Proof of Concept Study Comparing FX006 to Kenalog®-40 in Patients With Post-Traumatic Osteoarthritis of the Knee

• Sponsor: Flexion Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02468583
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Duration (Months): 17
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study was a double-blind, randomized, parallel group, proof of concept study comparing FX006 to Kenalog®-40 (triamcinolone acetonide injectable suspension, USP) in patients with post-traumatic osteoarthritis of the knee.

Condition or Disease	Intervention/Treatment	Phase
Post-traumatic Osteoarthritis of the Knee	Drug: FX006 32 mg; Drug: TCA IR 40 mg	Phase 2

Detailed Description

This study was a double-blind, randomized, parallel group, proof of concept study patients with post-traumatic osteoarthritis (PTOA) of the knee. Approximately 124 eligible patients were intended to be randomized to one of the two treatment groups (1:1) and treated with a single intra-articular (IA) injection of:

• 32 mg of FX006

• 40 mg of Kenalog®-40 (triamcinolone acetonide injectable suspension, USP)

Each prospective patient underwent a screening evaluation to confirm a diagnosis of PTOA of the knee and concurrence with all other eligibility criteria. Patients were be treated on Day 1 (Baseline) and returned to the clinic at Weeks 4, 8 and 12 for evaluation of safety and efficacy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Parallel Group, Proof of Concept Study Comparing FX006 to Kenalog®-40 in Patients With Post-Traumatic Osteoarthritis of the Knee
• Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: FX006 32mg Single 5 mL intra-articular (IA) injection Extended-release formulation	Drug: FX006 32 mg; Experimental; Other Names: Zilretta
Active Comparator: TCA IR 40 mg Single 1 mL intra-articular (IA) injection Immediate-release formulation	Drug: TCA IR 40 mg; Comparator; Other Names: Kenalog®-40 Triamcinolone Acetonide Crystalline Suspension (TAcs)

Outcome Measures

Primary Outcome Measures

1. Average Change From Baseline in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores Over Weeks 5 to 10 [5-10 Weeks]

   The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."

Secondary Outcome Measures

1. Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores, Change From Baseline to Each Week and Average Change From Baseline Over Weeks 1 to 12 and Weeks 4 to 12 [12 Weeks]

   The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."

2. Proportion of Patients Experiencing a >20% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Each Week [12 Weeks]

3. Proportion of Patients Experiencing a >50% or >30% Decrease in Pain From Baseline in Weekly Mean of Average Daily 24-hr Pain Intensity Scores at Each Week [12 Weeks]

4. Proportion of Patients Experiencing Each of >50% or >30% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Each Week [12 Weeks]

5. WOMAC A (Pain Subscale) [12 weeks]

   change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12

6. WOMAC A1 (Pain on Walking Question) [12 weeks]

   change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12

7. WOMAC B (Stiffness) [12 weeks]

   change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12

8. WOMAC C (Function) [12 weeks]

   change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12

9. WOMAC (Total): [12 weeks]

   change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12

10. Knee Injury and Osteoarthritis Score (KOOS) [12 weeks]

    change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12

11. Patient Global Impression of Change (PGIC) at Weeks 4, 8 and 12 [12 weeks]

12. Clinical Global Impression of Change (CGIC) at Weeks 4, 8 and 12 [12 weeks]

13. Percent of Responders (Defined as Patients With High Improvement in Pain or Function) According to OMERACT-OARSI Criteria at Weeks 4, 8 and 12 [12 weeks]

14. Time to Onset of Pain Relief [Baseline to >30% improvement]

    Time to onset of pain relief in days is defined as the time from first dose to the first daily pain assessment showing >30% improvement from the weekly mean of the average daily (24-hr) pain intensity scores at Baseline

15. Average Weekly and Total Consumption of Rescue Medication [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions

• Male or female ≥20 and ≤50 years of age

• Diagnosis of post-traumatic OA of the knee

• Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee within 6 months prior to or at Screening

• Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale)

• Body mass index (BMI) ≤ 40 kg/m2

• Willingness to abstain from use of restricted medications and therapies during the study

Exclusion Criteria:

• Prior osteotomy of the index knee

• Any condition that could possibly confound the patient's assessment of index knee pain in the judgement of the Investigator (i.e., ipsilateral hip OA, gout, radicular low back pain and hip pain that is referred to the knee that could cause misclassifcation, pain in any other area of the lower extremeties or back that is equal to or greater than the index knee pain)

• Fibromyalgia, Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease

• History of, or clinical signs and symptoms of active infection of the index knee

• Crystal disease of the index knee within one month of Screening

• Disease secondary to surgical treatment of Shatzker grade IV, V, or VI tibial plateau fractures (OTA classification C2 or C3); surgical treatment of OTA calssifcation C2 or C3 distal femur fractures; or >2mm of articular incongruity after surgery

• IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening

• IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening

• Intramuscular (IM) or oral corticosteroids (investigational or marketed) within 1 month of Screening

• Any other IA investigational drug/biologic within 6 months of Screening

• Prior use of FX006

• Prior arthroplasty of any type of the index knee or planned/anticipated surgery of the index knee during the study period

• Type 1 or Type 2 diabetes requiring insulin

• Women of child-bearing potential not using effective contraception or who are pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Antonio Military Medical Center	San Antonio	Texas	United States	78234

Sponsors and Collaborators

• Flexion Therapeutics, Inc.

