Study of Intra-articular Injections vs Placebo in Patients With Pain From Osteoarthritis of the Knee

NCT01887678 | Completed Phase 3 Results

• 1 other identifier: C1301
• Study Type: interventional
• Target: 287
• Locations: 1 country
• Sites: 30

Brief Summary

The aim of this study is to evaluate the effectiveness and safety of a combined Traumeel® / Zeel® injection against placebo (saline) in patients with moderate-to-severe pain associated with osteoarthritis of the knee.

Conditions

Osteoarthritis, Knee

Outcome Measures

Primary Outcomes (1)

• Change in Knee Pain as Measured by the WOMAC Osteoarthritis (OA) Index Pain Subscale (Section A, Items #1-5) Measured by 100 mm VAS

  Changes of the target (treated) knee were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC OA) whereby patients self-assessed 24 parameters on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS) where 0 corresponded to 'None' and 100 to 'Extreme'. To assess pain, scores from WOMAC Section A, items 1 to 5 are averaged to yield the Pain Subscale total score. At Study Days 1, 8 and 15 where injections were administered, this was to be done before injection. A two-sided test of equality of the study drug (Traumeel®-Zeel®) and Placebo at level 0.05 was computed using an analysis of covariance (ANCOVA) model with treatment group as qualitative factor and the corresponding Baseline value of the primary efficacy variable as a covariate. The test decision was based on the (two-sided) p-value for the corresponding test of no treatment difference.

  from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

Secondary Outcomes (14)

• Pain Subscore (WOMAC Section A, Items #1-5) Measured by 100 mm VAS

  from Baseline to post-Baseline visits except End of Study Visit (up to day 105)

• Stiffness Subscore (WOMAC Section B, Items #6-7) Measured by 100 mm VAS

  from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

• Physical Function Bubscore (WOMAC Section C, Items #8-24) Recorded on 100 mm VAS

  from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

• Total WOMAC Score (All Subscales) Recorded on 100 mm VAS

  from Baseline (Day 1, predose) to End of Study Visit (up to Day 119)

• Patient Global Assessment (PGA)

  from Baseline (Day 1, predose)

Other Outcomes (4)

• Serious Adverse Events

  Start of Lead-In period until individual study end, up to 16 weeks.

• Each Adverse Event (AE)

  Starting at Visit 2/ Start of Lead-In period (Day 7 up to day 119)

• Incidence of Treatment Emergent Adverse Events (TEAEs)

  during the treatment period and follow up period (Days 11 to 119)

Study Arms (2)

Traumeel® / Zeel® Injectable Solution

EXPERIMENTAL

Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one intra articular (IA) injection) on treatment days 1, 8 and 15.

Drug: Traumeel® / Zeel® Injectable Solution

Placebo injectable solution

PLACEBO COMPARATOR

Injection volume of placebo is 4.2 mL as well (taken from the 10.0 mL vial by unblinded staff member, rest to be kept for drug accountability)

Drug: Placebo

Interventions

Traumeel® / Zeel® Injectable Solution DRUG

Injection volume is 4.2 mL for active study medication (2.0 mL Zeel plus 2.2 mL Traumeel in one IA injection) on treatment days 1, 8 and 15.

Also known as: Traumeel, Zeel

Traumeel® / Zeel® Injectable Solution

Placebo DRUG

Placebo is an injection of Saline

Also known as: Saline

Placebo injectable solution

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Osteoarthritis (OA) of the knee by American College of Rheumatology criteria
• Men or women between 45-80 years of age.
• Have documented diagnosis of primary OA of the target knee based on clinical and radiographic criteria (Kellgren-Lawrence Numerical Grading System of Grade 2-3) in the tibial-femoral compartment of the target knee confirmed by standard post-anterior weightbearing X-ray of the knee in full extension taken \</= 6 months prior to Visit 1.
• Currently taking an Nonsteroidal anti-inflammatory drug (NSAID), or acetaminophen on a regular basis (4-7 days/ week) over last 2 weeks prior to Visit 1 and has experienced amelioration of pain on these medications.
• Must have a 50-foot walk test pain score of less than 40 mm on a 100 mm VAS in the target knee at screening
• Pain in the non-target (contralateral) knee must not be greater than 30 mm on a 100 mm VAS on 50-foot walk test, and the target knee must be more symptomatic.
• Willingness to stop all OA treatments.
• Fully informed of the risks of entering the study and willing to provide written consent to enter the study.
• Able to understand and be willing to comply with all study requirements, particularly the weekly injection regimen for administration of study drug.
• Primary complaint is pain immediately following an unassisted 50-foot walk. They must show:
• moderate to severe pain score in the target knee as demonstrated by 40 - 90 mm recorded on a 100 mm VAS, and
• mm increase in pain from their screening visit pain score (a "flare")
• pain in the non-target (contralateral) knee must \</= 30 mm on a 100 mm VAS

