Assessment of the Safety, Tolerability and Efficacy of MEDI8968 in Subjects with Moderate to Severe Hidradenitis Suppurativa

Study identifier:D5440C00001

ClinicalTrials.gov identifier:NCT01838499

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase IIa Randomized, Double-Blind, Placebo-controlled, Multicenter Study to Assess the Safety, Tolerability and Preliminary Efficacy of MEDI8968 in Subjects with Moderate to Severe Hidradenitis Suppurativa

Medical condition

Hidradenitis Suppurativa

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

224

Study type

Interventional

Age

18 Years - 65 Years

Date

Study Start Date: 01 May 2013

Primary Completion Date: 01 Oct 2014

Study Completion Date: 01 Oct 2014

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2016 by AstraZeneca

Collaborators

ICON plc, Covance, PHT corporation

Inclusion and exclusion criteria

Location

Research Site

Atlanta, GA, United States

Location

Research Site

Forest Hills, NY, United States

Location

Research Site

Rapid City, SD, United States

Location

Research Site

San Diego, CA, United States

Location

Research Site

Philadelphia, PA, United States

Location

Research Site

Skokie, IL, United States

Location

Research Site

West Dundee, IL, United States

Location

Research Site

High Point, NC, United States

Arms	Assigned Interventions
Experimental: MEDI8968	Biological/Vaccine: MEDI8968 SC injection at baseline, Week 4 and Week 8 Other Name: Investigational Product
Placebo Comparator: Saline	Biological/Vaccine: Saline SC injection at baseline, Week 4 and Week 8 Other Name: Placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
221 subjects enrolled, 109 randomised. Enrolment for ERF based on info databased, as per programmed outputs and the CSR - the criteria being to have provided written consent. 3 additional patients were accounted for in the PRF. M and F subjects with moderate to severe HS were randomised to MEDI8968 or Placebo. 29 centres in the US involved.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomisation to treatment was stratified by PGA score on the day of randomisation (Stratum 1=PGA score of 3; Stratum 2=PGA score of 4 or 5).

Reporting Groups

	Description
MEDI8968	SC injection
Saline	SC injection

Participant Flow: Overall Study

	MEDI8968	Saline
STARTED	55	54
COMPLETED	31	37
NOT COMPLETED	24	17
Protocol Violation	0	1
Lost to Follow-up	2	4
Lack of Efficacy	1	2
Adverse Event	2	1
Withdrawal by Subject	19	9

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Full Analysis Set

Reporting Groups

	Description
MEDI8968	SC injection
Saline	SC injection

Baseline Measures

	MEDI8968	Saline	Total
Number of Participants [units: Participants]	55	54	109
Age Continuous [units: Years] Mean ± Standard Deviation	37.5 ± 11.08	36.4 ± 12.42	36.9 ± 11.72
Gender, Male/Female [units: Participants]
Female	45	38	83
Male	10	16	26

Outcome Measures

1. Primary Outcome Measure: 1) Percentage of subjects achieving a clinically relevant response in Physician Global Assessment (PGA), with score 0,1 or 2 from baseline to 12 weeks [ Time Frame: 12 weeks ]

Measure Type	Primary
Measure Name	1) Percentage of subjects achieving a clinically relevant response in Physician Global Assessment (PGA), with score 0,1 or 2 from baseline to 12 weeks
Measure Description	Percentage of subjects achieving a clinically significant response measured by the proportion of subjects who achieve 0, 1, or 2 PGA by the end of week 12
Time Frame	12 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS

Reporting Groups

	Description
MEDI8968	SC injection
Saline	SC injection

Measured Values

	MEDI8968	Saline
Number of Participants Analyzed [units:participants]	55	54
1) Percentage of subjects achieving a clinically relevant response in Physician Global Assessment (PGA), with score 0,1 or 2 from baseline to 12 weeks [units: % of patients]
Responders (%)	23.6	18.5
Non-responders (%)	76.4	81.5

Statistical Analysis 1 for 1) Percentage of subjects achieving a clinically relevant response in Physician Global Assessment (PGA), with score 0,1 or 2 from baseline to 12 weeks

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	>0.05
Other^[5]	0.051
80% Confidence Interval	( -0.067 to 0.169 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of proportion of Responders for Physician’s Global Assessment (PGA score 0, 1 or 2) at Week 12 - LOCF. Difference in proportions MEDI8968 - placebo. Wald asymptotic confidence limits calculated.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	MEDI8968 - placebo

2. Secondary Outcome Measure: 2) Subject’s global Impression of change reported on PGIC scale (1-7 point scale ranging from 1 "very much improved" to 7 "very much worse") [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	2) Subject’s global Impression of change reported on PGIC scale (1-7 point scale ranging from 1 "very much improved" to 7 "very much worse")
Measure Description	Percentage of subjects achieving a clinically significant response measured by the proportion of subjects who are "minimally improved", "much improved" or "very much improved" on the Patient's Global Impression of Change (PGIC)
Time Frame	12 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
MEDI8968	SC injection
Saline	SC injection

