Affinity Prospective Diabetic Foot Trial Crossover Group

This study is an extension of the randomized controlled trial NT-DFU-AFF-01 in which subjects
were randomized to SOC for 12 weeks or SOC and fresh hypothermically stored human amniotic
membrane (Affinity; fHSAM) for 12 weeks to determine if addition of fHSAM to SOC results in
faster healing of Wagner grade 1 and 2 DFUs compared to SOC alone.

At 6 weeks, patients from this RCT (NT-DFU-AFF-01) with study DFUs that have not been reduced
in area by at least 40% will be exited from the study and considered treatment failures. This
group (Group 2C) will constitute the active population in this single arm study
(NT-DFU-AFF-02). Study wounds will receive up to 12 weeks of continuing SOC and fHSAM.

The standard of care therapy in this study is offloading of the DFU, appropriate sharp or
surgical debridement, and aggressive infection management with the use of appropriate
dressings (defined later in the protocol). A number of offloading systems are commercially
available. The choice of offloading will be at the discretion of the principal investigator
but should be total contact casting, fixed ankle walker boot, or equivalent device to the
fixed ankle walker boot.

The Screening Phase (1 day) consists of a series of screening assessments designed to
determine eligibility followed by, for those who meet the eligibility criteria (described in
more detail below), treatment. At the Screening Visit (S1), written informed consent from the
subject will be obtained by the Investigator or suitably qualified designee before the
performance of any other protocol-specific procedure. The Screening Period is designed to
determine whether subjects are eligible to proceed to the Treatment Phase of the study.

The Treatment Phase (12 Weeks) begins on the same day as the screening visit. During the
Treatment Phase, subjects will be evaluated on a weekly basis. Efficacy evaluations each week
will include Investigator assessment of ulcer healing and measurements of ulcer size using
digital photographic planimetry. Safety evaluations during the Treatment Phase will consist
of adverse event assessments at each visit.

Subjects whose ulcers do not achieve closure at 12 weeks or who experience an amputation will
be deemed treatment failures.

Inclusion Criteria:

1. A percentage area reduction of less than 40% after having received 6 weeks of
treatment with SOC in the NT-DFU-01 trial.

2. Subject understands and is willing to participate in the clinical study and can comply
with weekly visits and the follow-up regimen.

3. Subject has read and signed the IRB/IEC approved Informed Consent Form.

4. Females of childbearing potential must be willing to use acceptable methods of
contraception (birth control pills, barriers, or abstinence).

5. At least 18 years old.

Exclusion Criteria:

1. Failure to complete 6 weeks of SOC in the original NT-DFU-01 study

2. Any AE or SAE that occurred during the NT-DFU-01 study, which, in the opinion of the
investigator would preclude the subject successfully having Affinity applied for up to
12 weeks.

3. Subject is unlikely to complete a regimen of Affinity and SOC for up to 12 weeks due
to personal reasons.

4. Subject is pregnant or breast feeding.

5. Osteomyelitis or bone infection of the affected foot as assessed by X-ray.