You may not qualify if:

• Known hypersensitivity or allergy to any of the components of Traumeel or Zeel
• Known hypersensitivity or allergy to acetaminophen.
• Has body mass index (BMI) \>38 kg/m2.
• Avoidance of, or aversion to, nonprescription medications.
• Clinical symptoms of meniscal instability or significant valgus/ varus that requires corrective osteotomy
• Any major injury or surgery to the target knee in the prior 12 months.
• One or a combination of the following co-morbidities:
• other inflammatory arthropathies, gout or pseudogout within previous 6 months
• avascular necrosis
• severe bone or joint deformity in target knee
• osteonecrosis of either knee
• fibromyalgia
• pes anserine bursitis
• lumbar radiculopathy with referred pain to either knee
• neurogenic or vascular claudication

Sponsors & Collaborators

• Biologische Heilmittel Heel GmbH: lead

Study Sites (30)

Clinical Research Advantage - Arizona II

Phoenix, Arizona, 85050, United States

Location

Tucson Orthopaedic Institute

Tucson, Arizona, 85712, United States

Location

Universal BioPharma Research Inc.

Dinuba, California, 93618, United States

Location

Providence Clinical Research

North Hollywood, California, 91606, United States

Location

Hans Richard Barthel, M.D., Inc.

Santa Barbara, California, 93108, United States

Location

Westlake Medical Research

Westlake Village, California, 91361, United States

Location

Radiant Research Inc. - Denver

Denver, Colorado, 80239, United States

Location

Riverside Clinical Research

Edgewater, Florida, 32132, United States

Location

AppleMed Research, Inc.

Miami, Florida, 33155, United States

Location

Radiant Research Inc.

Pinellas Park, Florida, 33781, United States

Location

Injury Care Medical Center

Boise, Idaho, 83713, United States

Location

Global Scientific Innovations

Evansville, Indiana, 47714, United States

Location

Sundance Clinical Research, LLC

St Louis, Missouri, 63141, United States

Location

Manhattan Medical Research

New York, New York, 10016, United States

Location

Research Across America - NY

New York, New York, 10022, United States

Location

PMG Cary Medical Research

Cary, North Carolina, 27518, United States

Location

New Hope Clinical Research

Charlotte, North Carolina, 28204, United States

Location

PMG Research of Charlotte

Charlotte, North Carolina, 28209, United States

Location

PMG Research of Raleigh

Raleigh, North Carolina, 27609, United States

Location

PMG Research of Salisbury

Salisbury, North Carolina, 28144, United States

Location

Radiant Research Inc. - Akron

Akron, Ohio, 44311, United States

Location

Sterling Research Group, Ltd

Cincinnati, Ohio, 45246, United States

Location

Clinical Inquest Center Ltd.

Dayton, Ohio, 45431, United States

Location

Hillcrest Clinical Research

Oklahoma City, Oklahoma, 73119, United States

Location

Blair Orthopedic Associates, Inc.

