Healthy VolunteersPhase 1NCT01627002

A Phase 1, First in Human Study to Investigate the Safety and Tolerability of PA401

A Phase 1 study testing PA401 in people with Healthy Volunteers, run by ProtAffin Biotechnologie AG at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The purpose of this study is to examine the safety, tolerability, immunogenicity and the way the body absorbs, distributes, breaks down and excretes various increasing single and multiple subcutaneous doses of PA401 in healthy subjects. Read more about this study

Who is it for?: Ages 18 to 65 years, men onlyHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: PA401
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 49 participants
Where: 1 siteUnited Kingdom
Study dates: May 2012to Apr 2013
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
Men only
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Healthy adult males aged 18 to 65 years

Who cannot join

Subjects with a clinically relevant medical history

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Quintiles
London, SE1 1YR

Other trials in United Kingdom

About this study

Official title: A Phase 1, FIH, Double-blind, Randomised Placebo-controlled Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of PA401, and the Effects of PA401 Following LPS Challenge, in Healthy Subjects

This study will also look at the effect of PA401 on inflammation in the lungs following an inhaled lipopolysaccharide (LPS) challenge (LPS is a bacterial cell wall fragment) and sputum induction (a procedure performed to help to cough up sputum (phlegm)) after a single subcutaneous dose of two dose levels.

Conditions: Healthy Volunteers
Being tested: PA401, Placebo
Keywords: Phase 1, First in Human, Healthy Volunteers, Lipopolysaccharide Challenge

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PA401Biological
Part A of Study: Subcutaneous, 0.1mg to 50mg, single ascending doses Part B of Study: Subcutaneous, up to 17.1mg, single dose
PlaceboOther
Subcutaneous

Study groups in NCT01627002
Study group	Role	What they receive
PA401	Experimental	PA401 is a potent inhibitor of neutrophil activation and transmigration under development as a novel parenteral anti-inflammatory therapy for respiratory indications such as chronic obstructive pulmonary disease (COPD) and Cystic Fibrosis (CF). PA401 is a genetically engineered and recombinantly expressed mutant of the bioactive form of human interleukin-8. Receives: Biological: PA401
Placebo	Placebo comparator	Placebo Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Treatment Emergent Adverse Events
Measured: up to 14 days post dose
Immunogenicity
Anti-drug antibody data
Measured: Up to 28 days post dose
Assessment of the Effect of PA401 on Induced Sputum Total Neutrophils
Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils
Measured: 5.5 hours post dose

Secondary outcomes (5)

Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)
Measured: Up to 12 time-points up to 48 hours post dose
Pharmacokinetic Parameters: Time of Occurrence of the Maximum Observed Plasma Concentration (Tmax)
Measured: Up to 12 time-points up to 48 hours post dose
Pharmacokinetic Parameters: Terminal Half-life (t1/2)
Measured: Up to 12 time-points up to 48 hours post dose
Pharmacokinetic Parameters: Area Under the Plasma Concentration-time Curve From Zero to Infinity
Measured: Up to 12 time-points up to 48 hours post dose
Assessment of the Effect of PA401 on Induced Sputum Percentage Neutrophils
Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils
Measured: 5.5 hours post dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2012Apr 2013

First posted25 Jun 2012 (estimated)
Study startMay 2012
Primary completionApr 2013
Study completionApr 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 49 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01627002
Sponsor's protocol ID: PA401/01
Other IDs: 2012-001189-14
Status last verified: Jul 2013
First submitted: 12 Jun 2012
Last updated: 23 Sep 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Healthy Volunteers trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, FIH, Double-blind, Randomised Placebo-controlled Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of PA401, and the Effects of PA401 Following LPS Challenge, in Healthy Subjects
ClinicalTrials.gov ID: NCT01627002
Acronym / sponsor ID: PA401/01
Conditions: Healthy Volunteers
Keywords: Phase 1, First in Human, Healthy Volunteers, Lipopolysaccharide Challenge
Phase: Phase 1
Study type: Interventional
Recruitment status: Terminated
Enrolment: 49 participants (actual)
Lead sponsor: ProtAffin Biotechnologie AGIndustry (pharma, biotech, devices)
Study start: May 2012
Primary completion: Apr 2013 (actual)
Study completion: Apr 2013 (actual)
First posted: 25 Jun 2012 (estimated)
Results: Posted 23 Sep 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
PA401	Experimental	Biological: PA401PA401 is a potent inhibitor of neutrophil activation and transmigration under development as a novel parenteral anti-inflammatory therapy for respiratory indications such as chronic obstructive pulmonary disease (COPD) and Cystic Fibrosis (CF). PA401 is a genetically engineered and recombinantly expressed mutant of the bioactive form of human interleukin-8.
Placebo	Placebo comparator	Other: PlaceboPlacebo

Who may qualify

Ages: 18 to 65 years
Sex: Male only
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Healthy adult males aged 18 to 65 years

Key exclusion criteria (1 listed)

Subjects with a clinically relevant medical history

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PA401Part A of Study: Subcutaneous, 0.1mg to 50mg, single ascending doses Part B of Study: Subcutaneous, up to 17.1mg, single dose	Biological	PA401
PlaceboSubcutaneous	Other	Placebo

