Trial no.:	DOH-27-112024-4693	Date of Approval:	08/11/2024
Trial Status:	Approved

TRIAL DESCRIPTION

Public title

RHN001-DX/TX in men with PSMA-positive prostate cancer

Official scientific title

A Phase I/II study of RHN001-DX/TX in men with PSMA-positive prostate cancer post adjuvant androgen deprivation therapy and/or taxane-based chemotherapy

Brief summary describing the background and objectives of the trial

As of 2020 the global incidence of prostate cancer was over 1.4 million, with over 375,000 deaths. When compared to 2012 figures, an upward trend was seen. Various peptide receptor radioligand therapies have been explored and some have been FDA approved.Despite this, the access to [177Lu] Lu-PSMA-617 and PET/CT imaging facilities remains a challenge in low-income countries. These are costly and not readily available. In the low-income countries without access to PET/CT imaging, [99mTc]Tc is readily available making it a feasible option for imaging with the widely available gamma cameras. Therefore, development of a cheaper and therapeutic agent whose radionuclide has similar chemistry to that of [99mTc]Tc may address this need. [188Re]Re is the ideal candidate since it has similar chemical properties with that of [99mTc]Tc it can label similar compounds with ease. One of the compounds that has been designed to suit this role is the PSMA targeting RHN001 which can be labelled with both [99mTc]Tc and [188Re]Re for imaging and therapy respectively. Primary objective: • To identify the recommended Phase 2 dose (RP2D), and schedule of administration for RHN001-TX in men with progressive PSMA-positive prostate cancer who have had neoadjuvant androgen deprivation therapy and/or taxane-based chemotherapy. Secondary objectives: • Assess the overall safety including the dosimetry of RHN001-TX in men with PSMA-positive prostate cancer. • Assess the safety including the dosimetry of RHN001-DX in men with prostate cancer. • Assess health-related quality of life: Functional Assessment of Cancer Therapy- Prostate (FACT-P), Brief Pain Inventory-Short Form (BPI-SF), EQ-5D-5L and XeQOLS xerostomia questionnaire.

Type of trial

Non-Randomised

Acronym (If the trial has an acronym then please provide)

Disease(s) or condition(s) being studied

Cancer

Sub-Disease(s) or condition(s) being studied

Purpose of the trial

Treatment: Drugs

Anticipated trial start date

28/02/2025

Actual trial start date

27/02/2025

Anticipated date of last follow up

28/02/2027

Actual Last follow-up date

Anticipated target sample size (number of participants)

37

Actual target sample size (number of participants)

Recruitment status

Recruiting

Publication URL

https://clinicaltrials.gov

Secondary Ids	Issuing authority/Trial register
RHN001-100	Sponsor

STUDY DESIGN
Intervention assignment	Allocation to intervention	If randomised, describe how the allocation sequence was generated	Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms	Masking	If masking / blinding was used
Single Group	Non-randomised			Open-label(Masking Not Used)

INTERVENTIONS
Intervention type	Intervention name	Dose	Duration	Intervention description	Group size	Nature of control
Experimental Group	RHN001	Patients will receive RHN001-DX for diagnostic purposes and RHN001-TX for therapeutic purposes. RHN001-DX with whole-body imaging will be done prior to the study and before subsequent cycles of RHN001-TX. The RHN001-TX will be given for a maximum of 4 cycles for patient receiving eMTD (50%, 65% and 75%); whereas 3-cycles in patients receiving 100% of eMTD. Cohort A: Dosimetry for RHN001-DX RHN001-DX containing 10µg of the peptide at a specific activity (MBq) will be injected intravenously. Activity will be adjusted for patient weight. Cohort B: Dosimetry for RHN001-TX RHN001-TX containing 10µg of the peptide at a specific activity (MBq) will be injected intravenously. Activity will be adjusted for patient weight. Cohort C: Escalation study with RHN001-TX Administered activity will be based in the estimated maximum tolerable dose(eMTD). These patients will be divided into 4-groups with administration of 50%, 65%, 75% and 100% eMTD with activities, number of cycles and cycle interval.	Cohort A and B once off administration Cohort C up to a maximum of 3-4 cycles every 4-6 weeks depending on the group.	Study eligible patients will be assigned to one of three cohorts. • Cohort A- RHN001-DX dosimetry cohort: Dosimetry of diagnostic use of RHN001-DX. The required number of patients will be five(n=10-20). • Cohort B- RHN001-TX dosimetry cohort: Treatment of men with metastatic PSMA-positive prostate cancer on RHN001-DX whole body imaging with or without therapies. The required number of patients will be five(n=5). • Cohort C: Escalation study with RHN001-TX Treatment of men with mCRPC PSMA-positive on RHN001-DX whole body imaging post adjuvant androgen deprivation therapy and/or taxane based chemotherapy. These patients will be divided into 4-groups with administration of different % of the eMTD The number of patients per group in this cohort of patients will be three(n=3)	37
Control Group	No control group	Not applicable	Not applicable	Not applicable.	0	Uncontrolled

