Trial no.:	PACTR202301768862135	Date of Registration:	16/01/2023
Trial Status:	Registered in accordance with WHO and ICMJE standards

TRIAL DESCRIPTION

Public title

Phase 2/3 Adaptive Study of VX-147 in Adult and Pediatric Subjects With APOL1- Mediated Proteinuric Kidney Disease (AMPLITUDE)

Official scientific title

A Phase 2/3 Adaptive, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of VX-147 in Adult and Pediatric Subjects With APOL1-mediated Proteinuric Kidney Disease (AMPLITUDE)

Brief summary describing the background and objectives of the trial

The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of VX-147 in adult and pediatric participants with apolipoprotein L1 (APOL1)-mediated proteinuric kidney disease. The primary and secondary objectives of the trial are listed below. Primary Objectives: • To evaluate the efficacy of VX-147 to reduce proteinuria • To evaluate the efficacy of VX-147 on renal function as measured by eGFR slope Secondary Objectives: • To evaluate the efficacy of VX-147 to decrease the risk of the composite clinical outcome • To evaluate the safety and tolerability of VX-147 • To identify the optimal dose from Phase 2 to carry forward to Phase 3 • To characterize the plasma pharmacokinetics (PK) of VX-147 • To evaluate the acceptability of VX-147 in pediatric subjects

Type of trial

RCT

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

AMPLITUDE

Disease(s) or condition(s) being studied

Kidney Disease

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

Purpose of the trial

Treatment: Drugs

Anticipated trial start date

31/03/2023

Actual trial start date

21/06/2023

Anticipated date of last follow up

29/05/2026

Actual Last follow-up date

Anticipated target sample size (number of participants)

150

Actual target sample size (number of participants)

Recruitment status

Recruiting

Publication URL

Secondary Ids	Issuing authority/Trial register
VX21 147 301	Vertex Pharmaceuticals Incorporated
NCT05312879	ClinicalTrials.gov
2021 004762 35	EudraCT

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
Parallel: different groups receive different interventions at same time during study	Randomised	Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification	Central randomisation by phone/fax	Masking/blinding used	Care giver/Provider,Outcome Assessors,Participants

INTERVENTIONS
Intervention type	Intervention name	Dose	Duration	Intervention description	Group size	Nature of control
Experimental Group	Phase 2 VX 147	Participants will be randomized to receive different dose levels of VX-147	Approximately 2 years (96 weeks) after enrollment of the last study subject	Tablets for oral administration.	4
Control Group	Phase 2 Placebo	Placebo matched to VX 147. Placebo subjects receive standard of care.	Approximately 2 years (96 weeks) after enrollment of the last study subject	Tablets for oral administration.	4	Placebo
Experimental Group	Phase 3 VX 147	Participants will receive VX-147 with the dose to be based on the outcome of Phase 2.	Approximately 2 years (96 weeks) after enrollment of the last study subject	Tablets for oral administration.	21
Control Group	Phase 3 Placebo	Participants will receive placebo matched to VX-147. Placebo subjects receive standard of care.	Approximately 2 years (96 weeks) after enrollment of the last study subject	Tablets for oral administration.	21	Placebo

ELIGIBILITY CRITERIA
List inclusion criteria	List exclusion criteria	Age Category	Minimum age	Maximum age	Gender
Key Inclusion criteria: • APOL1 genotype of G1/G1, G2/G2, or G1/G2 • Proteinuric kidney disease	Key Exclusion Criteria: • Solid organ or bone marrow transplant • Uncontrolled hypertension • Diagnosis of diabetes mellitus • Known underlying cause of kidney disease including but not limited to sickle cell disease Other protocol defined Inclusion/Exclusion criteria apply.	Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Aged: 65 Year(s)-79 Year(s),Middle Aged: 45 Year(s)-64 Year(s)	12 Year(s)	65 Year(s)	Both

ETHICS APPROVAL

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

20/04/2023

Komfo Anokye Teaching Hospital Institutional Review Board

Ethics Committee Address
Street address	City	Postal code	Country
P.O. Box 1934	Kumasi	1934	Ghana

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

22/05/2023

Korle Bu Teaching Hospital Institutional Review Board

Ethics Committee Address
Street address	City	Postal code	Country
Research Office, Medical Directorate Central Admin Block, Korle Bu Teaching Hospital	Accra	77	Ghana

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

09/10/2023

Ghana Health Service Ethics Research Committee

Ethics Committee Address
Street address	City	Postal code	Country
P.O. Box MB 190	Accra	190	Ghana

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

02/03/2023

Committee on Human Research Publication and Ethics

Ethics Committee Address
Street address	City	Postal code	Country
Accra Road	Kumasi, Ashanti Region	1934	Ghana

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

06/12/2023

Noguchi Memorial Institute for Medical Research Institutional Review Board

Ethics Committee Address
Street address	City	Postal code	Country
Noguchi Road	Accra	25	Ghana

