Clinical Trials Register

Summary
EudraCT Number:	2020-002021-28
Sponsor's Protocol Code Number:	PLX124-04
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-07-14
Trial 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2020-002021-28

A.3

Full title of the trial

A Multicenter, Open-Label, Parallel, Phase 1b/2a Study of PLX2853 in Combination with Abiraterone Acetate and Prednisone and Phase 1b/2a Study of PLX2853 in Combination with Olaparib in Subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC)

A.3.1

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

A Study to Evaluate PLX2853 in Combination with Abiraterone Acetate/Prednisone and PLX2853 in Combination with Olaparib in Subjects with Metastatic Castration-Resistant Prostate Cancer

A.4.1

Sponsor's protocol code number

PLX124-04

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	Plexxikon 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	Plexxikon 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	Plexxikon Inc.
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	91 Bolivar Drive
B.5.3.2	Town/ city	Berkeley
B.5.3.3	Post code	94710
B.5.3.4	Country	United States
B.5.6	E-mail	PLX12404@plexxikon.com

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	PLX2853
D.3.2	Product code	PLX2853
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.3.11 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	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	Yes
D.2.1.1.1	Trade name	ZYTIGA
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Abiraterone Acetate
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
D.3.9.1	CAS number	154229-18-2
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	range
D.3.10.3	Concentration number	250 to 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.IMP: 3
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	Yes
D.2.1.1.1	Trade name	PREDNISOLONE
D.2.1.1.2	Name of the Marketing Authorisation holder	Wockhardt UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Prednisolone
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	PREDNISOLONE
D.3.9.3	Other descriptive name	PREDNISOLONE
D.3.9.4	EV Substance Code	SUB10018MIG
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	5
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 Castration-Resistant Prostate Cancer (mCRPC)

E.1.1.1

Medical condition in easily understood language

Metastatic Castration-Resistant 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	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.1.2 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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

PLX2853 + abiraterone combination Phase 1b (Dose Escalation)
The primary objective is as follows:
- To evaluate the safety and tolerability of PLX2853 + abiraterone acetate + prednisone including dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) in subjects with mCRPC who develop disease progression while currently receiving initial treatment with abiraterone acetate and prednisone

PLX2853 + abiraterone combination Phase 2a (Dose Expansion)
The primary objective is as follows:
- To evaluate the efficacy of PLX2853 + abiraterone acetate + prednisone at the RP2D in subjects with mCRPC who develop disease progression while currently receiving initial treatment with abiraterone acetate and prednisone

E.2.2

Secondary objectives of the trial

PLX2853 + abiraterone combination Phase 1b (Dose Escalation)
The secondary objective is as follows:
- To characterize the PK of PLX2853 and abiraterone and efficacy of PLX2853 combined with abiraterone acetate + prednisone in subjects with mCRPC who develop disease progression while currently receiving initial treatment with abiraterone acetate and prednisone

PLX2853 + abiraterone combination Phase 2a (Dose Expansion)
The secondary objective is as follows:
- To further characterize the safety and PK of PLX2853 and abiraterone when PLX2853 is combined with abiraterone acetate + prednisone in subjects with mCRPC who develop disease progression while currently receiving initial treatment with abiraterone acetate and prednisone

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥18 years at the time of signing informed consent.
2. Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses.
3. Eastern Cooperative Oncology Group Performance Status 0 to 1.
4. Adequate organ function.
5. Fertile male subjects with female sexual partners must agree to use a highly effective method of birth control during the study and for 90 days after the last dose of study drug.
6. Except as specified above for organ function, all drug-related toxicity from previous cancer therapy (including ongoing abiraterone + prednisone therapy if applicable) must be resolved (to Grade ≤1 or baseline per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) prior to study treatment administration (Grade 2: alopecia, hot flashes, decreased libido, or neuropathy is allowed).
7. Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

E.4

Principal exclusion criteria

1. Prior exposure to a bromodomain inhibitor.
2. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
3. Clinically significant cardiac disease.
4. Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
5. Active known second malignancy with the exception of any of the following:
• Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin.
• Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years.
• Any other cancer from which the subject has been disease-free for ≥3 years.
6. Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed).
7. Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol or would interfere with the study endpoints or the subject’s ability to participate in the study in the judgment of the Investigator.
8. Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with the exception of GnRH therapy with less than protocol defined wash-out.