ELIGIBILITY CRITERIA
List inclusion criteria	List exclusion criteria	Age Category	Minimum age	Maximum age	Gender
Inclusion Criteria: 1) Patient must have the ability to understand and sign an approved ICF. 2) Patient must have the ability to understand and comply with all protocol requirements. 3) Patients must be ≥18 years of age. 4) Patients must have an ECOG performance status of 0 to 2. 5) Patient must have had histological, pathological and/or cytological confirmation of prostate cancer. 6) Patients with measurable disease on CT as per PCWG3 recommendations. 7) Patient must have a positive RHN001-DX whole-body imaging performed within 14-days of study entry 8) Patients must have recovered or stabilized to ≤Grade 2 or baseline from all clinically significant toxicities related to prior prostate cancer therapy. 9) Applicable to Cohort B and C patients only. Determination of disease progression on treatment prior to enrolment. 10) Applicable to Cohort B and C patients only. Patients must have adequate organ function 11) Known HIV-positive patients who are healthy and have a low risk of AIDS-related outcomes are eligible. 12) For patients who have partners of childbearing potential, Patients must use a method of birth control 13) RHN001-DX dosimetry cohort (Cohort A only): The patients must be newly diagnosed and have low-volume disease. 14) RHN001-TX dosimetry cohort (Cohort B only): The patients must be able to tolerate serial imaging preferably ECOG 0.	1) Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, radium-223 or hemi-body irradiation (Lu-177 or Ac-225 PSMA). 2) Any investigational agents within 28 days of study enrolment. 3) Known hypersensitivity to the components of the study for imaging and therapy and the respective analogues. 4) Other concurrent cytotoxic chemotherapy targeted therapy, biologic agents, immunotherapy, radioligand therapy, or investigational therapy. 5) Transfusion for the purposes of eligibility into the study. 6) Patients with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and are not neurologically impaired. 7) Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression. 8) Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. 9) Patients with a prior history of malignancy which may interfere with disease assessment who have been disease-free for more than 3 years are eligible.	Adult: 19 Year(s)-105 Year(s)	18 Year(s)	100 Year(s)	Male

APPROVALS

Has the study received appropriate ethics committee approval

Date the study will be submitted for approval

Date of approval

Name of the ethics committee

Yes

21/07/2024

SAHPRA

Ethics Committee Address
Street address	City	Postal code	Country
Building A, Loftus Park 2nd Floor, Kirkness Street Arcadia	Pretoria	0083	South Africa

Has the study received appropriate ethics committee approval

Date the study will be submitted for approval

Date of approval

Name of the ethics committee

Yes

04/09/2024

University of Pretoria Faculty of Health Sciences Research Ethics Committee

Ethics Committee Address
Street address	City	Postal code	Country
University of Pretoria Faculty of Health Sciences Tswelopele Building, Level 4, Rooms 4-59 and 4-60 (opposite the BMS Building), 9 Bophelo Road, Gezina, Pretoria	Pretoria	0001	South Africa

OUTCOMES
Type of outcome	Outcome	Timepoint(s) at which outcome measured
Primary Outcome	To identify the recommended Phase 2 dose (RP2D), and schedule of administration for RHN001-TX in men with progressive PSMA-positive prostate cancer who have had neoadjuvant androgen deprivation therapy and/or taxane-based chemotherapy.	End of Study
Secondary Outcome	Assess the overall safety including the dosimetry of RHN001-TX in men with PSMA-positive prostate cancer.	End of Study
Secondary Outcome	Assess the safety including the dosimetry of RHN001-DX in men with prostate cancer.	End of Study
Secondary Outcome	Assess health-related quality of life: Functional Assessment of Cancer Therapy- Prostate (FACT-P), Brief Pain Inventory-Short Form (BPI-SF), EQ-5D-5L and XeQOLS xerostomia questionnaire.	End of Study

RECRUITMENT CENTRES
Name of recruitment centre	Street address	City	Postal code	Country
Prof Mike Sathekge Department of Nuclear Medicine Steve Biko Academic Hospital University of Pretoria	Corner of Steve Biko and Malan Stre	Pretoria	0001	South Africa