Primary outcome

Treatment Emergent Adverse Events
Time frame: up to 14 days post dose
Immunogenicity
Time frame: Up to 28 days post dose
Anti-drug antibody data
Assessment of the Effect of PA401 on Induced Sputum Total Neutrophils
Time frame: 5.5 hours post dose
Induced sputum was collected 6 hours after lipopolysaccharide challenge (5.5 hours following dosing) and assessed for neutrophils

5 secondary outcomes

Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)
Time frame: Up to 12 time-points up to 48 hours post dose
Pharmacokinetic Parameters: Time of Occurrence of the Maximum Observed Plasma Concentration (Tmax)
Time frame: Up to 12 time-points up to 48 hours post dose
Pharmacokinetic Parameters: Terminal Half-life (t1/2)
Time frame: Up to 12 time-points up to 48 hours post dose
Pharmacokinetic Parameters: Area Under the Plasma Concentration-time Curve From Zero to Infinity
Time frame: Up to 12 time-points up to 48 hours post dose
Assessment of the Effect of PA401 on Induced Sputum Percentage Neutrophils
Time frame: 5.5 hours post dose

Results and safety

Results posted to the registry on 23 Sep 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A PA401 0.1 mg	4	4
Part A PA401 0.3 mg	4	4
Part A PA401 1.0 mg	4	4
Part A PA401 3.0 mg	4	4
Part A PA401 10 mg	2	2
Part A Placebo	9	9
Part B PA401 1.0 mg	10	10
Part B PA401 3.0 mg	5	5
Part B Placebo	7	7

Primary outcome: Treatment Emergent Adverse Events

Time frame: up to 14 days post dose. Number. Unit: Participants

Measure	Part A PA401 0.1 mg n = 4	Part A PA401 0.3 mg n = 4	Part A PA401 1.0 mg n = 4	Part A PA401 3.0 mg n = 4	Part A PA401 10 mg n = 2	Part A Placebo n = 9	Part B PA401 1.0 mg n = 10	Part B PA401 3.0 mg n = 5	Part B Placebo n = 7
Value	3	3	4	2	2	3	7	5	4

Population analysed: Safety analyses were performed on all subjects who receive a dose of PA401 or placebo and who had any post-dose measurements

Primary outcome: Immunogenicity

Time frame: Up to 28 days post dose. Number. Unit: participants

Measure	Part A PA401 0.1 mg n = 4	Part A PA401 0.3 mg n = 4	Part A PA401 1.0 mg n = 4	Part A PA401 3.0 mg n = 4	Part A PA401 10 mg n = 2	Part A Placebo n = 9	Part B PA401 1.0 mg n = 10	Part B PA401 3.0 mg n = 5	Part B Placebo n = 7
Day 1 anti-drug antibody (ADA) positive	0	0	0	0	0	0	0	0	0
Day 1 ADA positive and cross-reactive with IL-8	0	0	0	0	0	0	0	0	0
Day 1 Pre-existing IL-8 autoantibodies	1	0	0	0	0	0	0	0	0
Day 15 ADA positive	0	0	0	0	0	0	0	0	0
Day 15 ADA positive and cross-reactive with IL-8	0	0	0	0	0	0	0	0	0
Day 15 Pre-existing IL-8 autoantibodies	1	0	0	0	0	0	0	0	0
Day 29 ADA positive	0	0	0	0	0	0	0	0	0
Day 29 ADA positive and cross-reactive with IL-8	0	0	0	0	0	0	0	0	0

Population analysed: Safety analyses were performed on all subjects who received a dose of PA401 or placebo and who had any post-dose assessments

Primary outcome: Assessment of the Effect of PA401 on Induced Sputum Total Neutrophils

Time frame: 5.5 hours post dose. Least squares mean (95% Confidence Interval). Unit: x10e6 cells/g

Measure	Part B 3.0 mg PA401 n = 5	Part B 1.0 mg PA401 n = 10	Part B Placebo n = 7
Value	11.6882 (2.8474 to 20.5290)	7.7274 (1.4038 to 14.0511)	12.7241 (5.1749 to 20.2733)

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 14 days post dose. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A PA401 0.1 mg	0 of 4 (0%)	3 of 4 (75%)	Not reported
Part A PA401 0.3 mg	0 of 4 (0%)	3 of 4 (75%)	Not reported
Part A PA401 1.0 mg	0 of 4 (0%)	4 of 4 (100%)	Not reported
Part A PA401 3.0 mg	0 of 4 (0%)	2 of 4 (50%)	Not reported
Part A PA401 10 mg	1 of 2 (50%)	2 of 2 (100%)	Not reported
Part A Placebo	0 of 9 (0%)	3 of 9 (33.3%)	Not reported
Part B PA401 1.0 mg	0 of 10 (0%)	7 of 10 (70%)	Not reported
Part B PA401 3.0 mg	0 of 5 (0%)	5 of 5 (100%)	Not reported
Part B Placebo	0 of 7 (0%)	4 of 7 (57.1%)	Not reported

Limitations and caveats (from the sponsor): Part B of the study was terminated early which led to a small number of subjects analyzed. Pharmacokinetic parameters were not calculated for Part A 0.3mg and 10 mg PA401

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jim Ritter, MD principal investigator

Quintiles, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PA401 in people with Healthy Volunteers, run by ProtAffin Biotechnologie AG at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Emergent Adverse Events (time frame: up to 14 days post dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01627002.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2013.