E.5 End points

E.5.1

Primary end point(s)

PLX2853 + Abiraterone Acetate + Prednisone Combination Phase 1b – Primary Endpoint
• Incidence of DLTs, TEAEs, changes in safety parameters, and unacceptable toxicities

PLX2853 + Abiraterone Acetate + Prednisone Combination Phase 2a – Primary Endpoints
Response as defined by any of the outcomes listed below. If any of these occur, the subject will be considered to have responded.
• Objective response by per RECIST v1.1 with a minimum interval for confirmation of CR and PR of 4 weeks
• PSA decline of ≥50% from baseline, confirmed by a second consecutive PSA assessment at least 3 weeks later
• Conversion of circulating tumor cell count (CTC) to <5 cells/7.5 mL blood nadir confirmed by an additional assessment at least 3 weeks later (for subjects with a CTC count of ≥5 cells/7.5 mL blood at baseline)

E.5.1.1

Timepoint(s) of evaluation of this end point

Phase 1b: Incidence of DLTs, TEAEs, changes in safety parameters, and unacceptable toxicities – C2D1 for DLTs, all timepoints through 30 days after last dose or initiation of new anticancer treatment, whichever occurs first for all toxicities

Phase 2a: Response as defined:
• PSA – D1 of every cycle.
• CTCs - Every 9 weeks through cycle 10, then every 12 weeks (C4D1, C7D1, C10D1, C14D1, C18D1, etc)
• Radiographic Assessment – Every 9 weeks through cycle 10, then every 12 weeks (C4D1, C7D1, C10D1, C14D1, C18D1, etc)

E.5.2

Secondary end point(s)

PLX2853 + Abiraterone Acetate + Prednisone Combination (Phase 1b (Dose Escalation) and Phase 2a (Dose Expansion)):
Secondary Endpoints
• Radiographic progression-free survival (rPFS)
• Time to PSA progression
• Duration of PSA response
• Overall survival defined as the time from the first dose of study drug to the date of death due to any cause
• Incidence of TEAEs, changes in safety parameters, and unacceptable toxicities
• PK parameters of PLX2853 and abiraterone and PLX2853 and olaparib following single and repeated dosing
• BOR per RECIST v1.1
• DOR (time from date of first documented, confirmed response using RECIST v1.1 and PCWG3 until date of documented progression or death from any cause).
• Time to first SSRE defined as:
• Use of radiation therapy to prevent or relieve skeletal symptoms.
• Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). Radiologic documentation is required.
• Occurrence of spinal cord compression. Radiologic documentation required.
• Orthopedic surgical intervention for bone metastasis.

E.5.2.1

Timepoint(s) of evaluation of this end point

• Radiographic progression free survival – Every 9 weeks through cycle 10, then every 12 weeks
• Time to PSA progression – D1 of every cycle
• Duration of PSA response – D1 of every cycle
• Overall survival – all timepoints until death, lost to FU, or withdrawal of consent
• Incidence of TEAEs, changes in safety parameters, and unacceptable toxicities – all timepoints through 30 days after last dose or initiation of new anticancer treatment
• PLX2853 PK parameters - C1D1, C1D2, C1D15, C2D1, C2D15, C3+D1
• BOR - Every 9 weeks through cycle 10, then every 12 weeks
• DOR – D1 of every cycle until disease progression or death
• Time to first Symptomatic Skeletal-Related Event: - all timepoints through 30 days after last dose or initiation of new anticancer treatment

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

Yes

E.7.1.3.1

Other trial type description

Phase 1 Dose escalation: Evaluate the safety, tolerability, MTD/RP2D, PK

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

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

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 Kingdom

United States

E.8.7

Trial has a data monitoring committee

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

LVLS

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 years

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

110

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)

The Sponsor currently has no plans to provide PLX2853 to study subjects after the close of the study or earlier subject withdrawal. Sponsor will evaluate the appropriateness of continuing to provide
PLX2853 to study subjects after evaluating study data pertaining to the primary efficacy outcome measure and safety. For subjects who are demonstrating a clinical benefit at the end of this study, the possibility of continuing their treatment in this or a roll-over protocol may be considered.

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

2020-09-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-24

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials