Inhaled Molgramostim (rhGM-CSF) in Healthy Adult Subjects

NCT02468908 | Completed Phase 1 DMC

• 1 other identifier: MOL-001
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, single ascending (SAD), and multiple ascending dose (MAD) study conducted at a single clinical site within the UK. Healthy male and female subjects (on non-child bearing potential) will be enrolled to investigate single inhaled doses of molgramostim at 3 dose levels (Part 1) and multiple inhaled doses at 2 dose levels (Part 2). The 2 doses in the multiple ascending dose regimens will be administered once daily (QD) for 6 consecutive days. The clinical indication for inhaled molgramostim is the treatment of respiratory diseases such as aPAP, bronchiectasis and cystic fibrosis. The Clinical trial will involve 42 healthy participants. The trial is expected to last approximately 4 months.

Conditions

Pulmonary Alveolar Proteinosis; Bronchiectasis; Cystic Fibrosis; Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (1)

• Number and severity of treatment-emergent Adverse Events (AEs) following single and multiple inhaled doses of molgramostim

  1-6 days

Secondary Outcomes (2)

• PK parameters: Area under the plasma concentration time curve (AUC), Peak Peak Plasma concentration - Cmax, Time to reach maximum observed serum concentration - tmax

  1-6 days

• PK parameters: Apparent terminal elimination rate constant - k(el) and Apparent terminal elimination rate constant - t(1/2)

  1-6 days

Other Outcomes (4)

• Development of antibodies to rhGM-CSF

  28 days

• Change from baseline in Whole Blood Celle Count (WBCC)

  7 days

• Change from baseline in exhaled fraction of Nitric Oxide (FeNO) measurements

  7 days

Study Arms (2)

Molgramostim nebuliser solution, inhaled

EXPERIMENTAL

Single dose 150, 300 and 600 ug, multiple dose 300 and 600 ug for 6 days

Drug: Molgramostim

Nebuliser solution, inhaled

PLACEBO COMPARATOR

Inhaled nebuliser solution

Drug: Placebo

Interventions

Molgramostim DRUG

Also known as: Granulocyte Macrophage-Colony Stimulating Factor (rhGM-CSF)

Molgramostim nebuliser solution, inhaled

Placebo DRUG

Also known as: Nebuliser solution

Nebuliser solution, inhaled

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult, male or female, 18- 55 years of age, inclusive, at screening.
• Life-long non smoker who has not used nicotine containing products.
• Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, spirometry, vital signs, or ECGs, as deemed by the PI.
• Females must be of non-child bearing potential who must have undergone one of the following sterilization procedures at least 6 months prior to dosing in Part 1 or prior to the first dose in Part 2:
• hysteroscopic sterilization;
• bilateral tubal ligation or bilateral salpingectomy;
• hysterectomy;
• bilateral oophorectomy; or be postmenopausal with amenorrhea for at least 1 year prior to dosing in Part 1 or prior to the first dose in Part 2, and FSH serum levels consistent with postmenopausal status as per PI's judgment.
• A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to study start. A male who has been vasectomized less than 4 months prior to study start must follow the same restrictions as a non vasectomized male).
• If male must agree not to donate sperm from dosing in Part 1 or from the first dose in Part 2, until 90 days following last dose.
• Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

You may not qualify if:

• Subject is mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical condition(s) (including ongoing active infections) or psychiatric condition(s) or disease(s) in the opinion of the PI.
• History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• Abnormal spirometry test results, in the opinion of the PI.
• History of severe or unexplained adverse reactions during aerosol delivery of any medicinal product.
• History or presence of alcoholism or drug abuse within the past 2 years prior to screening.
• History or presence of hypersensitivity or idiosyncratic reaction to molgramostim or to related compounds (i.e., Growgen®, Leucomax®, Leukine®, Topleucon™).
• Clinically significant history or presence of ECG abnormalities such as second- or third degree atrioventricular block, evidence, or family history of prolonged QT syndrome.
• Allergy to bandaids, adhesive dressing, or medical tape.
• Positive urine drug at screening or check in.
• Positive alcohol test at check-in.
• Drink alcohol in excess of 21 units per week for males or 14 units per week for females, with one unit = 150 mL of wine or 360 mL of beer or 45 mL of 45% alcohol.
• Positive urine cotinine at screening and check-in.
• Positive results at screening for HIV, HBsAg, or HCV.
• Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at screening.

Sponsors & Collaborators

• Savara Inc.: lead
• Celerion: collaborator

Study Sites (1)

Celerion

Belfast, BT9 6AD, United Kingdom

Location

Related Publications (1)

• Trapnell BC, Carey BC, Robinson BR. Pharmacokinetics and pharmacodynamics of inhaled molgramostim in healthy people. BMJ Open Respir Res. 2025 Sep 18;12(1):e002832. doi: 10.1136/bmjresp-2024-002832.

  PMID: 40973220 DERIVED

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis; Bronchiectasis; Cystic Fibrosis; Respiratory Distress Syndrome

Interventions

molgramostim; Colony-Stimulating Factors; regramostim

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Bronchial Diseases; Pancreatic Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Johnston Steward, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2015
• First Posted: June 11, 2015
• Study Start: May 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: February 23, 2017

Record last verified: 2015-11

Locations

GB (1)