Clinical Trials Register

Summary
EudraCT Number:	2021-003478-30
Sponsor's Protocol Code Number:	CAAA802A12101
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-03-28
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

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2021-003478-30

A.3

Full title of the trial

SatisfACtion: A Phase I/II, open-label, multi-center study of [225Ac]Ac-PSMA-R2 in men with heavily pre-treated PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) with or without prior 177Lu-labelled PSMA-targeted radioligand therapy.

A.3.1

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

A first in human study of [225Ac]Ac-PSMA-R2 in men with PSMA-positive prostate cancer with or without prior 177Lu-PSMA radioligand therapy for investigation of safety and efficacy.

A.3.2

Name or abbreviated title of the trial where available

SatisfACtion

A.4.1

Sponsor's protocol code number

CAAA802A12101

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma S.A.S
B.5.2	Functional name of contact point	Information&Communication Médicales
B.5.3	Address:
B.5.3.1	Street Address	8/10 rue Henry Sainte Claire Deville, CS 40150
B.5.3.2	Town/ city	Rueil-Malmaison
B.5.3.3	Post code	92563
B.5.3.4	Country	France
B.5.4	Telephone number	+33 1 5547 6600
B.5.5	Fax number	+33 1 5547 6100
B.5.6	E-mail	icm.phfr@novartis.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	[68Ga]Ga-PSMA-R2 30 µg/vial kit for radiopharmaceutical preparation
D.3.2	Product code	AAA502
D.3.4	Pharmaceutical form	Kit for radiopharmaceutical preparation
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.2	Current sponsor code	AAA502
D.3.9.3	Other descriptive name	Gallium (68Ga) PSMA-R2
D.3.9.4	EV Substance Code	SUB203582
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	Yes
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	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	[225Ac]Ac-PSMA-R2 1MBq/mL solution for injection/infusion
D.3.2	Product code	AAA802
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.2	Current sponsor code	AAA802
D.3.9.3	Other descriptive name	AAA802
D.3.9.4	EV Substance Code	SUB233387
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Yes
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

PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC) with or without prior 177Lu-PSMA radioligand therapy.

E.1.1.1

Medical condition in easily understood language

Prostate cancer that has or has not received 177Lu-PSMA radioligand therapy before

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	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10036908
E.1.2	Term	Prostatic neoplasms malignant
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

For Dose Escalation:- To determine the RDE and corresponding regimen for 225Ac-PSMA-R2 monotherapy in PSMA-positive mCRPC in:
Group-1: Participants previously treated with 177Lu-labelled PSMA-targeted RLT (post-177Lu).
Group-2: Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu).

- To charaterize the safety of 225Ac-PSMA-R2 during the first cycle of treatment.

For Dose Expansion:
- To evaluate the anti-tumor activity for 225Ac-PSMA-R2 in post-177Lu and pre-177Lu treatment (naïve) participants.

E.2.2

Secondary objectives of the trial

For Dose Escalation in pre-177Lu and post-177Lu-labelled PSMA-targeted RLTs:
- To characterize the safety and tolerability of 225Ac-PSMA-R2.
- To assess the clinical anti-tumor activity of 225Ac-PSMA-R2.
- To characterize the PK of 225Ac-PSMA-R2 pre-and post-secular equilibrium.

For Dose Expansion in pre-177Lu and post-177Lu-labelled PSMA-targeted RLTs:
- To assess the clinical anti-tumor activity of 225Ac-PSMA-R2.
- To characterize the safety and tolerability of 225Ac-PSMA-R2.
- To characterize the PK of 225Ac-PSMA-R2 pre- and post-secular equilibrium.

For information on exploratory endpoints, please refer to protocol.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

The numbering is reflecting the way it is stated in the protocol. Please refer to the protocol for the complete listing of inclusion criteria.
4. Histological, pathological, and/or cytological confirmation of prostate cancer.
6. Evidence of PSMA-positive disease by 68Ga-PSMA-R2 PET/CT and eligible as determined by central reading.
8. A documented progressive mCRPC based on at least 1 of the following criteria:
- Serum or plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL.
- Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
- Progression of bone disease defined as evaluable disease or new bone lesions(s) by bone scan (2 + 2 PCWG3 criteria, Scher et al 2016).
10. Prior orchiectomy and/or ongoing ARPI, chemotherapy and meet the following criteria in terms of previous 177Lu-labelled PSMA-targeted RLTs in both dose esclation and dose expansion:
- Group 1 (dose escalation) and Group 1 (dose expansion): (post-ARPI, post-CT, post-177Lu): participants must have received previous treatment with 177Lu-labelled PSMA-targeted RLTs.
- Group 2 (dose escalation) and Group 2 (dose expansion): (post ARPI, post-CT, pre-177Lu): participants must have never received previous treatment with 177Lu-labelled PSMA-targeted RLTs.
11. Adequate organ function:
- Bone marrow reserve:
- White blood cell (WBC) count ≥ 3.0 x 109/L -AND- absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
- Platelets ≥ 75 x 109/L.
- Hemoglobin ≥ 8 g/dL (8 g/dL is equivalent to 80 g/L.
- Hepatic function:
- Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert’s Syndrome ≤ 3 x ULN is permitted.
- Alanine aminotransferase (ALT) andaspartate aminotransferase (AST) ≤ 3.0 x ULN OR ≤ 5.0 x ULN for patients with liver metastase.
- Albumin > 3.0 g/dL (3.0 g/dL is equivalent to 30 g/L.
- Renal function:
- Creatinine clearance ≥ 60 mL/min. Note that participants with hydronephrosis or findings indicating blockage of urinary outflow are not eligible.

