A Phase 1b Study of PUR1800 in Patients With COPD

NCT04759807 | Completed Phase 1

• 1 other identifier: 601-0016
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomised, placebo-controlled, double-blind 3-way crossover study in which PUR1800, or placebo is dosed daily for 14 consecutive days in adult subjects with stable COPD over three discrete TPs. Subjects will be randomised to one of the following 3 treatment sequences: Sequence Period 1 Period 2 Period 3

1. 1.Placebo PUR1800 250 μg PUR1800 500 μg
2. 2.PUR1800 250 μg Placebo PUR1800 500 μg
3. 3.PUR1800 250 μg PUR1800 500 μg Placebo

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Outcome Measures

Primary Outcomes (12)

• Incidence of treatment-emergent adverse events adult patients with stable COPD.

  Review of adverse events

  Day 1 through Day 28

• Incidence of intraday FEV1 declines (from pre-dose to post-dose) of ≥10%, ≥15%, and ≥20% adult patients with stable COPD.

  Review of spirometry data

  Day 1 through Day 28

• Respiratory rate

  Breaths per minute

  Day 1 through Day 28

• Blood presuure

  Systolic pressure over diastolic pressure

  Day 1 through Day 28

• Heart rate

  Beats per minute

  Day 1 through Day 28

• Oxygen saturation

  As a percentage

  Day 1 through Day 28

• Medical history findings

  Medical record review

  Day 1 through Day 28

• Physical examination findings

  Physician's notes

  Day 1 through Day 28

• Clinical laboratory parameters

  Lab reports with any out of range results flagged

  Day 1 through Day 28

• 12-Lead ECG findings

  ECG report and tracing

  Day 1 through Day 28

• Occurrence of PEFR decline of ≥ 30% from the established baseline PEFR

  Review of spirometry data

  Day 1 through Day 28

• Occurrence of administration of more than 12 inhalations of salbutamol per day over two consecutive days

  Review of concomitant medications administered

  Day 1 through Day 28

Secondary Outcomes (8)

• AUC0-t

  Day 1 through Day 14

• AUCinf inhaled PUR1800 in adult patients with stable COPD.

  Day 1 through Day 14

• CL

  Day 1 through Day 14

• Vss

  Day 1 through Day 14

• t1/2

  Day 1 through Day 14

Other Outcomes (1)

• Sputum RV1162 concentration

  at trough on Days 2, 7, 14, and at the baseline visits prior to TP2 and TP3 as well as the EOS visit after TP3.

Study Arms (3)

Placebo

PLACEBO COMPARATOR

The placebo designed for administration in the proposed clinical study consists of a dry powder composed of the same excipients as the active (sodium sulfate, mannitol and polysorbate 80), pre-metered into HPMC capsules at the same 5 mg powder fill weight as the active formulations. Subjects will receive 14 doses administered once daily in the morning.

Drug: Placebo Comparator

PUR1800 250 μg

ACTIVE COMPARATOR

The PUR1800 drug product intended for use in the proposed clinical study comprises bulk powder containing 5 wt% or 10 wt% RV1162 pre-metered into HPMC capsules for oral delivery via a passive DPI. The capsules contain 5 milligrams (mg) of the powder formulation, corresponding to 250 μg and 500 μg nominal dose strengths of RV1162. Subjects will receive 14 doses administered once daily in the morning.

Drug: PUR1800 250 ug

PUR1800 500 μg

ACTIVE COMPARATOR

The PUR1800 drug product intended for use in the proposed clinical study comprises bulk powder containing 5 wt% or 10 wt% RV1162 pre-metered into HPMC capsules for oral delivery via a passive DPI. The capsules contain 5 milligrams (mg) of the powder formulation, corresponding to 250 μg and 500 μg nominal dose strengths of RV1162. Subjects will receive 14 doses administered once daily in the morning.

Drug: PUR1800 500 ug

Interventions

Placebo Comparator DRUG

The placebo designed for administration in the proposed clinical study consists of a dry powder composed of the same excipients as the active (sodium sulfate, mannitol and polysorbate 80), pre-metered into HPMC capsules at the same 5 mg powder fill weight as the active formulations. Subjects will receive 14 doses administered once daily in the morning.

Placebo

PUR1800 250 ug DRUG

The PUR1800 drug product intended for use in the proposed clinical study comprises bulk powder containing 5 wt% or 10 wt% RV1162 pre-metered into HPMC capsules for oral delivery via a passive DPI. The capsules contain 5 milligrams (mg) of the powder formulation, corresponding to a 250 μg nominal dose strength of RV1162. Subjects will receive 14 doses administered once daily in the morning.

PUR1800 250 μg

PUR1800 500 ug DRUG

The PUR1800 drug product intended for use in the proposed clinical study comprises bulk powder containing 5 wt% or 10 wt% RV1162 pre-metered into HPMC capsules for oral delivery via a passive DPI. The capsules contain 5 milligrams (mg) of the powder formulation, corresponding to a 500 μg nominal dose strength of RV1162. Subjects will receive 14 doses administered once daily in the morning.

