Inhaled Molgramostim (rhGM-CSF) in Healthy Adult Subjects

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Brief Title

Inhaled Molgramostim (rhGM-CSF) in Healthy Adult Subjects

Official Title

A Randomized, Double-Blind, Placebo-Controlled, Single-Centre, Single Ascending Dose and Multiple Ascending Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Molgramostim When Administered by Inhalation to Healthy Adult Subjects

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.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

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

Condition

Pulmonary Alveolar Proteinosis

Intervention

Molgramostim

Study Arms / Comparison Groups

 Molgramostim nebuliser solution, inhaled
Description:  Single dose 150, 300 and 600 ug, multiple dose 300 and 600 ug for 6 days

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

42

Start Date

May 2015

Completion Date

October 2015

Primary Completion Date

October 2015

Eligibility Criteria

        Inclusion Criteria:

          1. Healthy, adult, male or female, 18- 55 years of age, inclusive, at screening.

          2. Life-long non smoker who has not used nicotine containing products.

          3. Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening.

          4. Medically healthy with no clinically significant medical history, physical
             examination, laboratory profiles, spirometry, vital signs, or ECGs, as deemed by the
             PI.

          5. 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.

          6. 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).

          7. 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.

          8. Understands the study procedures in the informed consent form (ICF), and be willing
             and able to comply with the protocol.

        Exclusion Criteria:

          1. 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.

          2. 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.

          3. 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.

          4. Abnormal spirometry test results, in the opinion of the PI.

          5. History of severe or unexplained adverse reactions during aerosol delivery of any
             medicinal product.

          6. History or presence of alcoholism or drug abuse within the past 2 years prior to
             screening.

          7. History or presence of hypersensitivity or idiosyncratic reaction to molgramostim or
             to related compounds (i.e., Growgen®, Leucomax®, Leukine®, Topleucon™).

          8. Clinically significant history or presence of ECG abnormalities such as second- or
             third degree atrioventricular block, evidence, or family history of prolonged QT
             syndrome.

          9. Allergy to bandaids, adhesive dressing, or medical tape.

         10. Positive urine drug at screening or check in.

         11. Positive alcohol test at check-in.

         12. 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.

         13. Positive urine cotinine at screening and check-in.

         14. Positive results at screening for HIV, HBsAg, or HCV.

         15. Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg at
             screening.

         16. Seated heart rate is lower than 45 bpm or higher than 99 bpm at screening.

         17. QTcF interval is >430 msec (males) or >450 msec (females) at screening or deemed
             clinically abnormal by the PI.

         18. Unable to refrain from or anticipates the use of:

               -  Any drug, including prescription and non prescription medications, herbal
                  remedies, or vitamin supplements beginning 14 days prior to dosing in Part 1 or
                  prior to the first dose in Part 2, and throughout the study. Hormone replacement
                  therapy (HRT) is not permitted in this study and within 3 months prior to
                  screening. During the study paracetamol (up to 2 g per 24 hours) may be
                  administered at the discretion of the PI.

               -  Any drugs known to be significant inducers of CYP enzymes and/or P gp, including
                  St. John's Wort, for 28 days prior to dosing in Part 1 or prior to the first dose
                  in Part 2, and throughout the study. Appropriate sources will be consulted by the
                  PI or designee to confirm lack of PK/PD interaction with study drug.

         19. Have been on a diet incompatible with the on study diet, in the opinion of the PI,
             within the 28 days prior to the first dose of study drug, and throughout the study.

         20. Haemoglobin or total WBC outside the normal range at screening.

         21. Donation of blood or plasma within 90 days prior to dosing in Part 1 or prior to the
             first dose in Part 2.

         22. Donation of bone marrow within the last 6 months prior to dosing in Part 1 or prior to
             the first dose in Part 2.

         23. Participation in another clinical trial within 90 days prior to dosing in Part 1 or
             prior to the first dose in Part 2.
      

Gender

All

Ages

18 Years - 55 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Johnston Steward, MD, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT02468908

Organization ID

MOL-001


Responsible Party

Sponsor

Study Sponsor

Savara Inc.

Collaborators

 Celerion

Study Sponsor

Johnston Steward, MD, Principal Investigator, Celerion


Verification Date

November 2015