FUNDING SOURCES
Name of source	Street address	City	Postal code	Country
Nuclear Medicine Research Infrastructure NuMeRi	Steve Biko Hospital, Corner of Steve Biko Road and Malan Street, Capital Park	Pretoria	0001	South Africa

SPONSORS
Sponsor level	Name	Street address	City	Postal code	Country	Nature of sponsor
Primary Sponsor	Nuclear Medicine Research Infrastructure	Room 51312 Level 5 Bridge A, Cnr Steve Biko and Malan Street, Capital Park	Pretoria	0001	South Africa	Non-profit Research Company

COLLABORATORS
Name	Street address	City	Postal code	Country
Rhine Pharma GmbH	Schweriner Strasse 50a	Dresden	01067	Germany

CONTACT PEOPLE
Role	Name	Email	Phone	Street address
Principal Investigator	Mike Sathekge	mike.sathekge@up.ac.za	0027834617653	Steve Biko Academic Hospital
City	Postal code	Country	Position/Affiliation
Pretoria	0001	South Africa	Sponsor
Role	Name	Email	Phone	Street address
Scientific Enquiries	Honest Ndlovu	honest.ndlovu@sanumeri.co.za	0027816032807	Steve Biko Academic Hospital
City	Postal code	Country	Position/Affiliation
Pretoria	0001	South Africa	Sponsor
Role	Name	Email	Phone	Street address
Public Enquiries	Tertia De Bruin	tertia.debruin@abx-cro.com	0027832279896	101, Big Bay Office Park, Beach Estate Boulevard, Big Bay
City	Postal code	Country	Position/Affiliation
Cape Town	7441	South Africa	CRO

REPORTING
Share IPD	Description	Additional Document Types	Sharing Time Frame	Key Access Criteria
Yes	External qualified researchers may request IPD for this study after the study is completed or during the study for inspection. As per the informed consent "Any information obtained in connection with this clinical trial that can identify you will remain confidential. You will be identified by a trial code/participant number. Your health records and any information obtained during the research project are subject to inspection (for verifying the procedures and the data) by the relevant authorities and authorised representatives of the Sponsor. It is anticipated that the results of this clinical trial will be published and/or presented in a variety of forums. In any publication and/or presentation, information will be provided in such a way that you cannot be identified, except with your permission.	Informed Consent Form,Study Protocol	As per informed consent "The trial (study) doctor will keep the list matching your participant trial code/participant number with your medical and identifying information for at least 15 years after the end of the trial or for at least 2 years after the investigational product is approved for sale by relevant regulatory agencies (whichever comes later).	A secured external system with username and password.
URL	Results Available	Results Summary	Result Posting Date	First Journal Publication Date
	No
Result Upload 1:	Result Upload 2:	Result Upload 3:	Result Upload 4:	Result Upload 5:

