## Protocol Section
### Identification Module
**NCT ID:** NCT06425055

**Acronym:** ALPESTRIA-1

**Brief Title:** Vonafexor ALPort Syndrome Efficacy & Safety TRIAl-1 (ALPESTRIA-1)

**Official Title:** Vonafexor Fixed Dose-escalation Safety and Proof-of-concept Study in Patients With at Risk of Progression Alport Syndrome

#### Organization Study ID Info
**ID:** EYP001-208
#### Organization
**Class:** INDUSTRY
**Full Name:** Enyo Pharma
### Status Module
#### Completion Date
**Date:** 2025-10-13

**Type:** ESTIMATED

#### Last Update Post Date
**Date:** 2024-05-23

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-22

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-07-21

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Enyo Pharma

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study is a proof-of-concept trial of vonafexor safety, its effects on kidney function in subjects with at risk of progression Alport syndrome.

**Detailed Description:** This is a multicenter study and several clinical sites and countries will be involved.

This single arm, fixed dose escalation, open-label, non-randomized study will evaluate three dose levels of vonafexor on safety, tolerability and their effect on kidney function and renal biomarkers in 20 patients with AS at risk of progression.

The total duration of study for a participant will be up to 40 weeks and include a screening period, a treatment period of 24 weeks and a follow-up period of 12 weeks.

### Conditions Module

**Conditions:**

- Alport Syndrome

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Single arm fixed dose escalation

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** This is a single arm fixed dose escalation with three dose levels of vonafexor, all QD.

**Intervention Names:**

- Drug: Vonafexor

**Label:** Single arm fixed dose escalation

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Single arm fixed dose escalation

**Description:** * One tablet of a low dose of vonafexor QD from Day 1 to Week 4
* One tablet of a medium dose of vonafexor QD from Week 5 to Week 8
* One tablet of a high dose of vonafexor QD from Week 9 to Week 24

**Name:** Vonafexor

**Other Names:**

- EYP001a

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** To determine the effect of vonafexor on and off treatment on exploratory renal biomarkers

**Measure:** Change in albuminuria

**Time Frame:** During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline

**Description:** To determine the effect of vonafexor on and off treatment on exploratory renal biomarkers

**Measure:** Change in proteinuria

**Time Frame:** During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline

**Description:** To determine the effect of vonafexor on and off treatment on exploratory renal biomarkers

**Measure:** Change in Neutrophil Gelatinase Associated Lipocalin (NGAL)

**Time Frame:** During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline

#### Primary Outcomes

**Description:** To assess the safety and tolerability of vonafexor

**Measure:** Number of Treatment-Emergent Adverse Event (TEAE)

**Time Frame:** From first dose of treatment until 2 weeks after last dose of treatment, i.e assessed up to 26 weeks

#### Secondary Outcomes

**Description:** To determine the on with the off-treatment effect of three dose levels of vonafexor on renal function

**Measure:** Change in eGFR

**Time Frame:** During on-treatment (assessed up to 24 weeks) and off-treatment periods (assessed up to 36 weeks) compared to baseline

**Description:** To determine vonafexor plasma concentrations levels

**Measure:** Vonafexor plasma concentrations

**Time Frame:** During on-treatment period, assessed up to 24 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Signed informed consent (also for legal representatives, as applicable in the US for under eighteen patients).
* Has confirmed diagnosis of Alport syndrome: clinical diagnosis (haematuria, family history, hearing loss, ocular change) OR a kidney biopsy showing glomerular basement membrane abnormalities consistent with AS, AND Genetic confirmation of AS.
* Has eGFR between ≥ 30 and \< 90 ml/min/1.73m2.
* Has increased albuminuria criteria i.e. UACR ≥ 300 mg/g.
* If on an angiotensin converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB), should be on a stable well tolerated treatment during at least the 60 days prior D1.
* If on Sodium-Glucose Transport Protein 2 (SGLT2), should be on stable well tolerated treatment with SGLT2 during at least 60 days prior D1.
* If patient has a history of arterial hypertension, should be on stable anti-hypertensive therapy for at least 60 days prior to D1 and deemed controlled by the investigator at screening and D1.
* Sexually active female subjects of childbearing potential and sexually mature male subjects must use two acceptable effective methods of contraception for the entire duration of the study and for at least 6 weeks after last dose.
* Has negative results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV).
* Is able to understand all study procedures in the informed consent form (ICF) and willing to comply with all aspects of the protocol.

