AP-003-C Study to Confirm the Efficacy of Ampion™ in Adults With Pain Due to Severe Osteoarthritis of the Knee

• Sponsor: Ampio Pharmaceuticals. Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03182686
• Collaborator: (none)
• Enrollment: 168
• Locations: 13
• Arms: 2
• Actual Duration (Months): 5.6
• Patients Per Site: 12.9
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

This is a phase 3 randomized study to confirm the efficacy of an intra-articular injection of Ampion™ in adults with pain due to severe osteoarthritis of the knee.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee; Knee Osteoarthritis; Knee Arthritis; Knee Pain Chronic	Biological: 4 mL injection of Ampion; Drug: 4 mL Injection of Placebo	Phase 3

Detailed Description

A Randomized Study to Confirm the Efficacy of an Intra-Articular Injection of Ampion™ in Adults With Pain Due to Severe Osteoarthritis of the Knee

There will be a 7-day screening period for each subject followed by a 12-week participation period.

The primary trial objective is to evaluate the clinical efficacy of Ampion using the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) (using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) 3.1 Index and Patient's Global Assessment as assessments).

The secondary trial objectives are to evaluate the safety of a single intra-articular injection (4 mL) of Ampion.

Study Design

• Study Type: Interventional
• Actual Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized Study to Confirm the Efficacy of an Intra-Articular Injection of Ampion™ in Adults With Pain Due to Severe Osteoarthritis of the Knee
• Actual Study Start Date: Jun 19, 2017
• Actual Primary Completion Date: Dec 7, 2017
• Actual Study Completion Date: Dec 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMPION™ 4 mL dose 4 mL injection of Ampion	Biological: 4 mL injection of Ampion; 4 mL injection of Ampion
Placebo Comparator: Placebo 4 mL dose 4 mL injection of Placebo	Drug: 4 mL Injection of Placebo; 4 mL Injection of Placebo; Other Names: 0.9% Saline

Outcome Measures

Primary Outcome Measures

1. Number of Participants Classified as Responders [Determined from Baseline to 12 Weeks]

   Using the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of WOMAC A Pain subscore, WOMAC C Function subscore, and PGA as composite endpoints. A patient in this study will be considered a responder for the purpose of efficacy analysis if the following criteria are met: (1) demonstration of ≥ 50% improvement AND a 1.0-unit change in pain OR 1.0-unit change in function OR If the patient does not meet this criterion, then the patient must demonstrate at least 2 of the following: Improvement in pain (WOMAC A) ≥20% and a 0.5 point absolute change in pain from Baseline on the 5-point Likert scale Improvement in function (WOMAC C) ≥20% and a 0.5 point absolute change in function from Baseline on the 5-point Likert scale Improvement in patient global assessment (PGA) ≥20% and a 0.5 point absolute change in function from Baseline on the 5-point Likert scale

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Able to provide written informed consent to participate in the study;

• Willing and able to comply with all study requirements and instructions of the site study staff;

• Must be ambulatory;

• Study knee must have a clinical diagnosis of osteoarthritis (OA) supported by radiological evidence (Kellgren Lawrence Grade IV) which is assessed locally (x-rays within the past 6 months of screening are acceptable);

• Moderate to moderately-severe OA pain in the study knee (rating of at least 1.5 on the WOMAC A, 5-point Likert Pain Subscale);

• Moderate to moderately-severe OA function in the study knee (rating of at least 1.5 on the WOMAC C, 5-point Likert Function Subscale);

• WOMAC A, 5-point Likert pain subscale <1.5 in the contralateral knee;

• Ability to discontinue non-steroidal anti-inflammatory drug (NSAID) use at Screening visit and/or 72 hours prior to the Baseline visit and for the duration of the clinical study (low-dose aspirin (81 mg) is allowed during the study);

• No analgesia (including acetaminophen) taken 24 hours prior to an efficacy measure;

• No known clinically significant liver abnormality (e.g. cirrhosis, transplant, etc.).

