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

• ClinicalTrials.gov Identifier: NCT03182686
• Recruitment Status: Completed
• First Posted: June 9, 2017
• Last Update Posted: June 20, 2019
• Sponsor: Ampio Pharmaceuticals. Inc.
• Information provided by (Responsible Party): Ampio Pharmaceuticals. Inc.

Tracking Information

• First Submitted Date: June 6, 2017
• First Posted Date: June 9, 2017
• Last Update Posted Date: June 20, 2019
• Actual Study Start Date: June 19, 2017
• Actual Primary Completion Date: December 5, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 19, 2017)

Evaluate responder status using OMERACT-OARSI using WOMAC A subscore, WOMAC C subscore, and PGA as composite endpoints [ Time Frame: Week 12 ]

A patient in this study will be considered a responder for the purpose of efficacy analysis if the following criteria is met.

1. The patient has a percent improvement in pain (WOMAC A) of ≥50% and an absolute change in pain from baseline of ≥ 1 point on the 5-point Likert scale or the patient has a percent improvement in function (WOMAC C) ≥50% and an absolute change in function from baseline of ≥1 point on the 5-point Likert scale. If the patient does not meet this criterion, then
2. The patient demonstrates improvement in 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 PGA from Baseline on the 5-point Likert scale

Original Primary Outcome Measures (submitted: June 8, 2017)

Evaluate responder status (improvement of >30%) of WOMAC A pain subscore, WOMAC C function subscore, and PGA as composite endpoints (OMERACT-OARSI Scenario D) [ Time Frame: Week 12 ]

Evaluate a single 4 mL Ampion intra-articular injection at Baseline in improving knee pain at Week 12 using the OMERACT-OARSI scenario D criteria (using the WOMAC 3.1 Index and PGA as assessments)

Current Secondary Outcome Measures (submitted: December 19, 2017)

• Evaluate improvement of the composite endpoint of WOMAC A and WOMAC C [ Time Frame: Week 12 ]
  Evaluate improvement in the composite endpoint of pain and function (WOMAC A and C) from Baseline to Week 12
• Evaluate improvement in PGA [ Time Frame: Week 12 ]
  Evaluate improvement in PGA from Baseline to Week 12
• Evaluate improvement in the composite endpoint of pain and function (WOMAC A and C) compared to saline from all single-injection Ampion studies [ Time Frame: Week 12 ]
  Evaluate improvement in the composite endpoint of pain and function (WOMAC A and C) compared to saline from all single-injection Ampion studies from Baseline to Week 12

Original Secondary Outcome Measures (submitted: June 8, 2017)

• Percent Reduction in WOMAC A pain subscore [ Time Frame: Week 12 ]
  Percent change in WOMAC pain subscore (WOMAC A) from Baseline (Day 0) to Week 12 using the WOMAC osteoarthritis Index, 5-point Likert Scale
• Safety: Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Week 12 ]
  Incidence and severity of treatment-emergent adverse events (TEAEs)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

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 OMERACT-OARSI (using the WOMAC 3.1 Index and PGA as assessments).

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Osteoarthritis, Knee
• Knee Osteoarthritis
• Knee Arthritis
• Knee Pain Chronic

Intervention

• Biological: Ampion
  Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% HSA)
• Other: Saline
  0.9% sodium chloride

Study Arms

• Experimental: Ampion
  Ampion (<5 kilodalton (kDa) ultrafiltrate of 5% Human Serum Albumin (HSA)), solution, 4 mL, single intra-articular injection
  Intervention: Biological: Ampion
• Saline
  Saline, solution, 4 mL, single intra-articular injection
  Intervention: Other: Saline

• Publications *: Salottolo K, Cole B, Bar-Or D. Intra-articular injection of the anti-inflammatory compound LMWF-5A in adults with severe osteoarthritis: a double-blind prospective randomized controlled multi-center safety and efficacy trial. Patient Saf Surg. 2018 Jun 18;12:11. doi: 10.1186/s13037-018-0158-0. eCollection 2018.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 19, 2017): 168
• Original Estimated Enrollment (submitted: June 8, 2017): 171
• Actual Study Completion Date: December 7, 2017
• Actual Primary Completion Date: December 5, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 4) 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03182686
• Other Study ID Numbers: AP-003-C
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Ampio Pharmaceuticals. Inc.
• Study Sponsor: Ampio Pharmaceuticals. Inc.
• Collaborators: Not Provided

Investigators

• Study Director: David Bar-Or, MD; Ampio Pharmaceuticals. Inc.
• Study Director: Holly Mitzel; Ampio Pharmaceuticals. Inc.

• PRS Account: Ampio Pharmaceuticals. Inc.
• Verification Date: June 2019