## Protocol Section
### Identification Module
**NCT ID:** NCT06431776

**Brief Title:** Inhaled Molgramostim in Pediatric Participants With Autoimmune Pulmonary Alveolar Proteinosis (aPAP).

**Official Title:** An Open-label, Multicenter Clinical Study to Evaluate the Efficacy and Safety of Inhaled Molgramostim in Pediatric Participants With Autoimmune Pulmonary Alveolar Proteinosis (aPAP).

#### Organization Study ID Info
**ID:** SAV006-04
#### Organization
**Class:** INDUSTRY
**Full Name:** Savara Inc.
### Status Module
#### Completion Date
**Date:** 2027-08

**Type:** ESTIMATED

#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

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

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-08

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-22
**Study First Submit QC Date:** 2024-05-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Savara Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The goal of this open-label study is to study molgramostim as a treatment for autoimmune pulmonary alveolar proteinosis (aPAP) in pediatric patients between age 6 and 18. The main questions it aims to answer are:

The effect of molgramostim on breathing tests and activity in pediatric patients with aPAP and the safety of molgramostim in pediatric patients with aPAP.

This is an open-label study: all participants will receive treatment with molgramostim.

Patients will:

* Take molgramostim once daily via nebulizer every day for 12 months.
* Visit the clinic approximately every 12 weeks for checkups and tests.
* Keep a diary of any oxygen use.

**Detailed Description:** This is an interventional open-label, single arm, multi-center study in pediatric subjects, age 6 through 18 years, who are diagnosed with autoimmune pulmonary alveolar proteinosis (aPAP).

The diagnosis of aPAP should be confirmed by an anti-GM-CSF antibody test and a history compatible with PAP based on patient symptoms, high resolution computed tomography of the lung, lung biopsy or bronchoalveolar lavage cytology.

The study consists of a 4-week screening period followed by a 48-week open-label treatment period. After completing the 48-week treatment or early withdrawal, subjects will enter a 4-week safety follow up period. The maximum treatment duration is 48-weeks, and the maximum study period will be 56 weeks. During the trial, lung lavage will be allowed as a rescue treatment in case of worsening of aPAP.

### Conditions Module

**Conditions:**

- Autoimmune Pulmonary Alveolar Proteinosis

**Keywords:**

- alveolar proteinosis

- autoimmune

- lung lavage

- GM-CSF

- children

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** Open-label study

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 5

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Molgramostim 300 mcg administered once daily via nebulizer for 48 weeks.

**Intervention Names:**

- Drug: Molgramostim

**Label:** molgramostim

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- molgramostim

**Description:** Molgramostim nebulizer solution will be administered once daily using a proprietary nebulizer optimized for the delivery of high molecular weight biologic compounds.

**Name:** Molgramostim

**Other Names:**

- Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF).

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** Adverse events (AEs), including clinically significant findings on pulmonary function tests and safety laboratory assessments and adverse events of special interest (AESIs; hypersensitivity and chest pain).

**Measure:** Adverse Events

**Time Frame:** 48 weeks

**Description:** Titers of anti-GM-CSF antibodies

**Measure:** Anti-GM-CSF Ab titer

**Time Frame:** 0, 4, 12,24,48 and 52 weeks

**Description:** Change from Baseline in forced expiratory volume in one second (FEV1) (% predicted)

**Measure:** FEV1

**Time Frame:** 24 and 48-weeks

**Description:** Change from Baseline in Forced vital capacity (FVC) (% predicted)

**Measure:** FVC

**Time Frame:** 24 and 48-weeks

#### Primary Outcomes

**Description:** Change in Hb-adjusted % predicted DLCO from Baseline.

**Measure:** DLCO

**Time Frame:** 24 weeks

#### Secondary Outcomes

**Description:** Change in Hb-adjusted % predicted DLCO from Baseline .

**Measure:** DLCO

**Time Frame:** 48-weeks

**Description:** Absolute change from Baseline in 6-minute walk distance (6MWD)

**Measure:** 6-minute walk distance

**Time Frame:** 24-weeks

**Description:** Absolute change from Baseline in 6-minute walk distance (6MWD).

**Measure:** 6-minute walk distance

**Time Frame:** 48-weeks

**Description:** Change from Baseline in Pediatric Quality of Life (PedsQLTM) Generic Core Scale score.

**Measure:** PedsQL

**Time Frame:** 24-weeks

**Description:** Change from Baseline in Pediatric Quality of Life (PedsQLTM) Generic Core Scale score.

**Measure:** PedsQL

**Time Frame:** 48-weeks

**Description:** Absolute change from Baseline in oxygen saturation (SpO2)

**Measure:** Oxygen Saturation (SpO2)

**Time Frame:** 24 weeks

**Description:** Absolute change from Baseline in oxygen saturation (SpO2)

**Measure:** Oxygen Saturation (SpO2)

**Time Frame:** 48 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Be ≥6 and \<18 years of age, at the time of signing the informed consent and informed assent (if applicable).
* Have a history of pulmonary alveolar proteinosis, based on examination of a lung biopsy, bronchoalveolar lavage cytology, or a high-resolution computed tomogram of the chest.
* Have a positive serum anti-GM-CSF autoantibody test result confirming aPAP.
* Have a hemoglobin (Hb)-adjusted diffusing capacity of the lung for carbon monoxide (DLCO) ≤70% predicted at Screening.

Exclusion Criteria:

* Have a diagnosis of hereditary (congenital) or secondary PAP, or a metabolic disorder of surfactant production.
* Have undergone treatment with Lung Lavage (WLL) within 1 month of Baseline

**Maximum Age:** 18 Years

**Minimum Age:** 6 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** yasmine.wasfi@savarapharma.com

**Name:** Yasmine Wasfi, MD, PhD,

**Phone:** 1 512 851 1364

**Role:** CONTACT

**Contact 2:**

**Email:** ray.pratt@savarapharma.com

**Name:** Raymond D Pratt, MD

**Phone:** 1 240 899 7058

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Cincinnati

**Country:** United States

**Facility:** Cincinnati Children's Hospital Medical Center

**State:** Ohio

**Zip:** 45229-3039

#### Overall Officials

**Official 1:**

**Affiliation:** Savara Inc.

**Name:** Yasmine Wasfi, MD, Ph.D.

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M27137

- Name: Respiratory Aspiration

- Relevance: LOW

- As Found: Unknown

- ID: M14503

- Name: Pulmonary Alveolar Proteinosis

- Relevance: HIGH

- As Found: Pulmonary Alveolar Proteinosis

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: HIGH

- As Found: Autoimmune Pulmonary Alveolar Proteinosis

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T568

- Name: Autoimmune Pulmonary Alveolar Proteinosis

- Relevance: HIGH

- As Found: Autoimmune Pulmonary Alveolar Proteinosis

### Condition Browse Module - Meshes

- ID: D000011649

- Term: Pulmonary Alveolar Proteinosis

- ID: D000001327

- Term: Autoimmune Diseases

### Intervention Browse Module - Ancestors

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

### Intervention Browse Module - Browse Leaves

- ID: M257633

- Name: Molgramostim

- Relevance: HIGH

- As Found: Desmoid

- ID: M219218

- Name: Sargramostim

- Relevance: HIGH

- As Found: Dihydroxyphenylalanine

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000082430

- Term: Molgramostim

- ID: C000081222

- Term: Sargramostim

### Misc Info Module

- Version Holder: 2024-05-31
