-45
D.3.4	Pharmaceutical form	Granules for oral suspension in sachet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABIRATERONE ACETATE
D.3.9.1	CAS number	154229-18-2
D.3.9.2	Current sponsor code	TAVT-45
D.3.9.3	Other descriptive name	ABIRATERONE ACETATE
D.3.9.4	EV Substance Code	SUB31647
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Zytiga
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International N.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Zytiga
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ABIRATERONE ACETATE (Zytiga)
D.3.9.1	CAS number	154229-18-2
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	ABIRATERONE ACETATE
D.3.9.4	EV Substance Code	SUB31647
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic Castrate Sensitive Prostate Cancer (mCSPC) and metastatic
Castrate Resistant Prostate Cancer (mCRPC)

E.1.1.1

Medical condition in easily understood language

Prostate Cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10060862
E.1.2	Term	Prostate cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10076506
E.1.2	Term	Castration-resistant prostate cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Establish equivalence between TAVT-45 granules and Zytiga tablets in patients with metastatic Castrate Sensitive Prostate Cancer (mCSPC) and metastatic Castrate Resistant Prostate Cancer (mCRPC).

E.2.2

Secondary objectives of the trial

Characterize the multiple-dose pharmacokinetic profile of TAVT-45 in a cohort of patients.

E.2.3

Trial contains a sub-study

E.3

Principal 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, as defined below:
a). CSPC: Using the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) system, patients must have Tany Nany M+ (distant metastases) disease AND two of the following:
-Gleason score of 8 or greater
-Three or more bone scan lesions
-Measurable visceral metastases
b). CRPC: Patients must have metastatic* disease, and must also have disease progression according to the recommendations of the Prostate Cancer Working Group 3 by having at least one of the following criteria:
-Two rises of PSA (taken a minimum of 1 week apart) from a baseline measurement of at least 1 ng/mL
-Imaging progression (CT/MRI) by RECIST 1.1 criteria or PET/CT*
-Nuclear scan progression by 2 or more new bone lesions.
*Note: Metastatic disease should be documented by MRI/CT, PET/CT (including, but not limited to, standard of care imaging using 18F-fluciclovine, 11C-choline, or PSMA where approved) or bone scan. Imaging obtained within 90 days prior to the start of study drug/reference product will be accepted.
6. The following prior treatment and or surgery for prostate cancer are allowed:
a) CSPC:
i) 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
ii) 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
iii) Radiation or surgical therapy that was not initiated 4 weeks after the start of ADT or orchiectomy
b) CRPC:
i). 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 assessments

E.4

Principal 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:
a) Prior treatment with abiraterone or enzalutamide is prohibited
b) 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, non-muscle 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.

E.5 End points

E.5.1

Primary end point(s)

Efficacy: The primary efficacy endpoint is the comparison of the average of serum testosterone levels on days 9 and 10 between groups (TAVT-45 vs R-AA).
Safety: Safety endpoints include incidence of treatment emergent adverse events (TEAE), and clinically relevant changes in vital signs and laboratory assessments.
Pharmacokinetics: For a cohort of up to 8 patients randomized to TAVT-45 and participating in the serial PK sampling on Day 1 and Day 9, the following PK parameters will be determined:
a) Area under the concentration-time curve from time zero to 12 hours post dose (AUC0-12)
b) Maximum measured plasma concentration (Cmax)
c) Minimum measured plasma concentration (Cmin)
d) Time to maximum measured concentration (tmax)
e) Accumulation ratio (Rac)
f) Effective half-life (t½)

E.5.1.1

Timepoint(s) of evaluation of this end point

Average of serum testosterone levels will be compared between groups on Days 9 and 10.

A cohort of 8 patients randomized to TAVT-45 will participate in serial PK sampling on Days 1 and 9.

E.5.2

Secondary end point(s)

The key secondary efficacy endpoint is the PSA-50 response, defined as a decrease of ≥50% in PSA levels from baseline at any time over the 84-day post-treatment period.
Other secondary efficacy endpoints are as follows:
a) Serum testosterone levels at Days 28, 56 and 84
b) PSA-50 response at Days 28, 56 and 84
c) PSA levels at Days 28, 56 and 84
d) Trough concentrations of abiraterone at Days 9, 28, 56 and 84

E.5.2.1

Timepoint(s) of evaluation of this end point

a) Serum testosterone levels at Days 28, 56 and 84
b) PSA-50 response at Days 28, 56 and 84
c) PSA levels at Days 28, 56 and 84
d) Trough concentrations of abiraterone at Days 9, 28, 56 and 84

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

France

Germany

Hungary

Poland

Spain

Sweden

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of study is defined as the date of the last patient last visit (i.e., the Visit 10 follow-up phone call for patients completing the trial as planned, or the Early Termination Visit for patients who are treated but discontinue prior to completing the Day 84 visit [see Table 1: Assessment schedule]).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

108

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

A follow-up phone call will be made approximately one week after the last dose for AE assessments.
There is no post-trial access to study medication after patients complete this trial; instead investigators will prescribe the local standard-of-care treatment for metastatic prostate cancer, if clinically indicated.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-06-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-10-20

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