PUR1800 500 μg

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all the following:
• Male or female patients aged 40 to 75 years of age with a body mass index
• ≥ 17 and ≤ 35 kg/m2.
• Female patients must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method (See Section 9.4.1).
• Male patients with female partners of childbearing potential must be vasectomised with documented medical assessment of the surgical success or use highly effective contraception together with their female partner(s) (See Section 9.4.1).
• Female patients must agree not to donate ova/oocytes during the study and for 30 days after the last dose of IMP.
• Male patients must agree not to donate semen during the study and for 90 days after the last dose of IMP.
• Confirmed diagnosis by a physician of COPD with symptoms compatible with COPD for at least 1 year prior to screening.
• Severity of Disease: patients who conform to the current severity classification for GOLD Grade II/III disease in terms of post-bronchodilator spirometry at screening: Post-salbutamol FEV1/FVC ratio of \< 0.70. Post-salbutamol FEV1 ≥ 40 % and ≤ 80 % of predicted normal values (based on the Global Lung Function Initiative \[GLI-2012\]\[1\]).
• Current or previous tobacco smoker with a smoking history of ≥ 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent).
• Vital signs recorded from automated blood pressure equipment within the following normal ranges: Blood pressure; systolic value of 90 mmHg to 160 mmHg, diastolic value of 60 mmHg to 90 mmHg and pulse rate ≥ 60 and
• ≤100 beats per minute at screening and prior to randomisation.
• Able to provide written Informed Consent Form (ICF) prior to participation in any study-related activities, and to comply with the requirements of the study.
• Able to perform technically acceptable spirometry at screening.
• Able to produce a sputum sample of adequate quality at either the Screening or Baseline visit prior to randomisation.

You may not qualify if:

• Patients who meet any of the following are not eligible:
• Upper or lower respiratory tract infection within 6 weeks prior to screening or prior to randomisation.
• COPD exacerbation requiring oral steroids and/or antibiotics, within the 6 weeks prior to screening or prior to randomisation.
• Clinically significant abnormal laboratory values at screening that, in the opinion of the investigator would make the patient inappropriate for the study or put the patient at undue risk, specifically liver function tests (LFTs: aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], gamma-glutamyl transferase \[GGT\], total bilirubin) \>3 x upper limit of normal (ULN); hemoglobin \<10 gm/dL; absolute neutrophil count (ANC) \<1000; white blood cells (WBC) \>20,000; Platelets \<100,000 and \>500,000; prothrombin time (PT) \>14 seconds.
• QTcF of \>450 msec in males or \>470 msec in females on any of the three individual ECG measurements at screening or prior to randomisation.
• History of drug or alcohol abuse within the past 2 years prior to screening or prior to randomisation.
• History of regular alcohol consumption within 6 months prior to screening or prior to randomisation defined as an average weekly intake of \>21 units for males, or \>14 units for females, where one unit is equivalent to 8 g of alcohol: a half-pint (\~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Positive alcohol breath test result at screening or prior to randomisation.
• Positive urine drugs of abuse test result (unless in the opinion of the investigator this can be explained by the patient's current medications) at screening or prior to randomisation; unexpected or unexplained positive results may require discussion with Sponsor.
• Current users of e-cigarettes and those who have used these products within one month prior to screening or between screening and randomisation.
• Known sensitivity to the study drug or any of the excipients of the formulation, or history of clinically significant sensitivity to any agent that, in the opinion of the investigator, would make participation in the study inadvisable.
• Donated blood or blood products or had substantial loss of blood (more than 500 mL) within 3 months before the first administration of study drug, or intention to donate blood or blood products during the study.
• Participated in an interventional study involving an experimental therapeutic agent within 3 months of screening or prior to randomisation.
• Women who have a positive serum β-human chorionic gonadotropin (hCG) pregnancy test at screening or a positive urinary hCG pregnancy test prior to randomisation, is pregnant, lactating, or planning to become pregnant during the study.
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or HIV results. Patients who are HBs antibody positive or HB core antibody positive are not excluded provided the HBsAg result is negative. Patients who are HCV Ab positive are not excluded if a subsequent HCV RNA test is negative.

Sponsors & Collaborators

• Pulmatrix Inc.: lead

Study Sites (1)

Medicines Evaluation Unit Ltd.

Manchester, Wythenshawe, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Dave Singh, Prof

  The Medicines Evaluation Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: A computerised randomisation scheme will be created and shall be considered blinded. The randomisation is available only to the clinical research unit pharmacy staff that are preparing the drug who will not be involved in any other aspect of the study including administration of the drug. It will not be made available to the subjects, site(s) PI(s), or members of the staff responsible for the monitoring and evaluation of safety assessments. PUR1800 and placebo capsules will be of the same shape, size, and color to ensure that the blind is maintained. A subject's treatment assignment will only be unblinded when knowledge of the treatment is essential for the further clinical management of the subject on this study or may potentially impact the safety of subjects currently enrolled or subjects in subsequent enrollment.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: PUR1800, or placebo is dosed daily for 14 consecutive days in adult subjects with stable COPD over three discrete TPs. Subjects will be randomised to one of the following 3 treatment sequences: Sequence Period 1 Period 2 Period 3 1. Placebo PUR1800 250 μg PUR1800 500 μg 2. PUR1800 250 μg Placebo PUR1800 500 μg 3. PUR1800 250 μg PUR1800 500 μg Placebo

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 18, 2021
• Study Start: January 4, 2021
• Primary Completion: December 2, 2021
• Study Completion: December 2, 2021
• Last Updated: June 27, 2022

Record last verified: 2022-06

Locations

GB (1)