Result URL Hyperlinks	Link To Protocol
Result URL Hyperlinks

Changes to trial information
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Anticipated trial start date	11/02/2025	Updated information	01 Jan 2025	28 Feb 2025
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Actual trial start date	05/03/2025	Updated information		27 Feb 2025
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Anticipated date of last follow up	11/02/2025	Updated information	31 Dec 2026	28 Feb 2027
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Target no of participants	11/02/2025	Updated information	22	27
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Target no of participants	01/12/2025	Updated per approved Protocol V5.0	27	37
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Trial Information	Recruitment status	05/03/2025	Updated information.	Not yet recruiting	Recruiting
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Study Design	Intervention assignment	04/11/2024	Patients will not be randomized. The patients will receive similar IMP at different doses in different stages of the clinical trial. (Dose escalation)	Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously	Single Group
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Eligibility	Sex	01/12/2025	Entry error. Only male patients with prostate cancer	Both	Male
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Eligibility	Inclusion criteria	01/12/2025	Updated bawed On approved Protocol V5.0	Inclusion Criteria: 1) Patient must have the ability to understand and sign an approved ICF. 2) Patient must have the ability to understand and comply with all protocol requirements. 3) Patients must be =18 years of age. 4) Patients must have an ECOG performance status of 0 to 2. 5) Patient must have had histological, pathological and/or cytological confirmation of prostate cancer. 6) Patients with measurable disease on CT as per PCWG3 recommendations. 7) Patient must have a positive RHN001-DX whole-body imaging performed within 14-days of study entry 8) Patients must have recovered or stabilized to =Grade 2 or baseline from all clinically significant toxicities related to prior prostate cancer therapy. 9) Determination of disease progression on treatment prior to enrolment. 10) Patients must have adequate organ function 11) Known HIV-positive patients who are healthy and have a low risk of AIDS-related outcomes are eligible. 12) For patients who have partners of childbearing potential, Patients must use a method of birth control 13) RHN001-DX dosimetry cohort: The patients must be newly diagnosed and have low-volume disease. 14) RHN001-TX dosimetry cohort: The patients must be able to tolerate serial imaging preferably ECOG 0.	Inclusion Criteria: 1) Patient must have the ability to understand and sign an approved ICF. 2) Patient must have the ability to understand and comply with all protocol requirements. 3) Patients must be =18 years of age. 4) Patients must have an ECOG performance status of 0 to 2. 5) Patient must have had histological, pathological and/or cytological confirmation of prostate cancer. 6) Patients with measurable disease on CT as per PCWG3 recommendations. 7) Patient must have a positive RHN001-DX whole-body imaging performed within 14-days of study entry 8) Patients must have recovered or stabilized to =Grade 2 or baseline from all clinically significant toxicities related to prior prostate cancer therapy. 9) Applicable to Cohort B and C patients only. Determination of disease progression on treatment prior to enrolment. 10) Applicable to Cohort B and C patients only. Patients must have adequate organ function 11) Known HIV-positive patients who are healthy and have a low risk of AIDS-related outcomes are eligible. 12) For patients who have partners of childbearing potential, Patients must use a method of birth control 13) RHN001-DX dosimetry cohort (Cohort A only): The patients must be newly diagnosed and have low-volume disease. 14) RHN001-TX dosimetry cohort (Cohort B only): The patients must be able to tolerate serial imaging preferably ECOG 0.
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Intervention	Intervention List	01/12/2025	Updated per approved Protocol V5.0	Experimental Group, RHN001, Patients will receive RHN001-DX for diagnostic purposes and RHN001-TX for therapeutic purposes. RHN001-DX with whole-body imaging will be done prior to the study and before subsequent cycles of RHN001-TX. The RHN001-TX will be given for a maximum of 4 cycles for patient receiving eMTD (50%, 65% and 75%); whereas 3-cycles in patients receiving 100% of eMTD. Cohort A: Dosimetry for RHN001-DX RHN001-DX containing 10µg of the peptide at a specific activity (MBq) will be injected intravenously. Activity will be adjusted for patient weight. Cohort B: Dosimetry for RHN001-TX RHN001-TX containing 10µg of the peptide at a specific activity (MBq) will be injected intravenously. Activity will be adjusted for patient weight. Cohort C: Escalation study with RHN001-TX Administered activity will be based in the estimated maximum tolerable dose(eMTD). These patients will be divided into 4-groups with administration of 50%, 65%, 75% and 100% eMTD with activities, number of cycles and cycle interval. , Cohort A and B once off administration Cohort C up to a maximum of 3-4 cycles every 4-6 weeks depending on the group., Study eligible patients will be assigned to one of three cohorts. • Cohort A- RHN001-DX dosimetry cohort: Dosimetry of diagnostic use of RHN001-DX. The required number of patients will be five(n=5). • Cohort B- RHN001-TX dosimetry cohort: Treatment of men with metastatic PSMA-positive prostate cancer on RHN001-DX whole body imaging with or without therapies. The required number of patients will be five(n=5). • Cohort C: Escalation study with RHN001-TX Treatment of men with mCRPC PSMA-positive on RHN001-DX whole body imaging post adjuvant androgen deprivation therapy and/or taxane based chemotherapy. These patients will be divided into 4-groups with administration of different % of the eMTD The number of patients per group in this cohort of patients will be three(n=3) , 22,	Experimental Group, RHN001, Patients will receive RHN001-DX for diagnostic purposes and RHN001-TX for therapeutic purposes. RHN001-DX with whole-body imaging will be done prior to the study and before subsequent cycles of RHN001-TX. The