OUTCOMES
Type of outcome	Outcome	Timepoint(s) at which outcome measured
Primary Outcome	Percent Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) at Week 48 (Assessed at the Week 48 Interim Analysis)	From Baseline up to Week 48
Primary Outcome	Estimated Glomerular Filtration Rate (eGFR) Slope Assessed at the Week 48 Interim Analysis	From Baseline to at least week 48
Primary Outcome	eGFR Slope Assessed at Study Completion	From Baseline Through Study Completion - Approximately 2 Years After the Last Participant Enrolls
Secondary Outcome	Time to composite clinical outcome of a sustained decline of ≥30% from baseline in estimated glomerular filtration rate (eGFR), the onset of ESKD (i.e., maintenance dialysis for ≥28 days, kidney transplantation, or a sustained eGFR of <15 mL/min/1.73 m2), or death. (Sustained is defined as confirmation by a second measurement after ≥28 days) (assessed at the final analysis).	Baseline Through Study Completion - Approximately 2 Years After the Last Participant Enrolls
Secondary Outcome	Safety and Tolerability as Assessed by Number of Participants With Adverse events (AEs) and Serious Adverse Events (SAEs)	Day 1 Through Study Completion - Approximately 2 Years After the Last Participant Enrolls
Secondary Outcome	Acceptability Tablet Formulation of VX-147 in Pediatric Participants using the Convenience Domain of the Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4	Day 1 and Week 48
Secondary Outcome	Plasma pharmacokinetics (PK) parameters of VX-147	Day 1, Weeks 4, 8, 12, 16, 24, 32 and 40

RECRUITMENT CENTRES
Name of recruitment centre	Street address	City	Postal code	Country
Department of Nephrology Komfo Anokye Teaching Hospital	Okomfo Anokye Road	Kumasi	1934	Ghana
Korle Bu Teaching Hospital Department of Medicine	Guggisberg Avenue	Accra		Ghana
The Bank Hospital	Block F6 Shippi Road, Cantonments	Accra		Ghana
Nigerian Institute of Medical Research	Nigerian Institute of Medical Research, 6 Edmund Cres, Yaba	Lagos	101245	Nigeria
University of Nigeria Teaching Hospital	University of Nigeria Center of Excellence for Clinical Trials, University of Nigeria Teaching Hospital, Ituku-Ozalla	Enugu		Nigeria
Lagos University Teaching Hospital	Lagos University Teaching Hospital , Ishaga Road, Surulere	Lagos	102215	Nigeria
University College Hospital	University College Hospital, Queen Elizabeth II road, Orita Mefa	Ibadan	200285	Nigeria
Lagos State University Teaching Hospital	Lagos State University Teaching Hospital - LASUTH, 1-5 Oba Akinjobi Way, Street, Ikeja	Lagos	101233	Nigeria

FUNDING SOURCES
Name of source	Street address	City	Postal code	Country
Vertex Pharmaceuticals Incorporated	50 Northern Avenue	Boston	02210-186	United States of America

SPONSORS
Sponsor level	Name	Street address	City	Postal code	Country	Nature of sponsor
Primary Sponsor	Vertex Pharmaceuticals Incorporated	50 Northern Avenue	Boston	02210-186	United States of America	Commercial Sector/Industry

COLLABORATORS
Name	Street address	City	Postal code	Country

CONTACT PEOPLE
Role	Name	Email	Phone	Street address
Public Enquiries	Global Medical Information Global Medical Information	vertexmedicalinfo@vrtx.com	0035317617299	2 Kingdom Street
City	Postal code	Country	Position/Affiliation
London	W2 6BD	United Kingdom	Public Enquiries
Role	Name	Email	Phone	Street address
Scientific Enquiries	Global Medical Information Global Medical Information	vertexmedicalinfo@vrtx.com	0035317617299	2 Kingdom Street
City	Postal code	Country	Position/Affiliation
London	W2 6BD	United Kingdom	Scientific Enquiries
Role	Name	Email	Phone	Street address
Principal Investigator	Dwomoa Adu	dwoms15@gmail.com	+233302674066	Department of Medicine Korle Bu Teaching Hospital, Guggisberg Avenue
City	Postal code	Country	Position/Affiliation
Accra		Ghana	Principal Investigator

REPORTING
Share IPD	Description	Additional Document Types	Sharing Time Frame	Key Access Criteria
Yes	Individual patient data can be obtained by qualified researchers who submit a complete research proposal and pre-specified analysis plan. Vertex is committed to advancing medical science and improving patient health through the responsible sharing of clinical trial data with qualified researchers. Proposals for the use of these data will be reviewed by a scientific board and approvals are at Vertex’s discretion and will be dependent on the nature of the request, the merit of the research proposed, and the intended use of the data. Only data elements needed to achieve the specific scientific aims of the proposal as outlined in the pre-specified analysis plan will be provided. Data will be anonymized in accordance with data privacy laws.	Statistical Analysis Plan,Study Protocol	After regulatory approval is achieved in all planned countries or regions, individual patient data can be obtained by qualified researchers who submit a complete research proposal and pre-specified analysis plan to conduct post-hoc analyses. When the submitted proposal is approved by the Scientific Review Board, data will be made available once a Data Sharing Agreement is in place.	Researchers are granted access to data and documents via a secure third-party website. Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing
URL	Results Available	Results Summary	Result Posting Date	First Journal Publication Date
https://www.vrtx.com/our-science/clinical-trials-data-sharing	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

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