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Compound monograph · evidence extract

AOD-9604 in knee osteoarthritis with obesity — evidence extract

The Institute's graded assessment of AOD-9604 for knee osteoarthritis with obesity, with the contributing trials and the domain-by-domain certainty reasoning.

Document identifier
CEI-MN-028/EV-KNEE-OA
Series
Evidence extract
Version
1.0
Published
17 Sep 2025
Last reviewed
17 Sep 2025
Next review
17 Sep 2027
Identifier
10.71829/cei.mono.28
Certainty
Low
Cycle
2025 Q3

§1Evidence extract: Knee osteoarthritis with obesity

§1.1Question and anchor outcome

Population
Degenerative joint disease of the knee with radiographic or symptomatic confirmation, occurring with obesity as a mechanical and inflammatory contributor.
Intervention
AOD-9604, oral in the clinical programme; subcutaneous in research contexts
Comparator
As used in each contributing trial; reported per trial rather than pooled across comparator types
Anchor outcome
WOMAC pain subscale

Additional outcomes the Institute extracts for this indication: Physical function score; Analgesic use; Progression to arthroplasty.

§1.2Contributing trials

Table 1. Trials contributing to the assessment of AOD-9604 in knee osteoarthritis with obesity.

TrialPhaseDesignRandomisedDurationYear
AOD-OA-PH22Randomised, double-blind, placebo-controlled12 weeks2015

§1.3Certainty assessment

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasno downgradeInconsistencyno downgradeIndirectnessdowngrade one levelImprecisionno downgradePublication biasdowngrade one levelTotal downgrading: 2 levelsLow certainty
Figure 2. Domain-by-domain certainty assessment for AOD-9604 in knee osteoarthritis with obesity. The starting rating for a body of randomised evidence is high; each serious concern reduces it by one level and each very serious concern by two.

Table 2. Reasoning recorded against each certainty domain.

DomainRatingReasoning
Risk of biasNo concernNo serious concern identified in this domain.
InconsistencyNo concernNo serious concern identified in this domain.
IndirectnessSeriousAn outcome that would answer the question was not measured in any contributing trial.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasSeriousRegistered trials without posted results were identified for this question.
Overall rating: Low certainty. Confidence in the effect estimate is limited. The true effect may be substantially different from the estimate.

§1.4What this extract does not establish

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. Heffernan M, Summers RJ, Thorburn A, Ogru E, Gianello R, Jiang WJ, Ng FM. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and β3-AR knock-out mice. Endocrinology 2001;142(12):5182–5189. doi:10.1210/endo.142.12.8522 · PMID 11713213
  2. Thevis M, Thomas A, Schänzer W. Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions. Expert Review of Proteomics 2019;11(6):663–673. doi:10.1586/14789450.2014.965158
  3. D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.

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