RHN001-TX will be given for a maximum of 4 cycles for patient receiving eMTD (50%, 65% and 75%); whereas 3-cycles in patients receiving 100% of eMTD. Cohort A: Dosimetry for RHN001-DX RHN001-DX containing 10µg of the peptide at a specific activity (MBq) will be injected intravenously. Activity will be adjusted for patient weight. Cohort B: Dosimetry for RHN001-TX RHN001-TX containing 10µg of the peptide at a specific activity (MBq) will be injected intravenously. Activity will be adjusted for patient weight. Cohort C: Escalation study with RHN001-TX Administered activity will be based in the estimated maximum tolerable dose(eMTD). These patients will be divided into 4-groups with administration of 50%, 65%, 75% and 100% eMTD with activities, number of cycles and cycle interval. , Cohort A and B once off administration Cohort C up to a maximum of 3-4 cycles every 4-6 weeks depending on the group., Study eligible patients will be assigned to one of three cohorts. • Cohort A- RHN001-DX dosimetry cohort: Dosimetry of diagnostic use of RHN001-DX. The required number of patients will be five(n=10-20). • Cohort B- RHN001-TX dosimetry cohort: Treatment of men with metastatic PSMA-positive prostate cancer on RHN001-DX whole body imaging with or without therapies. The required number of patients will be five(n=5). • Cohort C: Escalation study with RHN001-TX Treatment of men with mCRPC PSMA-positive on RHN001-DX whole body imaging post adjuvant androgen deprivation therapy and/or taxane based chemotherapy. These patients will be divided into 4-groups with administration of different % of the eMTD The number of patients per group in this cohort of patients will be three(n=3) , 37,
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Collaborators	Collaborators List	10/02/2025	Updated Information	ABXCRO Advanced Pharmacuetical Services Forschungsgesellschaft mbH, Schossergasse 19, Dresden, 01067, Germany	Rhine Pharma GmbH, Schweriner Strasse 50a , Dresden, 01067, Germany
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Reporting	IPD description	06/11/2024	Updated upon request from SAMRC	IPD sharing statement will be provided within 12 months of study completion date. The results of this trial will be publicly disclose or submit for publication as an article, manuscript, abstract, poster, presentation, or other material, in written or electronic form.	External qualified researchers may request IPD for this study after the study is completed or during the study for inspection. As per the informed consent "Any information obtained in connection with this clinical trial that can identify you will remain confidential. You will be identified by a trial code/participant number. Your health records and any information obtained during the research project are subject to inspection (for verifying the procedures and the data) by the relevant authorities and authorised representatives of the Sponsor, the institution relevant to this Participant Information Sheet, Steve Biko Academic Hospital (SBAH), or as required by law (including SAHPRA, National Health Research Ethics Council (NHREC), relevant Independent Ethics Committee (IEC) and/or other regulatory authorities. It is anticipated that the results of this clinical trial will be published and/or presented in a variety of forums. In any publication and/or presentation, information will be provided in such a way that you cannot be identified, except with your permission.
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Reporting	IPD description	06/11/2024	Updated upon request from SAMRC	External qualified researchers may request IPD for this study after the study is completed or during the study for inspection. As per the informed consent "Any information obtained in connection with this clinical trial that can identify you will remain confidential. You will be identified by a trial code/participant number. Your health records and any information obtained during the research project are subject to inspection (for verifying the procedures and the data) by the relevant authorities and authorised representatives of the Sponsor, the institution relevant to this Participant Information Sheet, Steve Biko Academic Hospital (SBAH), or as required by law (including SAHPRA, National Health Research Ethics Council (NHREC), relevant Independent Ethics Committee (IEC) and/or other regulatory authorities. It is anticipated that the results of this clinical trial will be published and/or presented in a variety of forums. In any publication and/or presentation, information will be provided in such a way that you cannot be identified, except with your permission.	External qualified researchers may request IPD for this study after the study is completed or during the study for inspection. As per the informed consent "Any information obtained in connection with this clinical trial that can identify you will remain confidential. You will be identified by a trial code/participant number. Your health records and any information obtained during the research project are subject to inspection (for verifying the procedures and the data) by the relevant authorities and authorised representatives of the Sponsor. It is anticipated that the results of this clinical trial will be published and/or presented in a variety of forums. In any publication and/or presentation, information will be provided in such a way that you cannot be identified, except with your permission.
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Reporting	IPD-Sharing time frame	06/11/2024	Timeframe updated as per ICF	Within 12 months of study completion date if required by law.	As per informed consent "The trial (study) doctor will keep the list matching your participant trial code/participant number with your medical and identifying information for at least 15 years after the end of the trial or for at least 2 years after the investigational product is approved for sale by relevant regulatory agencies (whichever comes later).
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Reporting	Key access criteria	06/11/2024	Updated information	To be shared if required by law.	A secured external system with username and password.
Section Name	Field Name	Date	Reason	Old Value	Updated Value
Reporting	IPD URL	06/11/2024	Updated information	www.clinicaltrials.gov

South African National Clinical Trials Registry