Measured Values

	MEDI8968	Saline
Number of Participants Analyzed [units:participants]	55	54
2) Subject’s global Impression of change reported on PGIC scale (1-7 point scale ranging from 1 "very much improved" to 7 "very much worse") [units: % of patients]
Responders (%)	49.1	55.6
Non-Responders (%)	50.9	44.4

Statistical Analysis 1 for 2) Subject’s global Impression of change reported on PGIC scale (1-7 point scale ranging from 1 "very much improved" to 7 "very much worse")

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	Mixed Models Analysis
P-Value^[4]	>0.05
Other^[5]	-0.065
80% Confidence Interval	( -0.205 to 0.076 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Difference in proportions MEDI8968 - placebo. Wald asymptotic confidence limits calculated.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Change from baseline to 12 weeks in Numerical Assessment Scale Numerical Rating Scale for pain [ Time Frame: 12 weeks ]

Measure Type	Secondary
Measure Name	Change from baseline to 12 weeks in Numerical Assessment Scale Numerical Rating Scale for pain
Measure Description	Assessment of change in pain via Numerical Rating Scale. Daily pain is reported by the subject using an 11-point 0 (no pain) to 10 (worst pain imaginable) numeric rating scale. Baseline score is the average of the values collected in the 7 days prior to first dose of study drug. Each Visit score is the average of the values collected in the 7 days prior to that visit.
Time Frame	12 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS (LOCF)

Reporting Groups

	Description
MEDI8968	SC injection
Saline	SC injection

Measured Values

	MEDI8968	Saline
Number of Participants Analyzed [units:participants]	50	50
Change from baseline to 12 weeks in Numerical Assessment Scale Numerical Rating Scale for pain [units: changes in scores on a scale] Least Squares Mean (Standard Error)
Week 4	-1.09 (0.35)	-1.02 (0.36)
Week 8	-1.76 (0.36)	-1.31 (0.36)
Week 12	-1.79 (0.46)	-1.76 (0.47)

Statistical Analysis 1 for Change from baseline to 12 weeks in Numerical Assessment Scale Numerical Rating Scale for pain

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.945
Other^[5]	-0.03
80% Confidence Interval	( -0.63 to 0.57 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Analysis of change from baseline (Week 12) estimated from ANCOVA model with tmt group and PGA stratum at randomisation included in the model and average daily pain at baseline as a covariate
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	MEDI8968 - Placebo

Serious Adverse Events

Time Frame	24 weeks. However, if a subject withdraws from treatment for any reason prior to week 24, the subject should continue to be seen up to 16 weeks after his/her last dose.
Additional Description	In the tables below all the SAEs are presented. In the Other Adverse events tables please note that a Frequency Threshold of 5% has been applies to reporting the AEs and associated summaries. If, within a treatment group the frequency >= 5%, the associated information has been presented for both treatment arms.

Reporting Groups

	Description
MEDI8968	SC injection
Saline	SC injection

Serious Adverse Events

MEDI8968

Saline

Total, serious adverse events

# participants affected / at risk

2/55 (3.64%)

2/54 (3.70%)

Infections and infestations

Bacteraemia¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Infections and infestations

Bacterial infection¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

1/55 (1.82%)

0/54 (0.00%)

# events

Infections and infestations

Staphylococcal infection¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Gastrointestinal disorders

Colitis¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Gastrointestinal disorders

Diverticulum¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Hepatobiliary disorders

Cholelithiasis¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Metabolism and nutrition disorders

Hypomagnesemia¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

0/55 (0.00%)

1/54 (1.85%)

# events

Infections and infestations

Pheumonia¹,^†

# participants affected / at risk

2/55 (3.64%)

0/54 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 17.0

Other Adverse Events

Time Frame	24 weeks. However, if a subject withdraws from treatment for any reason prior to week 24, the subject should continue to be seen up to 16 weeks after his/her last dose.
Additional Description	In the tables below all the SAEs are presented. In the Other Adverse events tables please note that a Frequency Threshold of 5% has been applies to reporting the AEs and associated summaries. If, within a treatment group the frequency >= 5%, the associated information has been presented for both treatment arms.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
MEDI8968	SC injection
Saline	SC injection

Other Adverse Events

MEDI8968

Saline

Total, other (not including serious) adverse events

# participants affected / at risk

8/55 (14.55%)

2/54 (3.70%)

Infections and infestations

Pheumonia¹,^†

# participants affected / at risk

3/55 (5.45%)

0/54 (0.00%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

3/55 (5.45%)

2/54 (3.70%)

# events

General disorders

Fatigue¹,^†

# participants affected / at risk

3/55 (5.45%)

0/54 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 17.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The trial terminated early due to lack of efficacy. An interim analysis was conducted after the first 61 subjects at 12 weeks and showed no evidence of MEDI8968 activity in reducing (HS) severity or pain over that seen with placebo.

Results Point of Contact

Name/Title:	Humphrey Gardner MD FCAP
Organization:	AstraZeneca
Phone	+1 781 839 4523
E-mail:	[email protected]

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

Richard Finkelman

Investigators

Principal Investigator

Robert AK Lee

University of California at San Diego

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Trial Results Summaries