Investigators

• Study Director: Neil Bodick, MD, Flexion Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Flexion Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02468583
• Other Study ID Numbers: FX006-2014-007
• First Posted: Jun 11, 2015
• Last Update Posted: Aug 29, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by Flexion Therapeutics, Inc.: Osteoarthritis; Post-traumatic; Knee; Pain; Corticosteroid; Intra-articular; Injection
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; FX006; Triamcinolone diacetate

Study Results

Participant Flow

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	3 subjects received FX006 32 mg as a single 5 mL IA injection	3 subjects received TCA IR 40 mg as a single 1 mL IA injection
Period Title: Overall Study
STARTED	3	3
COMPLETED	3	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	FX006 32 mg	TCA IR 40 mg	Total
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection	Total of all reporting groups
Overall Participants	3	3	6
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	43	40	42
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	3 100%	3 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Average Change From Baseline in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores Over Weeks 5 to 10
Description	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."
Time Frame	5-10 Weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

2. Secondary Outcome

Title	Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores, Change From Baseline to Each Week and Average Change From Baseline Over Weeks 1 to 12 and Weeks 4 to 12
Description	The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates "no pain" and 10 indicates "pain as bad as you can imagine."
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

3. Secondary Outcome

Title	Proportion of Patients Experiencing a >20% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Each Week
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

4. Secondary Outcome

Title	Proportion of Patients Experiencing a >50% or >30% Decrease in Pain From Baseline in Weekly Mean of Average Daily 24-hr Pain Intensity Scores at Each Week
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

5. Secondary Outcome

Title	Proportion of Patients Experiencing Each of >50% or >30% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Each Week
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

6. Secondary Outcome

Title	WOMAC A (Pain Subscale)
Description	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

7. Secondary Outcome

Title	WOMAC A1 (Pain on Walking Question)
Description	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

8. Secondary Outcome

Title	WOMAC B (Stiffness)
Description	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

9. Secondary Outcome

Title	WOMAC C (Function)
Description	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

10. Secondary Outcome

Title	WOMAC (Total):
Description	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

11. Secondary Outcome

Title	Knee Injury and Osteoarthritis Score (KOOS)
Description	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

12. Secondary Outcome

Title	Patient Global Impression of Change (PGIC) at Weeks 4, 8 and 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

13. Secondary Outcome

Title	Clinical Global Impression of Change (CGIC) at Weeks 4, 8 and 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

14. Secondary Outcome

Title	Percent of Responders (Defined as Patients With High Improvement in Pain or Function) According to OMERACT-OARSI Criteria at Weeks 4, 8 and 12
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

15. Secondary Outcome

Title	Time to Onset of Pain Relief
Description	Time to onset of pain relief in days is defined as the time from first dose to the first daily pain assessment showing >30% improvement from the weekly mean of the average daily (24-hr) pain intensity scores at Baseline
Time Frame	Baseline to >30% improvement

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

16. Secondary Outcome

Title	Average Weekly and Total Consumption of Rescue Medication
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Given that the study was closed early, with only 5% of the planned study population enrolled, efficacy data were not analyzed.

Arm/Group Title	FX006 32 mg	TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection	TCA IR: Single 1 mL IA injection
Measure Participants	0	0

Adverse Events

Time Frame	Adverse Events were collected following IA administration through the final study visit at week 12.
Arm/Group Title	FX006 32 mg		TCA IR 40 mg
Arm/Group Description	FX006: Single 5 mL IA injection		TCA IR: Single 3 mL IA injection
All Cause Mortality
	FX006 32 mg		TCA IR 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Serious Adverse Events
	FX006 32 mg		TCA IR 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	FX006 32 mg		TCA IR 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/3 (66.7%)
Gastrointestinal disorders
Haemorrhoids	0/3 (0%)	0	1/3 (33.3%)	1
Infections and infestations
Tooth Infection	1/3 (33.3%)	1	0/3 (0%)	0
Bronchitis	0/3 (0%)	0	1/3 (33.3%)	1
Blood triglycerides increased	0/3 (0%)	0	1/3 (33.3%)	1
Injury, poisoning and procedural complications
Contusion	1/3 (33.3%)	1	0/3 (0%)	0
Investigations
Blood cholesterol increased	0/3 (0%)	0	1/3 (33.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/3 (33.3%)	1	1/3 (33.3%)	1
Nervous system disorders
Headache	2/3 (66.7%)	2	0/3 (0%)	0

Limitations/Caveats

This study was terminated early with only 5% of the planned study population enrolled, efficacy data were not analyzed.

More Information

Certain Agreements

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

There IS 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.