Altoona, Pennsylvania, 16602, United States

Location

Clinical Research Solutions

Franklin, Tennessee, 37064, United States

Location

PMG Research of Knoxville

Knoxville, Tennessee, 37912, United States

Location

PMG Research of Knoxville

Knoxville, Tennessee, 37938, United States

Location

Clinical Research Solutions

Smyrna, Tennessee, 37167, United States

Location

Radiant Research Inc. - Salt Lake City

Salt Lake City, Utah, 84123, United States

Location

Related Publications (1)

• Lozada CJ, del Rio E, Reitberg DP, Smith RA, Kahn CB, Moskowitz RW. A double-blind, randomized, saline-controlled study of the efficacy and safety of co-administered intra-articular injections of Tr14 and Ze14 for treatment of painful osteoarthritis of the knee: The MOZArT trial. Eur J Integr Med 2017;13:54-63. DOI: 10.1016/j.eujim.2017.07.005;

  RESULT

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Traumeel S; Sodium Chloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Christine Frank, PhD, Global Clinical Project Manager
• Organization: Biologische Heilmittel Heel GmbH

christine.frank@heel.com

+49 7221 501 3188

Study Officials

• Nebojsa Skrepnik, MD

  Tucson Orthopaedic Institute

  PRINCIPAL INVESTIGATOR

• Royal Anspach, MD

  Clinical Research Advantage - Arizona II

  PRINCIPAL INVESTIGATOR

• Hans Barthel, MD

  Hans Richard Barthel, M.D., Inc.

  PRINCIPAL INVESTIGATOR

• Shariar Cohen-Gadol, MD

  Westlake Medical Research

  PRINCIPAL INVESTIGATOR

• David Bolshoun, MD

  Radiant Research Inc. - Denver

  PRINCIPAL INVESTIGATOR

• Linda Murray, DO

  Radiant Research Inc

  PRINCIPAL INVESTIGATOR

• Susan Hole, DO

  Riverside Clinical Research

  PRINCIPAL INVESTIGATOR

• Agustin Latorre, MD

  AppleMed Research, Inc.

  PRINCIPAL INVESTIGATOR

• Richard Radnovich, DO

  Injury Care Medical Center

  PRINCIPAL INVESTIGATOR

• Moges Sisay, MD

  Global Scientific Innovations

  PRINCIPAL INVESTIGATOR

• Larkin T Wadsworth, MD

  Sundance Clinical Research, LLC

  PRINCIPAL INVESTIGATOR

• Kurian Abraham, MD

  New Hope Clinical Research

  PRINCIPAL INVESTIGATOR

• Rakesh Patel, MD

  PMG Research of Salisbury

  PRINCIPAL INVESTIGATOR

• George Raad, MD

  PMG Research of Charlotte

  PRINCIPAL INVESTIGATOR

• Martin VanCleeff, MD

  PMG Cary Medical Research

  PRINCIPAL INVESTIGATOR

• John Rubino, MD

  PMG Research of Raleigh

  PRINCIPAL INVESTIGATOR

• Howard R Adelglass, MD

  Research Across America - NY

  PRINCIPAL INVESTIGATOR

• Louis Re, MD

  Manhattan Medical Research

  PRINCIPAL INVESTIGATOR

• Daniel Whitmer, MD

  Clinical Inquest Center Ltd.

  PRINCIPAL INVESTIGATOR

• Jeffrey Klein, MD

  Radiant Research Inc. - Akron

  PRINCIPAL INVESTIGATOR

• Rakesh Davit, MD

  Sterling Research Group, Ltd.

  PRINCIPAL INVESTIGATOR

• Glenn Smith, DO

  Hillcrest Clinical Research

  PRINCIPAL INVESTIGATOR

• Shawn Saylor, DO

  Blair Orthopedic Associates, Inc

  PRINCIPAL INVESTIGATOR

• Alex Slandzicki, MD

  Clinical Research Solutions

  PRINCIPAL INVESTIGATOR

• Sadia Dar, MD

  Clinical Research Solutions

  PRINCIPAL INVESTIGATOR

• Rickey Manning, MD

  PMG Research of Knoxville

  PRINCIPAL INVESTIGATOR

• Paul Wakefield, MD

  PMG Research of Knoxville

  PRINCIPAL INVESTIGATOR

• Michael R Adams, MD

  Radiant Research Inc. - Salt Lake City

  PRINCIPAL INVESTIGATOR

• Teresa Sligh, MD

  Providence Clinical Research

  PRINCIPAL INVESTIGATOR

• David. Cardona, MD

  Universal BioPharma Research Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: June 27, 2013
• Study Start: June 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: April 2, 2018
• Results First Posted: March 20, 2015

Record last verified: 2018-03

Locations

US (30)