Exclusion Criteria:

• As a result of medical review and screening investigation, the Principal Investigator considers the subject unfit for the study

• A history of allergic reactions to human albumin (reaction to non-human albumin such as egg albumin is not an exclusion criterion)

• A history of allergic reactions to excipients in 5% human albumin (N-acetyltryptophan, sodium caprylate)

• Presence of tense effusions

• Inflammatory or crystal arthropathies, acute fractures, history of aseptic necrosis or joint replacement in the affected knee, as assessed locally by the Principal Investigator

• Isolated patella femoral syndrome, also known as chondromalacia

• Any other disease or condition interfering with the free use and evaluation of the study knee for the duration of the trial (e.g. cancer, congenital defects, spine osteoarthritis)

• Major injury to the study knee within the 12 months prior to screening

• Severe hip osteoarthritis ipsilateral to the study knee

• Any pain that could interfere with the assessment of study knee pain (e.g. pain in any other part of the lower extremities, pain radiating to the knee)

• Any pharmacological or non-pharmacological treatment targeting OA started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study

• Pregnancy or planning to become pregnant during the study

• Use of the following medications:

1. No intra-articular (IA) injected medications in the study knee during the study (or 12 weeks prior to Baseline).

2. No analgesics containing opioids.

3. NSAIDs are not permitted during the study; acetaminophen is available as a rescue medication during the study from the provided supply.

4. No topical treatment on the study knee during the study

5. No significant anticoagulant therapy (e.g. Heparin or Lovenox) during the study (treatment such as low-dose Aspirin (81 mg) and Plavix are allowed)

6. No systemic treatments that may interfere with safety or efficacy assessments during the study

7. No immunosuppressants

8. No use of systemic or intra-articular corticosteroids

• No human albumin treatment in the 3 months before randomization or throughout the duration of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Research Associates, Inc.	Birmingham	Alabama	United States	35205
2	CORE Orthopaedic Medical Center	Encinitas	California	United States	92024
3	St. Joseph Heritage	Fullerton	California	United States	92835
4	Artemis Institute for Clinical Research	San Diego	California	United States	92103
5	Westlake Medical Research	Thousand Oaks	California	United States	91360
6	Drug Studies America	Marietta	Georgia	United States	30060
7	Healthcare Research Netword	Blue Island	Illinois	United States	60406
8	Heartland Research Associates	Wichita	Kansas	United States	67207
9	Arthritis Treatment Center	Frederick	Maryland	United States	21702
10	Healthcare Network Research	Hazelwood	Missouri	United States	63042
11	Coastal Carolina Center at Lowcountry Orthopaedics	North Charleston	South Carolina	United States	29406
12	Tekton Research	Austin	Texas	United States	78745
13	Northwest Clinical Research Center	Bellevue	Washington	United States	98007

Sponsors and Collaborators

• Ampio Pharmaceuticals. Inc.

Investigators

• Study Director: Howard Levy, MD, Ampio Pharmaceuticals. Inc.

Study Documents (Full-Text)

• Study Protocol - Nov 9, 2017
• Statistical Analysis Plan - Nov 14, 2017

More Information

Publications

None provided.

• Responsible Party: Ampio Pharmaceuticals. Inc.
• ClinicalTrials.gov Identifier: NCT03182686
• Other Study ID Numbers: AP-003-C
• First Posted: Jun 9, 2017
• Last Update Posted: Aug 9, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ampio Pharmaceuticals. Inc.: osteoarthritis; osteoarthritis of the knee; OA; OAK; Kellgren Lawrence (KL)
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee

Study Results

Participant Flow

Arm/Group Title	Ampion 4 mL Dose	Saline 4 mL Dose
Arm/Group Description	Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% Human Serum Albumin (HSA)), solution, 4 mL, single intra-articular injection Ampion: Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% HSA)	Saline, solution, 4 mL, single intra-articular injection Saline: 0.9% sodium chloride
Period Title: Overall Study
STARTED	144	24
COMPLETED	137	24
NOT COMPLETED	7	0