E.4

Principal exclusion criteria

The numbering is reflecting the way it is stated in the protocol. Please refer to the protocol for the complete listing of exclusion criteria.
1. Previous treatment with any of the following within 6 months of beginning of treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation or previous PSMA-targeted RLT for Group 2 (dose escalation) and for Group 2 (dose expansion).
2. Any other investigational agents within 28 days of the anticipated C1D1 of 225Ac-PSMA-R2 therapy.
5. Uncontrolled pain or incompatibility that may result in participant’s lack of ability to comply with imaging procedures.
10. Uncontrolled cardiovascular history, defined as:
• Congestive heart failure (New York Heart Association [NYHA] II, III, IV.
• Mean resting corrected QT interval (QTc) > 470 millisecond (msec), obtained from 3 ECGs recordings, using the screening clinic ECG machine-derived QTc value.
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 msec).
• Any factor increasing the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
11. Diagnosis of other malignancies expected to alter life expectancy or may interfere with disease assessment. Prior history of malignancy who have been disease free for more than 3 years are eligible.

E.5 End points

E.5.1

Primary end point(s)

Endpoints for Primary Objectives for Dose Escalation:
- Incidence and severity of DLTs during the first cycle of treatment.
- Incidence and severity of AEs and SAEs including changes in laboratory values, ECGs and vital signs during the first cycle of treatment.

Endpoints for Primary Objectives for Dose Expansion:
-ORR per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and (PSA50) response rate.

E.5.1.1

Timepoint(s) of evaluation of this end point

Every 8 weeks (± 1 week) as long as participant are receiving the treatment and then every 12 weeks (± 1 week) through the end of treatment visit

E.5.2

Secondary end point(s)

Endpoints for Secondary Objectives for Dose Escalation:
- Incidence and severity of AEs and SAEs including changes in laboratory values, ECGs and vital signs. 12-lead ECGs in triplicates.
- Frequency of dose interruptions, reductions, discontinuations, and dose intensity by treatment.
- ORR, Disease Control Rate (DCR), Best Overall Response (BOR), radiographic Progression Free Survival (rPFS), OS and Duration of Response (DoR) per PCWG3-modified RECIST v1.1 by Investigator assessment, Time to first Symptomatic Skeletal Event (SSE), biochemical responses as measured by PSA, Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) and change from baseline [68Ga]Ga-PSMA-R2 PET SUV.
- Radioactivity measurements in blood during the first cycle of treatment and derived PK parameters (i.e. AUC, Cmax, CL, Tmax, Vz, T1/2) of 225Ac-PSMA-R2 at different measurement times (pre- and post-secular equilibrium).

Endpoints for Secondary Objectives for Dose Expansion:
- DCR, BOR, rPFS, OS and DoR per PCWG3-modified RECIST v1.1, Time to first SSE, biochemical responses as measured by PSA, ALP, LDH and change from baseline [68Ga]Ga-PSMA-R2 PET SUV.
- Incidence and severity of AEs and serious adverse events (SAEs) including changes in laboratory values, electrocardiograms (ECGs) and vital signs.12-lead ECGs in triplicates during the first cycle of treatment.
- Frequency of dose interruptions, reductions, and dose intensity, by treatment.
- Radioactivity measurements in blood during Cycle 1 and derived PK parameters (i.e. AUC, Cmax, CL, Tmax, Vz, T1/2) of 225Ac-PSMA-R2 at different measurement times (pre- and post-secular equilibrium).

E.5.2.1

Timepoint(s) of evaluation of this end point

Every 8 weeks (± 1 week) as long as participant are receiving the treatment and then every 12 weeks (± 1 week) through the end of treatment visit

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

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.1.1

First administration to humans

Yes

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)

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.8.3

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

The end of study is defined as the earliest occurrence of one of the following: All participants have died, completed the surival follow-up, discontinued from the study, withdrawn consent, or are lost to follow-up.

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

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:

150

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.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)

This is a first in human (FIH) study investigating 225Ac-PSMA-R2 radioligand therapy (RLT) with the aim to establish a Recommended Phase II Dose (RDE) for Dose Expansion. There is no plan for further treatment with RLT after participation at this time. Subjects will continue to be treated with best standard of care (BsC).

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

2022-05-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-08-15

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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