Exclusion Criteria:

* Is an employee of a site, clinical research organization, vendor, or sponsor involved with this study.
* Is pregnant or breastfeeding.
* Has participated in any investigational drug study within 60 days prior to D1.
* Any clinically significant illness within 30 days before D1 or surgical or medical condition (other than Alport syndrome) that could interfere with the subject's study compliance; confound the study results; impact subject safety.
* Any history of active malignancy within the last 1 year before D1.
* Any other condition or circumstance that, in the opinion of the investigator, may make the subject unlikely to complete the study or comply with study procedures and requirements, or may pose a risk to the subject's safety and well-being.
* Has a history of an allergic condition that required the prescription of an emergency epinephrine injection (such as the EpiPen® Auto-Injector).
* Any prohibited co-medications within 30 days prior D1.
* Has ALT or AST above near normal (\>1.5×ULN) at baseline.
* Are at high risk for atherosclerotic cardiovascular disease (ASCVD) risk, with an LDL-C level \> 160 mg/dL (4.15 mmol/L) and subjects at intermediate risk for ASCVD risk, with a LDL-C level \> 190 mg/dL (4.91 mmol/L).
* Has moderate or severe hepatic impairment (Child-Pugh score B or C).
* Is taking CYP3A4/5 inhibitors or inducers.

**Maximum Age:** 55 Years

**Minimum Age:** 16 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** contact@enyopharma.com

**Name:** Isabelle Martin

**Phone:** 00 33 4 37 70 02 44

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Birmingham

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** United States

**Facility:** University of Alabama

**State:** Alabama

**Zip:** 35294

**Location 2:**

**City:** Los Angeles

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** United States

**Facility:** UCLA Health, David Geffen School of Medicine

**State:** California

**Zip:** 90095

**Location 3:**

**City:** Boise

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** United States

**Facility:** Boise Kidney & Hypertension

**State:** Idaho

**Zip:** 83703

**Location 4:**

**City:** Hinsdale

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** United States

**Facility:** NANI Research

**State:** Illinois

**Zip:** 60521

**Location 5:**

**City:** Saint Louis

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** United States

**Facility:** Washington University

**State:** Missouri

**Zip:** 63110

**Location 6:**

**City:** New York

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** United States

**Facility:** Columbia University Medical Center

**State:** New York

**Zip:** 60521

**Location 7:**

**City:** Cleveland

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** United States

**Facility:** Cleveland Clinic Foundation

**State:** Ohio

**Zip:** 44195

**Location 8:**

**City:** Dallas

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** United States

**Facility:** Renal Disease Research Institute

**State:** Texas

**Zip:** 75126

**Location 9:**

**City:** Bordeaux

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** France

**Facility:** CHU De Bordeaux

**Zip:** 33076

**Location 10:**

**City:** Marseille

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** France

**Facility:** Hôpital de la Conception

**Zip:** 13385

**Location 11:**

**City:** Montpellier

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** France

**Facility:** Hopital Lapeyronie

**Zip:** 34090

**Location 12:**

**City:** Paris

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** France

**Facility:** Necker Enfants Malades

**Zip:** 75015

**Location 13:**

**City:** Berlin

**Country:** Germany

**Facility:** Charite Universitatsmedizin Berlin

**Zip:** 10117

**Location 14:**

**City:** Göttingen

**Country:** Germany

**Facility:** University Medicine Goettingen

**Zip:** 37075

**Location 15:**

**City:** Barcelona

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** Spain

**Facility:** Fundacio Puigvert

**Zip:** 08025

**Location 16:**

**City:** El Palmar

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Virgen de la Arrixaca

**Zip:** 30120

**Location 17:**

**City:** Madrid

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** Spain

**Facility:** Fundacion Jimenez Diaz

**Zip:** 28040

**Location 18:**

**City:** Sagunto

**Contacts:**

***Contact 1:***

- **Name:** ENYO Pharma

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital De Sagunto

**Zip:** 46520

### IPD Sharing Statement Module

**Description:** Individual participant data that underline published results might be shared upon request with researchers who provide a methodologically sound proposal and to achieve objectives as set in the approved proposal.

IPD will be shared deidentified and from 3 months and ending 5 years following article publication.

**Info Types:**

- STUDY_PROTOCOL

- SAP

**IPD Sharing:** YES

**Time Frame:** From 3 months and ending 5 years following article publication.

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000014564

- Term: Urogenital Abnormalities

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000009393

- Term: Nephritis

- ID: D000007674

- Term: Kidney Diseases

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000003095

- Term: Collagen Diseases

- ID: D000003240

- Term: Connective Tissue Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M20559

- Name: Disease Progression

- Relevance: LOW

- As Found: Unknown

- ID: M12338

- Name: Nephritis

- Relevance: LOW

- As Found: Unknown

- ID: M12339

- Name: Nephritis, Hereditary

- Relevance: HIGH

- As Found: Alport Syndrome

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M17314

- Name: Urogenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M10698

- Name: Kidney Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15045

- Name: Rheumatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6323

- Name: Collagen Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6464

- Name: Connective Tissue Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T303

- Name: Alport Syndrome

- Relevance: HIGH

- As Found: Alport Syndrome

### Condition Browse Module - Meshes

- ID: D000009394

- Term: Nephritis, Hereditary

- ID: D000013577

- Term: Syndrome

### Misc Info Module

- Version Holder: 2024-05-31