Baseline Characteristics

Arm/Group Title	Ampion 4 mL Dose	Saline 4 mL Dose	Total
Arm/Group Description	Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% Human Serum Albumin (HSA)), solution, 4 mL, single intra-articular injection Ampion: Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% HSA)	Saline, solution, 4 mL, single intra-articular injection Saline: 0.9% sodium chloride	Total of all reporting groups
Overall Participants	144	24	168
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.74 (9.63)	64.04 (6.25)	62.92 (9.22)
Sex: Female, Male (Count of Participants)
Female	76 52.8%	12 50%	88 52.4%
Male	68 47.2%	12 50%	80 47.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 3.5%	1 4.2%	6 3.6%
Not Hispanic or Latino	139 96.5%	23 95.8%	162 96.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	0 0%	1 0.6%
Asian	3 2.1%	1 4.2%	4 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	27 18.8%	6 25%	33 19.6%
White	111 77.1%	16 66.7%	127 75.6%
More than one race	2 1.4%	1 4.2%	3 1.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	144 100%	24 100%	168 100%
WOMAC Pain (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	2.5 (0.56)	2.4 (0.45)	2.5 (0.55)
WOMAC Function (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	2.6 (0.53)	2.5 (0.53)	2.6 (0.53)
Patient's Global Assessment (PGA) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	2.8 (0.80)	2.7 (0.75)	2.8 (0.79)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Classified as Responders
Description	Using the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria of WOMAC A Pain subscore, WOMAC C Function subscore, and PGA as composite endpoints. A patient in this study will be considered a responder for the purpose of efficacy analysis if the following criteria are met: (1) demonstration of ≥ 50% improvement AND a 1.0-unit change in pain OR 1.0-unit change in function OR If the patient does not meet this criterion, then the patient must demonstrate at least 2 of the following: Improvement in pain (WOMAC A) ≥20% and a 0.5 point absolute change in pain from Baseline on the 5-point Likert scale Improvement in function (WOMAC C) ≥20% and a 0.5 point absolute change in function from Baseline on the 5-point Likert scale Improvement in patient global assessment (PGA) ≥20% and a 0.5 point absolute change in function from Baseline on the 5-point Likert scale
Time Frame	Determined from Baseline to 12 Weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT)

Arm/Group Title	Ampion 4 mL Dose	Saline 4 mL Dose
Arm/Group Description	Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% Human Serum Albumin (HSA)), solution, 4 mL, single intra-articular injection Ampion: Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% HSA)	Saline, solution, 4 mL, single intra-articular injection Saline: 0.9% sodium chloride
Measure Participants	144	24
Count of Participants [Participants]	102 70.8%	15 62.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ampion 4 mL Dose, Saline 4 mL Dose
	Comments	H0:π ≤ π0 versus HA:π > π0 Where π0 is the hypothesized clinically significant value for the proportion of responders. The value will be 30% in this study. This test will be tested using an exact binomial test. That is, given the sample size of n, the number of responders X, and the value of π0 =0.30, then probability that X or more events would be observed will be calculated as the p-value. Since this is a one-sided test, the alpha level will be 0.025.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	12 Weeks
Adverse Event Reporting Description	Patients will be followed for the occurrence of Adverse Events until 12 weeks after the first dose of study medication
Arm/Group Title	Ampion 4 mL Dose		Saline 4 mL Dose
Arm/Group Description	Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% Human Serum Albumin (HSA)), solution, 4 mL, single intra-articular injection Ampion: Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% HSA)		Saline, solution, 4 mL, single intra-articular injection Saline: 0.9% sodium chloride
All Cause Mortality
	Ampion 4 mL Dose		Saline 4 mL Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/144 (0%)		0/24 (0%)
Serious Adverse Events
	Ampion 4 mL Dose		Saline 4 mL Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/144 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Ampion 4 mL Dose		Saline 4 mL Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/144 (36.1%)		8/24 (33.3%)
Gastrointestinal disorders
Nausea	2/144 (1.4%)		0/24 (0%)
General disorders
Influenza-like illness	0/144 (0%)		1/24 (4.2%)
Injection site joint pain	0/144 (0%)		1/24 (4.2%)
Infections and infestations
Upper respiratory tract infection	1/144 (0.7%)		1/24 (4.2%)
Viral upper respiratory tract infection	4/144 (2.8%)		0/24 (0%)
Injury, poisoning and procedural complications
Fall	2/144 (1.4%)		0/24 (0%)
Procedural pain	2/144 (1.4%)		0/24 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/144 (13.2%)		2/24 (8.3%)
Arthropathy	2/144 (1.4%)		0/24 (0%)
Joint stiffness	3/144 (2.1%)		2/24 (8.3%)
Joint swelling	4/144 (2.8%)		0/24 (0%)
Osteoarthritis	2/144 (1.4%)		0/24 (0%)
Pain in extremity	2/144 (1.4%)		0/24 (0%)
Synovial cyst	2/144 (1.4%)		0/24 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	3/144 (2.1%)		1/24 (4.2%)
Nervous system disorders
Headache	4/144 (2.8%)		0/24 (0%)

Limitations/Caveats

[Not Specified]

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.